( Shingles)

Shingles is a skin rash caused by the same virus that causes chickenpox. The virus responsible for these conditions is called the Varicella zoster virus (VZV). After an individual has chickenpox, this virus lives in the nervous system and is never fully cleared from the body.

Under certain circumstances, such as emotional stress, immune deficiency (from AIDS or chemotherapy), or with cancer, the virus reactivates causing shingles. In most cases, however, a cause for the reactivation of the virus is never found. Anyone who has ever had chickenpox is at risk for the development of shingles, although it occurs most commonly in people over the age of 60.

The herpes virus that causes shingles and chickenpox is not the same as the herpes virus that causes genital herpes (which can be sexually transmitted) and herpes mouth sores. Shingles is medically termed Herpes zoster.

Causes : Herpes zoster, or shingles, is caused by the same virus that causes chickenpox. After an episode of chickenpox, the virus becomes dormant in the body. Herpes zoster occurs as a result of the virus re-emerging after many years.

The cause of the re-activation is usually unknown, but seems to be linked to aging, stress, or an impaired immune system. Often only one attack occurs, without recurrence.

If an adult or child is exposed to the herpes zoster virus and has not had chickenpox as a child or received the chickenpox vaccine, a severe case of chickenpox may develop, rather than shingles.

After infection with chickenpox, the virus resides in a non-active state in the nerve tracts that emerge from the spine. When it is re-activated, it spreads along the nerve tract, first causing pain or a burning sensation.

The typical rash appears in 2 to 3 days, after the virus has reached the skin. It consists of red patches of skin with small blisters (vesicles) that look very similar to early chickenpox. The rash often increases over the next 3 to 5 days. Then, the blisters break, forming small ulcers that begin to dry and form crusts. The crusts fall off in 2 to 3 weeks, leaving behind pink healing skin.

Lesions typically appear along a single dermatome (the body area served by a single spinal nerve) and are only on one side of the body (unilateral). The trunk is most often affected, showing a rectangular belt of rash from the spine around one side of the chest to the breastbone (sternum).

Lesions may also occur on the neck or face, particularly along the trigeminal nerve in the face. The trigeminal has three branches that go to the forehead, the mid-face, and the lower face. Which branch is involved determines where on the face the skin lesions will be.

Trigeminal nerve involvement may include lesions in the mouth or eye. Eye lesions may lead to permanent blindness if not treated with emergency medical care.

Involvement of the facial nerve may cause Ramsay Hunt syndrome with facial paralysis, hearing loss, loss of taste in half of the tongue and skin lesions around the ear and ear canal. Shingles may, on occasion, involve the genitals or upper leg.

Shingles may be complicated by a condition known as post-herpetic neuralgia. This is persistence of pain in the area where the shingles occurred that may last from months to years following the initial episode. This pain can be severe enough to be incapacitating. The elderly are at higher risk for this complication.

Herpes zoster can be contagious through direct contact in an individual who has not had chickenpox, and therefore has no immunity. Herpes zoster may affect any age group, but it is much more common in adults over 60 years old, in children who had chickenpox before the age of one year, and in individuals whose immune system is weakened. The disorder is common, with about 600,000 to one million cases in the U.S. per year.

Most commonly, an outbreak of shingles is localized and involves only one dermatome. Widespread or recurrent shingles may indicate an underlying problem with the immune system such as leukemia, Hodgkin’s disease and other cancers, atopic dermatitis, HIV infection, or AIDS. People with suppressed immune systems due to organ transplant or treatment for cancer are also at risk.

Symptoms: The earliest symptoms of herpes zoster, which include headache, fever, and malaise, are nonspecific, and may result in an incorrect diagnosis. These symptoms are commonly followed by sensations of burning pain, itching, hyperesthesia, or paresthesia (sensitivity to heat, cold, light or touch). The pain may be extreme in the affected dermatome, with sensations that are often described as stinging, tingling, aching, numbing or throbbing, and can be interspersed with quick stabs of agonizing pain. In most cases, after 1–2 days (but sometimes as long as 3 weeks) the initial phase is followed by the appearance of the characteristic skin rash. The pain and rash most commonly occurs on the torso, but can appear on the face, eyes or other parts of the body. At first, the rash appears similar to the first appearance of hives; however, unlike hives, herpes zoster causes skin changes limited to a dermatome (an area of skin supplied by one spinal nerve), normally resulting in a stripe or belt-like pattern that is limited to one side of the body and does not cross the midline. Zoster sine herpete describes a patient who has all of the symptoms of herpes zoster except this characteristic rash.

Later, the rash becomes vesicular, forming small blisters filled with a serous exudate, as the fever and general malaise continue. The painful vesicles eventually become cloudy or darkened as they fill with blood, crust over within seven to ten days, and usually the crusts fall off and the skin heals: but sometimes after severe blistering, scarring and discolored skin remain.

Herpes zoster may have additional symptoms, depending on the dermatome involved. Herpes zoster ophthalmicus involves the orbit of the eye and occurs in approximately 10–25% of cases. It is caused by the virus reactivating in the ophthalmic division of the trigeminal nerve. In a few patients, symptoms may include conjunctivitis, keratitis, uveitis, and optic nerve palsies that can sometimes cause chronic ocular inflammation, loss of vision, and debilitating pain.[13] Herpes zoster oticus, also known as Ramsay Hunt syndrome type II, involves the ear. It is thought to result from the virus spreading from the facial nerve to the vestibulocochlear nerve. Symptoms include hearing loss and vertigo (rotational dizziness).

Diagnosis:

If the rash has appeared, identifying this disease (making a differential diagnosis) only requires a visual examination, since very few diseases produce a rash in a dermatomal pattern (see map). However, herpes simplex virus (HSV) can occasionally produce a rash in such a pattern. The Tsanck smear is helpful for diagnosing acute infection with a herpes virus, but does not distinguish between HSV and VZV.

When the rash is absent (early or late in the disease, or in the case of zoster sine herpete), herpes zoster can be difficult to diagnose. Apart from the rash, most symptoms can occur also in other conditions.

Laboratory tests are available to diagnose herpes zoster. The most popular test detects VZV-specific IgM antibody in blood; this only appears during chickenpox or herpes zoster and not while the virus is dormant.[16] In larger laboratories, lymph collected from a blister is tested by the polymerase chain reaction for VZV DNA, or examined with an electron microscope for virus particles.

In a recent study, samples of lesions on the skin, eyes, and lung from 182 patients with presumed herpes simplex or herpes zoster were tested with real-time PCR or with viral culture.[18] In this comparison, viral culture detected VZV with only a 14.3% sensitivity, although the test was highly specific (specificity=100%). By comparison, real-time PCR resulted in 100% sensitivity and specificity. Overall testing for herpes simplex and herpes zoster using PCR showed a 60.4% improvement over viral culture.

Pathophysiology

Progression of herpes zoster. A cluster of small bumps  turns into blisters . The blisters fill with lymph, break open , crust over , and finally disappear. Postherpetic neuralgia can sometimes occur due to nerve damage.

Progression of herpes zoster. A cluster of small bumps  turns into blisters . The blisters fill with lymph, break open , crust over , and finally disappear. Postherpetic neuralgia can sometimes occur due to nerve damage .

The causative agent for herpes zoster is varicella zoster virus (VZV), a double-stranded DNA virus related to the Herpes simplex virus group. Most people are infected with this virus as children, and suffer from an episode of chickenpox. The immune system eventually eliminates the virus from most locations, but it remains dormant (or latent) in the ganglia adjacent to the spinal cord (called the dorsal root ganglion) or the ganglion semilunare (ganglion Gasseri) in the base of the skull. However, repeated attacks of herpes zoster are rare, and it is extremely rare for patients to suffer more than three recurrences.

Herpes zoster occurs only in people who have had chickenpox, and although it can occur at any age, the vast majority of sufferers are more than 50 years old. The disease results from the virus reactivating in a single sensory ganglion. In contrast to Herpes simplex virus the latency of VZV is poorly understood. The virus has not been recovered from human nerve cells by cell culture and the location and structure of the viral DNA is not known. Virus-specific proteins continue to be made by the infected cells during the latent period, so true latency, as opposed to a chronic low-level infection, has not been proven. Although VZV has been detected in autopsies of nervous tissue, there are no methods to find dormant virus in the ganglia in living people.

 Unless the immune system is compromised, it suppresses reactivation of the virus and prevents herpes zoster. Why this suppression sometimes fails is poorly understood, but herpes zoster is more likely to occur in people whose immune system is impaired due to aging, immunosuppressive therapy, psychological stress, or other factors.] Upon reactivation, the virus replicates in the nerve cells, and virions are shed from the cells and carried down the axons to the area of skin served by that ganglion. In the skin, the virus causes local inflammation and blisters. The short and long-term pain caused by herpes zoster comes from the widespread growth of the virus in the infected nerves, which causes inflammation.

The symptoms of herpes zoster cannot be transmitted to another person.[25] However, during the blister phase, direct contact with the rash can spread VZV to a person who has no immunity to the virus. This newly-infected individual may then develop chickenpox, but they will not immediately develop shingles. Once the rash has developed crusts, a person is extremely contagious. A person is also not infectious before blisters appear, or during postherpetic neuralgia (pain after the rash is gone). The person is no longer contagious after the virus has disappeared.[10]

Prognosis: The rash and pain usually subside within three to five weeks, but about one in five patients develops a painful condition called postherpetic neuralgia, which is often difficult to manage. In some patients, herpes zoster can reactivate presenting as zoster sine herpete: pain radiating along the path of a single spinal nerve (a dermatomal distribution), but without an accompanying rash. This condition may involve complications that affect several levels of the nervous system and cause multiple cranial neuropathies, polyneuritis, myelitis, or aseptic meningitis. Other serious effects that may occur in some cases include partial facial paralysis (usually temporary), ear damage, or encephalitis. During pregnancy, first infections with VZV, causing chickenpox, may lead to infection of the fetus and complications in the newborn, but chronic infection or reactivation in shingles are not associated with fetal infection.

There is a slightly increased risk of developing cancer after a herpes zoster infection. However, the mechanism is unclear and mortality from cancer did not appear to increase as a direct result of the presence of the virus. Instead, the increased risk may result from the immune suppression that allows the reactivation of the virus.

Treatment:  The aims of treatment are to limit the severity and duration of pain, shorten the duration of a shingles episode, and reduce complications. Symptomatic treatment is often needed for the complication of postherpetic neuralgia.

Antiviral drugs inhibit VZV replication and reduce the severity and duration of herpes zoster with minimal side effects, but do not reliably prevent postherpetic neuralgia. Of these drugs, aciclovir has been the standard treatment, but the new drugs valaciclovir and famciclovir demonstrate similar or superior efficacy and good safety and tolerability. The drugs are used both as prophylaxis (for example in AIDS patients) and as therapy during the acute phase. Antiviral treatment is recommended for all immunocompetent individuals with herpes zoster over 50 years old, preferably given within 72 hours of the appearance of the rash. Complications in immunocompromised individuals with herpes zoster may be reduced with intravenous aciclovir. In people who are at a high risk for repeated attacks of shingles, five daily oral doses of aciclovir are usually effective.] Administering gabapentin along with antivirals may offer relief of postherpetic neuralgia.

Patients with mild to moderate pain can be treated with over-the-counter analgesics. Topical lotions containing calamine can be used on the rash or blisters and may be soothing. Occasionally, severe pain may require an opioid medication, such as morphine. Once the lesions have crusted over, capsaicin cream (Zostrix) can be used. Topical lidocaine and nerve blocks may also reduce pain.

Orally administered corticosteroids are frequently used in treatment of the infection, despite clinical trials of this treatment being unconvincing. Nevertheless, one trial studying immunocompetent patients older than 50 years of age with localized herpes zoster, suggested that administration of prednisone with aciclovir improved healing time and quality of life. Upon one-month evaluation, aciclovir with prednisone increased the likelihood of crusting and healing of lesions by about two-fold, when compared to placebo. This trial also evaluated the effects of this drug combination on quality of life at one month, showing that patients had less pain, and were more likely to stop the use of analgesic agents, return to usual activities and have uninterrupted sleep. However, when comparing cessation of herpes zoster-associated pain or post herpetic neuralgia, there was no difference between aciclovir plus prednisone, or simply aciclovir alone. Because of the risks of corticosteroid treatment, it is recommended that this combination of drugs only be used in people more than 50 years of age, due to their greater risk of postherpetic neuralgia.

Treatment for herpes zoster ophthalmicus is similar to standard treatment for herpes zoster at other sites. A recent trial comparing aciclovir with its prodrug, valaciclovir, demonstrated similar efficacies in treating this form of the disease. The significant advantage of valciclovir over aciclovir is its dosing of only 3 times/day (compared with acyclovir’s 5 times/day dosing), which could make it more convenient for patients and improve adherence with therapy.

Prevention:  A live vaccine for VZV exists, marketed as Zostavax. In a 2005 study of 38,000 older adults it prevented half the cases of herpes zoster and reduced the number of cases of postherpetic neuralgia by two-thirds.

(HSV)

Herpes is an infection that is caused by a herpes simplex virus (HSV). Oral herpes causes cold sores around the mouth or face. Genital herpes affects the genitals, buttocks or anal area. Genital herpes is a sexually transmitted disease (STD). You can get it from having sex, even oral sex. The virus can spread even when sores are not present. Mothers can also infect their babies during childbirth.

Some people have no symptoms. Others get sores near the area where the virus has entered the body. They turn into blisters, become itchy and painful, and then heal. The virus can be dangerous in newborn babies or in people with weak immune systems.

Most people have outbreaks several times a year. Over time, you get them less often. Medicines to help your body fight the virus can help lessen symptoms and decrease outbreaks. Correct usage of latex condoms can reduce, but not eliminate, the risk of catching or spreading herpes.

Symptoms: Symptoms vary depending on the stage of the virus, the initial or primary outbreak, and recurrence. Both herpes simplex viruses 1 and 2 produce similar symptoms, but they can differ in severity depending on the site of infection. More than 60% of new HSV-2 infections and about a third of new HSV-1 infections do not produce symptoms.

Skin Eruptions and Pain. The first time a person experiences a herpes simplex outbreak, skin eruptions appear 2 - 12 days after the initial exposure to the virus.

·         The first sign of infection is fluid accumulation (edema) at the infection site, which is quickly followed by small, grouped blisters — the characteristic HSV lesions.

·         These form on an inflamed skin base, which is more visible in dry skin areas.

·         The blisters then dry out and heal rapidly without scarring within 7 - 10 days. Blisters in moist areas heal more slowly than others. The lesions may sometimes itch, but itching decreases as lesions heal.

·         When the crust falls off, the lesions are no longer contagious. (The virus may still be active in nearby tissue, but such persistence is rare.)

·         Once HSV gains entry to a site in the body, the virus can also spread to nearby mucosal areas through nerve cells. This characteristic spreading can cause fairly large infected areas to erupt at some distance from the initial crop of sores.

The primary skin infection with either HSV-1 or HSV-2 lasts up to 2 - 3 weeks, but skin pain can last 1 - 6 weeks in a primary (the initial) HSV attack.

·         Other Symptoms. Some patients experience other symptoms as well, which may occur before the actual outbreak (called a prodrome ).

·         Fever rising to about 102°F, muscle aches, headache, and flu-like malaise. These general symptoms usually resolve within a week.

·         Lymph glands near the site may be swollen as well.

It may be especially important to identify a primary infection (if possible) and to treat it as soon as possible, since some preliminary research suggests that early treatment may limit the number of viruses that remain latent in the body and reduce the frequency of recurrent outbreaks.

Asymptomatic Stages: Latency and Shedding:

Latency. After an outbreak, the herpes simplex virus goes into a stage known as latency . During that phase, HSV produces no symptoms at all, and the virus is not transmissible.

Asymptomatic Shedding. At certain times, the virus undergoes shedding . During this phase the virus replicates and is capable of being transmitted through fluids and infecting other people. This occurs during an outbreak, but, unfortunately, in a third to half of cases shedding occurs without any symptoms at all. One study reported that about 40% of all HSV-infected people experienced asymptomatic shedding of the virus more than 5% of the time. (Other evidence suggests shedding occurs much more often — between 9 - 28% of the time.) About half of asymptomatic shedding episodes occur within a few days before or after an outbreak and last about 1.5 days. Asymptomatic shedding is much more common with HSV-2 than with HSV-1.

Specific Symptoms of Oral Herpes: Oral herpes (herpes labialis) is most often caused by HSV-1 but can also be caused by HSV-2. It usually affects the lips and, in some primary attacks, the mucous membranes in the mouth. A facial herpes infection on the cheeks or in the nose may occur, but this condition is very uncommon.

Primary Oral Herpes Infection. If the primary (or initial) oral infection causes symptoms, they can be very painful, particularly in small children.

·         Blisters form on the lips but may also erupt on the tongue.

·         The blisters eventually rupture as painful open sores, develop a yellowish membrane before healing, and disappear within 3 - 14 days.

·         Increased salivation and foul breath may be present.

·         Rarely, the infection may be accompanied by difficulty in swallowing, chills, muscle pain, or hearing loss.

In children, the infection usually occurs in the mouth. In adolescents, the primary infection is more apt to occur in the upper part of the throat and cause soreness.

Recurrent Oral Herpes Infection. Most patients experience only a couple of outbreaks a year, although up to 10% of patients experience more frequent recurrences. (HSV-2 oral infections recur less frequently than HSV-1.) Recurrences are usually much milder than primary infections and are known commonly as cold sores or fever blisters (because they may arise during a bout of cold or flu). They usually show up on the outer edge of the lips and rarely affect the gums or throat. (Cold sores are commonly mistaken for the crater-like mouth lesions known as canker sores, which are not associated with HSV.)

Specific Symptoms of Genital Herpes

Genital herpes, which typically affects the penis, vulva, or rectum, is usually caused by HSV-2, although the rate of HSV-1 genital infection is increasing. Studies now report, in fact, that the cases of new symptomatic genital infections are equally split between HSV-1 and HSV-2. Some studies even report a higher incidence of genital HSV-1 cases. (The distinction may not matter, however, since there is no difference in treatments.) Initial genital infections due to HSV-1 may be more severe than those caused by HSV-2. Recurrences tend to be milder and less frequent than with HSV-2, however.

Primary Genital Herpes Infection. The first outbreak usually occurs in or around the genital area between 3 days and 2 weeks after exposure to the virus. If there is a long duration between the initial infection and the first outbreak of symptoms, the episode may be quite mild because the immune system has produced antibodies to the virus by that time. Also, such primary infections are less transmissible, heal faster, and produce fewer symptoms.

In about 80% of initial outbreaks of genital herpes, patients develop diffuse symptoms (flu-like discomfort and fever). The virus sheds for about 3 weeks. Symptoms in men and women are very different from each other.

In women, the pattern of a first infection is often more complicated and severe than in men with some or all of the following events:

·         In addition to general flu-like discomfort, women may experience nerve pain, itching, lower abdominal pain, urinary difficulties, and yeast infections before or during the eruption of the skin blisters.

·         When the outbreak occurs, blisters form raw sores (ulcers) almost immediately. Later they become crusted and fill with a grayish-white fluid. A new crop often occurs during the second week and is accompanied by swollen lymph glands in the groin. The symptoms may last as long as 6 weeks.

·         Lesions commonly appear around the vaginal opening, on the buttocks, in the vagina, or on the cervix. If lesions occur inside the vagina, they are not visible and pain may be minimal. Such women, then, may be unaware that they have genital herpes. In such cases, the blisters produce a discharge that is still highly infectious.

·         Lesions develop in places other than the genital region in 10 - 18% of primary HSV-2 infections. In most of these cases, outbreaks occur in the urethra (the channel that carries urine) where they can cause painful burning during urination. Inflammation of the internal reproductive organs, including the uterus lining (endometrium) and the fallopian tubes, is rare.

In men, about 6 - 10 blisters typically develop on the head or shaft of the penis. They rarely occur at the base. In some cases, they can occur on the buttocks, around the anus, or on the thighs.

Recurrent Genital Herpes Infection. In general, recurrences are much milder than the initial outbreak. The virus sheds for a much shorter period of time (about 3 days) compared to in an initial outbreak of 3 weeks. Women may have only minor itching, and the symptoms may be even milder in men.

On average, individuals experience four recurrences a year, although this varies widely depending on the severity of the initial outbreak. Men, for example, have 20% more recurrences of genital herpes than women even though their symptoms are milder. There are also some differences in frequency of recurrence depending on whether genital herpes is caused by HSV-2 or HSV-1:

·         HSV-2 Genital Herpes Recurrences. HSV-2 genital infections recur more often than HSV-1, and they tend to be more severe. Up to 90% of HSV-2 genital infections recur within the first year after primary infection. Many patients report 5 - 8 recurrences in the first year, but some experience them as often as every 2 weeks. Some, though, have only one initial outbreak without any subsequent recurrences, a rate more typical of those with HSV-1.

·         HSV-1 Genital Herpes Recurrences. In one study, 38% of patients with HSV-1 genital infections had no recurrences in the first year after primary infection, 35% had one recurrence, and 27% had 2 or more recurrences. The average time to recurrence was about 7.5 months. Only 7% of those with genital HSV-1 had two or more recurrences annually for at least 2 years.

According to one study, patients with genital herpes usually notice a significant reduction in recurrence by the seventh year after infection. Some patients, however, particularly those with genital HSV-2, may actually face an increase in recurrence during the first 5 years.

Treatments

Eye ( ocular herpetic infection ). Affects only one eye at a time. Usually caused by HSV-1, but acute cases in the retina are more likely to be due to HSV-2. An estimated 400,000 Americans have recurrent ocular

herpes, with 50,000 new cases occurring each year. The incidence has been highest in children, although it is increasing in older individuals.

Primary: Inflammation of the cornea ( keratitis ), causing sudden and severe pain, blurred vision, or corneal lesions. A cloudy layer can form over the cornea. Swelling may occur around the eyes. Heals within 2 - 3 weeks.

Recurrence: About 40% of people have more than one recurrence, usually keratitis in a single eye, but symptoms may be present in the other eye as well. In the experience of some doctors, short, intense exposure to sunlight may trigger a recurrence, but there is no clear evidence concerning sunlight or any other potential triggers.

Branching, ulcerous lesions of the cornea may occur later in the disease. Stromal keratitis, inflammation of inner layers of the cornea, occurs in about 25% of patients. It is a late immune response to the infection and can, in some cases, be very serious. In the U.S., it is the major cause of blindness in the cornea (which is still very uncommon).

Medications of Ocular HSV. Ocular HSV should be treated carefully since certain treatments may aggravate the condition. Artificial tears may be appropriate for mild cases. Treatments include trifluridine (Viroptic) eye drops or acyclovir or vidarabine (Vira A) ointments. Evidence suggests that all are equally effective. Adding interferon, an immune system booster, to trifluridine may speed healing. Interferon in combination with debridement is also helpful. With treatment, most HSV ocular infections resolve within 5 - 9 days. Taking long-term oral acyclovir after an initial episode of ocular HSV reduces recurrences by about 45%.

Medications for Stromal Keratitis. Oral acyclovir also protects against stromal keratitis in patients with a history of it. Trifluridine or cidofovir may also be protective against it. Neither drug, however, has any effect once stromal keratitis develops. Treatment includes artificial tears for mild cases and topical steroids for moderate to severe inflammation.

Procedures. Patients with ocular HSV may also require debridement, in which the surgeon scrapes away the injured tissue with a cotton swab. A patch or soft contact lens may be worn afterward.

Patients with HSV who show scarring in the cornea may require surgery. In rare cases, a corneal transplant may be necessary.

Brain ( HSV encephalitis ). Usually HSV-1, although HSV-2 is typically the cause in newborns. In about a quarter of HSV-1 encephalitis cases, the infection may be caused by a new strain of the virus. About 2,100 cases occur a year in the U.S. About a third occur in people under 20 years old, half over age 50, and the balance between ages 20 and 50.

Fever, headache, stiff neck, seizures, partial paralysis, stupor, or coma. Other symptoms: smell and taste disturbances, double vision, odd mental states, bizarre or psychotic behavior, loss of the ability to speak or understand, memory loss, confusion, emotional volatility.

Intravenous acyclovir is the treatment of choice for encephalitis and should be started immediately if this complication is suspected. It must be administered for at least 10 days. In rare cases, surgical measures may be needed to relieve the buildup of pressure in the brain.

Finger ( herpetic whitlow ) . One finger, usually thumb or index finger in adults. Any finger in children. HSV-1 the cause in 60% and HSV-2 in 40% of cases. HSV-1 is usually caused by finger-sucking in children or as an occupational condition in adults (usually health care workers not using gloves). HSV-2 is usually acquired by touching infected genital areas.

Primary: Itching or pain, swelling, flushing of the skin, localized tenderness of the infected finger. Clear-yellowish or pus-filled blisters may appear on fingertip lasting 2-3 weeks. Soft tissue around fingernail may become painfully infected. Finger blisters may become secondarily infected with common bacteria, causing fever and swollen glands in the armpit.

Recurrence: Sometimes intense burning, nerve pain, or excessive sensitivity.

Topical acyclovir for acute attack and oral acyclovir for prevention of recurrences.

Herpetic whitlow on the thumb

A herpetic whitlow is an infection of the herpes virus around the fingernail. In children, this is often caused by thumbsucking or finger sucking while they have a cold sore. It is seen in adult health care workers, such as dentists, because of increased exposure to the herpes virus. The use of rubber gloves prevents herpes whitlow in health care workers.

Lower back. Usually caused by HSV-2 and typically occurs in bedridden patients or those with AIDS.

Numbness, tingling of the buttocks or the area around the anus, urinary retention, constipation, and impotence. Weakness or extreme skin sensitivity in the lower extremities, possibly persisting for months. Headaches, stiff neck, and, very rarely, paralysis in lower extremities caused by inflammation of the spinal cord.

Acyclovir or foscarnet in patients resistant to acyclovir.

Peripheral nervous system. Affecting nerves other than in the brain and spine. Usually caused by HSV-1.

Portion of the face temporarily paralyzed (Bell’s palsy). Other areas of the body may exhibit numbness or loss of feeling to the touch.

Acyclovir or similar drugs in combination with oral prednisone.

Other skin areas ( herpetic erythema multiforme ). May follow any form of recurrent HSV. Is relatively rare.

Circular or irregular eruptions on backs of arms and hands. Recurrence of erythema multiforme is common in the same areas. This is actually an allergic reaction that lasts 2 - 3 weeks.

Usually minor and resolves without complications. Acyclovir and symptom relievers (common pain relievers, cold compresses, topical steroids, saline gargles).

Esophagus. Usually caused by HSV-1. Typically occurs in immunocompromised patients or in those taking long-term steroids or other immunosuppressant drugs, but can occur in infected people with normal immune systems.

Difficulty swallowing or burning, squeezing throat pain while swallowing, weight loss, pain in or behind the upper chest while swallowing. Herpes lesions difficult to differentiate from other throat sores.

Intravenous acyclovir may be recommended. Recurrences are rare in patients with healthy immune systems, so preventive therapy is usually unnecessary in these patients.

Cercopithecine Herpesvirus-1, also known as B-Virus, is a member of the herpes group of viruses that occurs naturally in Macaque monkeys and possible in other Old World monkeys. Infection with B-Virus produces very mild disease in the monkey. Most have no obvious evidence of infection. Some monkeys may have vesicles (small blisters) which progress to ulcers in the mouth, on the face, lips, or genitals and/or eye. These lesions spontaneously heal after a few days, but the virus resides permanently in the monkey, and may reactivate and cause ulcerative lesions periodically. These relapses are especially likely to occur when the monkey is "stressed" (like cold sores or fever blisters in humans). During these periods, the virus is shed by the monkey to the environment. However, the virus may also be shed by monkeys without visible lesions or symptoms.

Hepatitis B virus infects the liver of hominoidae, including humans, and causes an inflammation called hepatitis. It is a DNA virus and one of many unrelated viruses that cause viral hepatitis. The disease was originally known as "serum hepatitis"[1] and has caused epidemics in parts of Asia and Africa. Hepatitis B is endemic in China and various other parts of Asia.[2] The proportion of the world’s population currently infected with the virus is estimated at 3 to 6%, but up to a third have been exposed. Symptoms of the acute illness caused by the virus include liver inflammation, vomiting, jaundice, and rarely, death. Chronic hepatitis B may eventually cause liver cirrhosis and liver cancer, a fatal disease with very poor response to current chemotherapy.[3] The infection is preventable by vaccination.

Symptoms and complications: Hepatitis B virus infection may either be acute (self-limiting) or chronic (long-standing). Persons with self-limiting infection clear the infection spontaneously within weeks to months.

Children are less likely than adults to clear the infection. More than 95% of people who become infected as adults or older children will stage a full recovery and develop protective immunity to the virus. However, only 5% of newborns that acquire the infection from their mother at birth will clear the infection. Of those infected between the age of one to six, 70% will clear the infection.

Acute infection with hepatitis B virus is associated with acute viral hepatitis - an illness that begins with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, dark urine, and then progresses to development of jaundice. It has been noted that itchy skin has been an indication as a possible symptom of all hepatitis virus types. The illness lasts for a few weeks and then gradually improves in most affected people. A few patients may have more severe liver disease (fulminant hepatic failure), and may die as a result of it. The infection may be entirely asymptomatic and may go unrecognized.

Chronic infection with Hepatitis B virus may be either asymptomatic or may be associated with a chronic inflammation of the liver (chronic hepatitis), leading to cirrhosis over a period of several years. This type of infection dramatically increases the incidence of hepatocellular carcinoma (liver cancer). Chronic carriers are encouraged to avoid consuming alcohol as it increases their risk for cirrhosis and liver cancer. Hepatitis B virus has been linked to the development of Membranous glomerulonephritis (MGN).

Hepatitis D infection can only occur with a concomitant infection with Hepatitis B virus because the Hepatitis D virus uses the Hepatitis B virus surface antigen to form a capsid.[7] Co-infection with hepatitis D increases the risk of liver cirrhosis and liver cancer.[8] Polyarteritis nodosa is more common in people with hepatitis B infection.

Diagnosis: Hepatitis B viral antigens and antibodies detectable in the blood following acute infection.

Hepatitis B viral antigens and antibodies detectable in the blood following acute infection.

Hepatitis B viral antigens and antibodies detectable in the blood of a chronically infected person

Hepatitis B viral antigens and antibodies detectable in the blood of a chronically infected person

The tests, called assays, for detection of hepatitis B virus infection involve serum or blood tests that detect either viral antigens (proteins produced by the virus) or antibodies produced by the host. Interpretation of these assays is complex.[9]

The hepatitis B surface antigen (HBsAg) is most frequently used to screen for the presence of this infection. It is the first detectable viral antigen to appear during infection. However, early in an infection, this antigen may not be present and it may be undetectable later in the infection as it is being cleared by the host. The infectious virion contains an inner "core particle" enclosing viral genome. The icosahedral core particle is made of 180 or 240 copies of core protein, alternatively known as hepatitis B core antigen, or HBcAg. During this ‘window’ in which the host remains infected but is successfully clearing the virus, IgM antibodies to the hepatitis B core antigen (anti-HBc IgM) may be the only serological evidence of disease.

Shortly after the appearance of the HBsAg, another antigen named as the hepatitis B e antigen (HBeAg) will appear. Traditionally, the presence of HBeAg in a host’s serum is associated with much higher rates of viral replication and enhanced infectivity; however, variants of the hepatitis B virus do not produce the ‘e’ antigen, so this rule does not always hold true. During the natural course of an infection, the HBeAg may be cleared, and antibodies to the ‘e’ antigen (anti-HBe) will arise immediately afterwards. This conversion is usually associated with a dramatic decline in viral replication.

If the host is able to clear the infection, eventually the HBsAg will become undetectable and will be followed by IgG antibodies to the hepatitis B surface antigen and core antigen, (anti-HBs and anti HBc IgG).[10] A person negative for HBsAg but positive for anti-HBs has either cleared an infection or has been vaccinated previously.

Individuals who remain HBsAg positive for at least six months are considered to be hepatitis B carriers. Carriers of the virus may have chronic hepatitis B, which would be reflected by elevated serum alanine aminotransferase levels and inflammation of the liver, as revealed by biopsy. Carriers who have seroconverted to HBeAg negative status, particularly those who acquired the infection as adults, have very little viral multiplication and hence may be at little risk of long-term complications or of transmitting infection to others.

More recently, PCR tests have been developed to detect and measure the amount of viral nucleic acid in clinical specimens. These tests are called viral loads and are used to assess a person’s infection status and to monitor treatment.

Treatment: Acute hepatitis B infection does not usually require treatment because most adults clear the infection spontaneously. Early antiviral treatment may only be required in fewer than 1% of patients, whose infection takes a very aggressive course ("fulminant hepatitis") or who are immunocompromised. On the other hand, treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer. Chronically infected individuals with persistently elevated serum alanine aminotransferase, a marker of liver damage, and HBV DNA levels are candidates for therapy.

Although none of the available drugs can clear the infection, they can stop the virus from replicating, and prevent liver damage such as cirrhosis and liver cancer. Treatments include antiviral drugs such as lamivudine, adefovir and entecavir, and immune system modulators such as interferon alpha. However, some individuals are much more likely to respond than others and this might be because of the genotype of the infecting virus or the patient’s heredity. The treatment works by reducing the viral load, (the amount of virus particles as measured in the blood), which in turn reduces viral replication in the liver.

Infants born to mothers known to carry hepatitis B can be treated with antibodies to the hepatitis B virus (hepatitis B immune globulin or HBIg). When given with the vaccine within twelve hours of birth, the risk of acquiring hepatitis B is reduced 95%. This treatment allows a mother to safely breastfeed her child.

Vaccination:  Several vaccines have been developed for the prevention of hepatitis B virus infection. These rely on the use of one of the viral envelope proteins (hepatitis B surface antigen or HBsAg). The vaccine was originally prepared from plasma obtained from patients who had long-standing hepatitis B virus infection. However, currently, these are more often made using recombinant DNA technology, though plasma-derived vaccines continue to be used; the two types of vaccines are equally effective and safe.

Following vaccination Hepatitis B Surface antigen may be detected in serum for several days; this is known as vaccine antigenaemia.

Microbiology

Structure

A simplified drawing of the HBV particle and surface antigen

A simplified drawing of the HBV particle and surface antigen

Hepatitis B virus (HBV) is a member of the Hepadnavirus family. The virus particle, (virion) consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of protein. The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity.[30] The outer envelope contains embedded proteins which are involved in viral binding of, and entry into, susceptible cells. The virus is one of the smallest enveloped animal viruses with a virion diameter of 42nm, but pleomorphic forms exist, including filamentous and spherical bodies lacking a core. These particles are not infectious and are composed of the lipid and protein that forms part of the surface of the virion, which is called the surface antigen (HBsAg), and is produced in excess during the life cycle of the virus.

Genome

"HBc" redirects here. For other uses, see HBC.

The genome organisation of HBV. The genes overlap

The genome organisation of HBV. The genes overlap

The genome of HBV is made of circular DNA, but it is unusual because the DNA is not fully double-stranded. One end of the full length strand is linked to the viral DNA polymerase. The genome is 3020-3320 nucleotides long (for the full length strand) and 1700-2800 nucleotides long (for the short length strand).[32] The negative-sense, (non-coding), is complementary to the viral mRNA. The viral DNA is found in the nucleus soon after infection of the cell. The partially double-stranded DNA is rendered fully double-stranded by completion of the (+) sense strand and removal of a protein molecule from the (-) sense strand and a short sequence of RNA from the (+) sense strand. Non-coding bases are removed from the ends of the (-)sense strand and the ends are rejoined. There are four known genes encoded by the genome called C, X, P, and S. The core protein is coded for by gene C (HBcAg), and its start codon is preceded by an upstream in-frame AUG start codon from which the pre-core protein is produced. HBeAg is produced by proteolytic processing of the pre-core protein. The DNA polymerase is encoded by gene P. Gene S is the gene that codes for the surface antigen (HBsAg). The HBsAg gene is one long open reading frame but contains three in frame "start" (ATG) codons that divide the gene into three sections, pre-S1, pre-S2, and S. Because of the multiple start codons, polypeptides of three different sizes called large, middle, and small (pre-S1 + pre-S2 + S, pre-S2 + S, or S) are produced.[33] The function of the protein coded for by gene X is not fully understood.[34]

Replication

Hepatitis B virus replication .

Hepatitis B virus replication .

The life cycle of Hepatitis B virus is complex. Hepatitis B is one of a few known non-retroviral viruses which use reverse transcription as a part of its replication process. The virus gains entry into the cell by binding to a receptor on the surface of the cell and enters it by endocytosis. Because the virus multiplies via RNA made by a host enzyme, the viral genomic DNA has to be transferred to the cell nucleus by host proteins called chaperones. The partially double stranded viral DNA is then made fully double stranded and transformed into closed circular supercoiled DNA (cccDNA) that serves as a template for transcription of four viral mRNAs. The largest mRNA, (which is longer than the viral genome), is used to make the new copies of the genome and to make the capsid core protein and the viral DNA polymerase. These four viral transcripts undergo additional processing and go on to form progeny virions which are released from the cell or returned to the nucleus and re-cycled to produce even more copies.[33][35] The long mRNA is then transported back to the cytoplasm where the virion P protein synthesizes DNA via its reverse transcriptase activity.

Serotypes

The virus is divided into four major serotypes (adr, adw, ayr, ayw) based on antigenic epitopes present on its envelope proteins, and into eight genotypes (A-H) according to overall nucleotide sequence variation of the genome. The genotypes have a distinct geographical distribution and are used in tracing the evolution and transmission of the virus. Differences between genotypes affect the disease severity, course and likelihood of complications, and response to treatment and possibly vaccination.

Enterobacter is a genus of common Gram-negative, facultatively-anaerobic, rod-shaped bacteria of the family Enterobacteriaceae. Several strains of the these bacteria are pathogenic and cause opportunistic infections in immunocompromised (usually hospitalized) hosts. The urinary and respiratory tract are the most common sites of infection. Enterobacter can be distinguished from other GNR by virtue of being a ‘fast fermenter’ of lactose (as are Escherichia coli and Klebsiella). Two clinically-important species from this genus are E. aerogenes and E. cloacae.

Enterobacter species, particularly Enterobacter cloacae and Enterobacter aerogenes, are important nosocomial pathogens responsible for various infections, including bacteremia, lower respiratory tract infections, skin and soft tissue infections, urinary tract infections (UTIs), endocarditis, intra-abdominal infections, septic arthritis, osteomyelitis, and ophthalmic infections.

Risk factors for nosocomial Enterobacter species infections include hospitalization of greater than 2 weeks, invasive procedures in the past 72 hours, treatment with antibiotics in the past 30 days, and the presence of a central venous catheter. Specific risk factors for infection with nosocomial multidrug-resistant strains of Enterobacter species include the recent use of broad-spectrum cephalosporins or aminoglycosides and ICU care.

These "ICU bugs" cause significant morbidity and mortality, and infection management is complicated by multiple antibiotic resistance. Enterobacter species possess inducible beta-lactamases, which are undetectable in vitro but are also responsible for resistance during treatment. Physicians treating patients infected with these bacteria are advised to avoid certain antibiotics, particularly third-generation cephalosporins, because resistant mutants can quickly appear. The crucial first step is appropriate identification of the bacteria. Antibiograms must be interpreted with respect to the different resistance mechanisms and their respective frequency, as is reported for bacteria belonging to this genus, even if the resistance mechanisms have not been detected by routine in vitro antibiotic susceptibility testing.

Pathophysiology

Enterobacter species rarely cause disease in a healthy individual. This opportunistic pathogen, similar to other members of the Enterobacteriaceae family, possesses an endotoxin known to play a major role in the pathophysiology of sepsis and its complications.

Although community-acquired infections are occasionally observed, nosocomial infections are, by far, the most frequent. Patients most susceptible to acquiring Enterobacter infections are those who stay in the hospital, especially the ICU, for prolonged periods. Other major risk factors include the prior use of antimicrobial agents, concomitant malignancy (especially hemopoietic and solid organ malignancies) hepatobiliary disease, ulcers of the upper gastrointestinal tract, use of foreign devices such as intravenous catheters, and serious underlying conditions such as burns, mechanical ventilation, and immunosuppression.

The source of infection may be endogenous via colonization of the skin, gastrointestinal tract, or urinary tract or exogenous resulting from the ubiquitous nature of these bacteria. Multiple reports have incriminated the hands of personnel, endoscopes, blood products, devices for monitoring intra-arterial pressure, and stethoscopes as sources of infection. Outbreaks have been traced to various common sources: total parenteral nutrition solutions, isotonic saline solutions, albumin, digital thermometers, and dialysis equipment.

Enterobacter species contain a subpopulation of organisms that produce a beta-lactamase at low-levels. Once exposed to broad-spectrum cephalosporins, the subpopulation of beta-lactamase–producing organisms predominate. Thus, an infection that appears sensitive to cephalosporins at the time of diagnosis may quickly develop into a resistant infection during therapy. Imipenem and cefepime have a more stable beta-lactam ring against the lactamase produced by resistant strains of Enterobacter.

Causes

    * Enterobacter is a gram-negative bacillus belonging to the Enterobacteriaceae family. Other members of this family include Klebsiella, Escherichia, Citrobacter, Serratia, Salmonella, Shigella species, and many others. Enterobacteriaceae are the most frequent bacterial isolates recovered from clinical specimens. These bacteria have an outer membrane that contains, among other things, lipopolysaccharides from which lipid-A plays a major role in sepsis. Lipid-A, also known as endotoxin, is the major stimulus for the release of cytokines, which are the mediators of systemic inflammation and its complications.

    * In the microbiology laboratory, colonies of Enterobacteriaceae appear large, dull-gray, and dry or mucoid on sheep blood agar. All Enterobacteriaceae are glucose fermenters and, consequently, are able to grow in aerobic and anaerobic atmospheres.

    * MacConkey agar is a lactose-containing medium that is selective for nonfastidious gram-negative bacilli such as Enterobacteriaceae. Using the enzymes beta-galactosidase and beta-galactoside permeases, the most frequently encountered species of Enterobacter strains activate the pH indicator (neutral red) included in MacConkey agar, giving a red stain to the growing colonies. Klebsiella and Enterobacter may appear similar as mucoid colonies but can be readily differentiated by a few specific tests. In contrast to Klebsiella, Enterobacter organisms are motile, usually ornithine decarboxylase-positive, and urease-negative.

    * Many different species comprise the genus Enterobacter. For some, no evidence exists to date that proves they can cause human infections. The most frequently isolated species are E cloacae and E aerogenes, followed by E sakazakii, which produces a characteristic yellow pigment. Other species rarely encountered in the clinic include Enterobacter asburiae, Enterobacter gergoviae, Enterobacter taylorae, Enterobacter hormaechei, and Enterobacter cancerogenus. Enterobacter agglomerans has been removed from the genus Enterobacter and renamed Pantoea agglomerans.

Treatment:

Medicine: Antimicrobial therapy is indicated in virtually all infections caused by Enterobacter species.With few exceptions, the major classes of antibiotics used to manage infections with these bacteria are the beta-lactams, the quinolones, the aminoglycosides, and TMP-SMZ.

The choice of appropriate antimicrobial agents is complicated by the fact that the majority of bacteria in this genus are either very resistant to these agents or can develop resistance during antimicrobial therapy. When this occurs, consultation with experts in infectious diseases and microbiology are usually indicated. Newer options include tigecycline. Although it is not indicated specifically for pneumonia or bloodstream infections caused by Enterobacter species, it has excellent in vitro activity against these gram-negative bacilli.

E cloacae, E aerogenes, and most of the others are resistant to the narrow-spectrum penicillins that traditionally have good activity against other Enterobacteriaceae such as E coli (eg, ampicillin, amoxicillin) and to first-generation and second-generation cephalosporins (eg, cefazolin, cefuroxime). They also are usually resistant to cephamycins such as cefoxitin. Resistance to third-generation cephalosporins (eg, ceftriaxone, cefotaxime, ceftazidime) and to extended-spectrum penicillins (eg, ticarcillin, azlocillin, piperacillin) is variable but can develop during treatment. The activity of the fourth-generation cephalosporins (eg, cefepime) is fair, and, for the carbapenems (eg, imipenem, meropenem, ertapenem), activity is excellent. However, resistance has been reported, even to these agents.

·         The bacteria designated by the acronym SERMOR-PROVENF (SER = Serratia, MOR = Morganella, PROV = Providencia, EN = Enterobacter, F = freundii for Citrobacter freundii) have similar, although not identical, chromosomal beta-lactamase genes that are inducible. With Enterobacter, the expression of the gene AmpC, is repressed, but derepression can be induced by beta-lactams. Of these inducible bacteria, mutants with constitutive hyperproduction of beta-lactamases can emerge at a rate between 105 and 108. These mutants are highly resistant to most beta-lactam antibiotics and are considered stably derepressed.

·         These beta-lactamases are from the functional group 1 and molecular class C in the Bush-Jacoby-Medeiros classification of beta-lactamases. They are not inhibited by beta-lactamase inhibitors (eg, clavulanic acid, tazobactam, sulbactam). Ampicillin and amoxicillin, first- and second-generation cephalosporins, and cephamycins are strong AmpC beta-lactamase inducers. They are also rapidly inactivated by these beta-lactamases; thus, resistance is readily documented in vitro.

·         Third-generation cephalosporins and extended-spectrum penicillins, although labile to AmpC beta-lactamases, are weak inducers. Resistance is expressed in vitro only with bacteria that are in a state of stable derepression (mutant hyperproducers of beta-lactamases). However, the physician must understand that organisms considered susceptible by in vitro testing can become resistant during treatment by the following sequence of events: (1) induction of AmpC beta-lactamases, (2) mutation among induced strains, (3) hyperproduction of AmpC beta-lactamases by mutants (stable derepression), and (4) selection of the resistant mutants (the wild type sensitive organisms being killed by the antibiotic).

·         For unknown reasons, extended-spectrum penicillins are less selective than third-generation cephalosporins. The in-therapy resistance phenomenon occurs less frequently with carboxy, ureido, or acylaminopenicillins. This phenomenon has been well documented as a cause of treatment failure with pneumonia and bacteremia; however, the phenomenon is rare with UTIs.

·         Carbapenems are strong AmpC beta-lactamase inducers, but they remain very stable to the action of these beta-lactamases. As a consequence, no resistance to carbapenems, either in vitro or in vivo, can be attributed to AmpC beta-lactamases.

·         The fourth-generation cephalosporins are relatively stable to the action of these beta-lactamases; consequently, they retain moderate activity against the mutant strains of Enterobacter, hyperproducing AmpC beta-lactamases.

·         More recently, the production of extended-spectrum beta-lactamases (ESBLs) has been documented. Usually, these ESBLs are TEM1-derived or SHV1-derived enzymes, and they have been reported since 1983 in K pneumoniae, Klebsiella oxytoca, and E coli. Bush et al classify these ESBLs in group 2be and in molecular class A in their beta-lactamase classification. The location of these enzymes on plasmids favors their transfer between bacteria of the same and of different, genera. Many other gram-negative bacilli may also possess such resistant plasmids.

·         Among Enterobacter, reports indicate that E aerogenes has been the most frequent carrier of ESBL. Unlike the AmpC beta-lactamases, these enzymes are encoded by plasmid DNA and do not possess a molecular mechanism of induction or stable derepression. They are inactivated by the beta-lactamase inhibitors and remain susceptible to cefoxitin (testing cefoxitin is then a useful tool to help differentiate AmpC beta-lactamases from ESBLs).

·         Bacteria-producing ESBLs should be considered resistant to all generations of cephalosporins, all penicillins, and to the monobactams such as aztreonam, even if the in vitro susceptibilities are in the sensitive range according to the CLSI breakpoints. In the past, the CLSI has cautioned physicians regarding the absence of a good correlation with susceptibility when its breakpoints are applied to ESBL-producing bacteria.

·         In 1999, this committee published guidelines for presumptive identification and for confirmation of ESBL production by Klebsiella and E coli guidelines that are often applied to other Enterobacteriaceae. From the above, one can conclude that, when a bacterium of the genus Enterobacter produces ESBL(s) (more than 1 ESBL can be produced by the same bacteria), it does so in addition to the AmpC beta-lactamases that are always present, either in states of inducibility or in states of stable derepression. With stable derepressed mutants, ESBL is almost impossible to detect unless molecular methods such as polymerase chain reaction (PCR) or isoelectric focusing (IEF) electrophoresis are used. For inducible strains, no recommendations have been issued by the CLSI for the detection of ESBL (ie, if PCR and IEF electrophoresis are not readily available).

·         Carbapenems are the only reliable beta-lactam drugs for the treatment of severe Enterobacter infections, and fourth-generation cephalosporins are a distant second choice. The association of an extended-spectrum penicillin with a beta-lactamase inhibitor remains a controversial issue for therapy of ESBL-producing organisms.

·         Resistance to carbapenems is rare but has been reported for imipenem in strains of E cloacae with a high MIC. The beta-lactamases implicated were NMC-A and IMI-1, both molecular class A and functional group 2f carbapenemases, which are inhibited by clavulanic acid and then able to hydrolyze all the beta-lactams not associated with a beta-lactamase inhibitor.

·         Hyperproduction (stable derepression) of AmpC beta-lactamases associated with some decrease in permeability to the carbapenems may also cause resistance to these agents.

    * Aminoglycosides

    *

          o Aminoglycoside resistance is relatively frequent and varies widely among centers.

          o As with other members of Enterobacteriaceae, this resistance results from the production of different aminoglycoside-inactivating enzymes.

    * Quinolones and TMP-SMZ

    *

          o Resistance to fluoroquinolones is relatively rare.

          o Resistance to TMP-SMZ is more frequent.

Surgical Care

Surgical care is indicated as for other sources of infection: drainage or debridement of abscesses, infected collections, or osteomyelitic foci.

In some instances, the clinician must consider this option instead of percutaneous drainage with CT-scan guidance. The severity of the infection and the size of the collection to be drained are among the parameters to consider when choosing the best option for the patient.

For endocarditis, valvular replacement is also indicated, particularly when emboli or intractable heart failure is present.

Consultations

This opportunistic pathogen causes severe and frequently life-threatening infections that can originate in virtually any body compartment. Infection warrants consultation with many different subspecialists.

    * Consultation with an infectious diseases specialist helps in the selection of antimicrobial agents, taking into account the multiple mechanisms of resistance to different classes of antimicrobial agents and the lack of correlation between crude in vitro susceptibility results and true clinical efficacy for most of the beta-lactams.

    * Intensive care specialists, when appropriate, can help in the management of severe sepsis or septic shock.

    * General internal medicine and/or medical subspecialists (eg, cardiologists, gastroenterologists, nephrologists, rheumatologists, pulmonologists) may be helpful.

    * Surgeons may help with the drainage of infected collections, if indicated.

    * Consult neonatologists for neonatal sepsis and, possibly, general pediatricians or pediatric subspecialists (including pediatric surgeons).

    * Radiologists and nuclear medicine physicians may help select the best imaging study according to patient’s specific problems and (radiologists) may be needed to perform percutaneous drainage of infected collections.

When your kidneys fail, you need treatment to replace the work your kidneys normally perform.

You may choose to forgo treatment. If you choose to receive treatment, your choices include hemodialysis, peritoneal dialysis, and kidney transplantation. Each treatment has advantages and disadvantages

When Your Kidneys Fail

Healthy kidneys clean your blood by removing excess fluid, minerals, and wastes. They also make hormones that keep your bones strong and your blood healthy. When your kidneys fail, harmful wastes build up in your body, your blood pressure may rise, and your body may retain excess fluid and not make enough red blood cells. When this happens, you need treatment to replace the work of your failed kidneys.

Hemodialysis: Hemodialysis cleans and filters your blood using a machine to temporarily rid your body of harmful wastes, extra salt, and extra water. Hemodialysis helps control blood pressure and helps your body keep the proper balance of important chemicals such as potassium, sodium, calcium, and bicarbonate.

Dialysis can replace part of the function of your kidneys. Diet, medications, and fluid limits are often needed as well. Your diet, fluids, and the number of medications you need will depend on which treatment you choose.

Hemodialysis uses a special filter called a dialyzer that functions as an artificial kidney to clean your blood. The dialyzer is a canister connected to the hemodialysis machine
Hemodialysis.

Arteriovenous fistula.Several months before your first hemodialysis treatment, an access to your bloodstream will need to be created. You may need to stay overnight in the hospital, but many patients have their access created on an outpatient basis. This access provides an efficient way for blood to be carried from your body to the dialyzer and back without causing discomfort. The two main types of access are a fistula and a graft.

• A surgeon makes a fistula by using your own blood vessels; an artery is connected directly to a vein, usually in your forearm. The increased blood flow makes the vein grow larger and stronger so it can be used for repeated needle insertions. This kind of access is the preferred type. It may take several weeks to be ready for use.
• A graft connects an artery to a vein by using a synthetic tube. It doesn’t need to develop as a fistula does, so it can be used sooner after placement. But a graft is more likely to have problems with infection and clotting.

Possible Complications: Vascular access problems are the most common reason for hospitalization among people on hemodialysis. Common problems include infection, blockage from clotting, and poor blood flow. These problems can keep your treatments from working. You may need to undergo repeated surgeries in order to get a properly functioning access.

Other problems can be caused by rapid changes in your body’s water and chemical balance during treatment. Muscle cramps and hypotension—a sudden drop in blood pressure—are two common side effects. Hypotension can make you feel weak, dizzy, or sick to your stomach.

You’ll probably need a few months to adjust to hemodialysis. Side effects can often be treated quickly and easily, so you should always report them to your doctor and dialysis staff. You can avoid many side effects if you follow a proper diet, limit your liquid intake, and take your medicines as directed.

Diet for Hemodialysis: Hemodialysis and a proper diet help reduce the wastes that build up in your blood. A dietitian is available at all dialysis centers to help you plan meals according to your doctor’s orders. When choosing foods, remember to

• eat balanced amounts of high-protein foods such as meat, chicken, and fish.
• control the amount of potassium you eat. Potassium is a mineral found in salt substitutes; some fruits, such as bananas and oranges; vegetables; chocolate; and nuts. Too much potassium can be dangerous to your heart.
• limit how much you drink. When your kidneys aren’t working, water builds up quickly in your body. Too much liquid makes your tissues swell and can lead to high blood pressure, heart trouble, and cramps and low blood pressure during dialysis.
• avoid salt. Salty foods make you thirsty and make your body hold water.
• limit foods such as milk, cheese, nuts, dried beans, and dark colas. These foods contain large amounts of the mineral phosphorus. Too much phosphorus in your blood causes calcium to be pulled from your bones, which makes them weak and brittle and can cause arthritis. To prevent bone problems, your doctor may give you special medicines, which you must take with meals every day as directed.

• + You don’t have to have a partner or keep equipment in your home.

Cons

• - Treatments are scheduled by the center and are relatively fixed.
• - You must travel to the center for treatment.
• - This treatment has the strictest diet and fluid limits of all.
• - You will need to take—and pay for—more medications.
• - You may have more frequent ups and downs in how you feel from day to day.
• - It may take a few hours to feel better after a treatment.

Peritoneal Dialysis

Peritoneal dialysis is another procedure that removes wastes, chemicals, and extra water from your body. This type of dialysis uses the lining of your abdomen, or belly, to filter your blood. This lining is called the peritoneal membrane and acts as the artificial kidney.

How Peritoneal Dialysis Works

A mixture of minerals and sugar dissolved in water, called dialysis solution, travels through a catheter into your belly. The sugar—called dextrose—draws wastes, chemicals, and extra water from the tiny blood vessels in your peritoneal membrane into the dialysis solution. After several hours, the used solution is drained from your abdomen through the tube, taking the wastes from your blood with it. Then your abdomen is refilled with fresh dialysis solution, and the cycle is repeated. The process of draining and refilling is called an exchange.

Types of Peritoneal Dialysis

Three types of peritoneal dialysis are available.

1. Continuous Ambulatory Peritoneal Dialysis (CAPD)
   CAPD requires no machine and can be done in any clean, well-lit place. With CAPD, your blood is always being cleaned. The dialysis solution passes from a plastic bag through the catheter and into your abdomen, where it stays for several hours with the catheter sealed. The time period that dialysis solution is in your abdomen is called the dwell time. Next, you drain the dialysis solution into an empty bag for disposal. You then refill your abdomen with fresh dialysis solution so the cleaning process can begin again. With CAPD, the dialysis solution stays in your abdomen for a dwell time of 4 to 6 hours, or more. The process of draining the used dialysis solution and replacing it with fresh solution takes about 30 to 40 minutes. Most people change the dialysis solution at least four times a day and sleep with solution in their abdomens at night. With CAPD, it’s not necessary to wake up and perform dialysis tasks during the night.
2. Continuous Cycler-assisted Peritoneal Dialysis (CCPD)
   CCPD uses a machine called a cycler to fill and empty your abdomen three to five times during the night while you sleep. In the morning, you begin one exchange with a dwell time that lasts the entire day. You may do an additional exchange in the middle of the afternoon without the cycler to increase the amount of waste removed and to reduce the amount of fluid left behind in your body.
3. Combination of CAPD and CCPD
   If you weigh more than 175 pounds or if your peritoneum filters wastes slowly, you may need a combination of CAPD and CCPD to get the right dialysis dose. For example, some people use a cycler at night but also perform one exchange during the day. Others do four exchanges during the day and use a minicycler to perform one or more exchanges during the night. You’ll work with your health care team to determine the best schedule for you.

Possible Complications: The most common problem with peritoneal dialysis is peritonitis, a serious abdominal infection. This infection can occur if the opening where the catheter enters your body becomes infected or if contamination occurs as the catheter is connected or disconnected from the bags. Infection is less common in presternal catheters, which are placed in the chest. Peritonitis requires antibiotic treatment by your doctor.

To avoid peritonitis, you must be careful to follow procedures exactly and learn to recognize the early signs of peritonitis, which include fever, unusual color or cloudiness of the used fluid, and redness or pain around the catheter. Report these signs to your doctor or nurse immediately so that peritonitis can be treated quickly to avoid additional problems.

Diet for Peritoneal Dialysis: A peritoneal dialysis diet is slightly different from an in-center hemodialysis diet.

• You’ll still need to limit salt and liquids, but you may be able to have more of each, compared with in-center hemodialysis.
• You must eat more protein.
• You may have different restrictions on potassium. You may even need to eat high-potassium foods.
• You may need to cut back on the number of calories you eat because there are calories in the dialysis fluid that may cause you to gain weight.

Your doctor and a dietitian who specializes in helping people with kidney failure will be able to help you plan your meals.

Dialysis Is Not a Cure

Hemodialysis and peritoneal dialysis are treatments that help replace the work your kidneys did. These treatments help you feel better and live longer, but they don’t cure kidney failure. Although patients with kidney failure are now living longer than ever, over the years kidney disease can cause problems such as heart disease, bone disease, arthritis, nerve damage, infertility, and malnutrition. These problems won’t go away with dialysis, but doctors now have new and better ways to prevent or treat them. You should discuss these complications and their treatments with your doctor.

Kidney Transplantation: Kidney transplantation surgically places a healthy kidney from another person into your body. The donated kidney does enough of the work that your two failed kidneys used to do to keep you healthy and symptom free.

Complications: Transplantation is the closest thing to a cure. But no matter how good the match, your body may reject your new kidney. A common cause of rejection is not taking medication as prescribed.

Your doctor will give you medicines called immunosuppressants to help prevent your body’s immune system from attacking the kidney, a process called rejection. You’ll need to take immunosuppressants every day for as long as the transplanted kidney is functioning. Sometimes, however, even these medicines can’t stop your body from rejecting the new kidney. If this happens, you’ll go back to some form of dialysis and possibly wait for another transplant.

Immunosuppressants weaken your immune system, which can lead to infections. Some medicines may also change your appearance. Your face may get fuller; you may gain weight or develop acne or facial hair. Not all patients have these problems, though, and diet and makeup can help.

Immunosuppressants work by diminishing the ability of immune cells to function. In some patients, over long periods of time, this diminished immunity can increase the risk of developing cancer. Some immunosuppressants can cause cataracts, diabetes, extra stomach acid, high blood pressure, and bone disease. When used over time, these drugs may also cause liver or kidney damage in a few patients.

Withdrawing from Treatment: For many people, dialysis and transplantation not only extend life but also improve quality of life. For others who have serious ailments in addition to kidney failure, dialysis may seem a burden that only prolongs suffering. You have the right to refuse or withdraw from dialysis. You may want to speak with your spouse, family, religious counselor, or social worker as you make this decision.

If you withdraw from dialysis treatments or refuse to begin them, you may live for a few days or for several weeks, depending on your health and your remaining kidney function. Your doctor can give you medicines to make you more comfortable during this time. You may start or resume your treatments if you change your mind about refusing dialysis.

Even if you’re satisfied with your quality of life on dialysis, you should think about circumstances that might make you want to stop dialysis treatments. At some point in a medical crisis, you might lose the ability to express your wishes to your doctor. An advance directive is a statement or document in which you give instructions either to withhold treatment or to provide it, depending on your wishes and the specific circumstances.

An advance directive may be a living will, a document that details the conditions under which you would want to refuse treatment. You may state that you want your health care team to use all available means to sustain your life. Or you may direct that you be withdrawn from dialysis if you become permanently unresponsive or fall into a coma from which you won’t awake. In addition to dialysis, other life-sustaining treatments you may choose or refuse include

• cardiopulmonary resuscitation (CPR)
• tube feedings
• mechanical or artificial respiration
• antibiotics
• surgery
• blood transfusions

Another form of advance directive is called a durable power of attorney for health care decisions or a health care proxy. In this type of advance directive, you assign a person to make health care decisions for you if you become unable to make them for yourself. Make sure the person you name understands your values and is willing to follow through on your instructions.

Chronic Kidney Disease (CKD): Chronic kidney disease includes conditions that damage your kidneys and decrease their ability to keep you healthy by doing the jobs listed. If kidney disease gets worse, wastes can build to high levels in your blood and make you feel sick. You may develop complications like high blood pressure, anemia (low blood count), weak bones, poor nutritional health and nerve damage. Also, kidney disease increases your risk of having heart and blood vessel disease. These problems may happen slowly over a long period of time. Chronic kidney disease may be caused by diabetes, high blood pressure and other disorders. Early detection and treatment can often keep chronic kidney disease from getting worse. When kidney disease progresses, it may eventually lead to kidney failure, which requires dialysis or a kidney transplant to maintain life.

• 26 million Americans have CKD and another 20 million more are at increased risk.
• Early detection can help prevent the progression of kidney disease to kidney failure.
• Heart disease is the major cause of death for all people with CKD.
• Glomerular filtration rate (GFR) is the best estimate of kidney function.
• Hypertension causes CKD and CKD causes hypertension.
• Persistent proteinuria means CKD.
• High risk groups include those with diabetes, hypertension and family history of kidney disease.
• African Americans, Hispanics, Pacific Islanders, Native Americans and Seniors are at increased risk.
• Three simple tests can detect CKD: blood pressure, urine albumin and serum creatinine.

Tests

Chronic kidney disease usually causes no symptoms in its early stages. Only lab tests can detect any developing problems. Anyone at increased risk for chronic kidney disease should be routinely tested for development of this disease.

• Urine, blood, and imaging tests are used to detect kidney disease, as well as to follow its progress.
• All of these tests have limitations. They are often used together to develop a picture of the nature and extent of the kidney disease.

Urine tests

urinalysis: Analysis of the urine affords enormous insight into the function of the kidneys. The first step in urinalysis is doing a dipstick test. The dipstick has reagents that check the urine for the presence of various normal and abnormal constituents including protein. Then, the urine is examined under a microscope to look for red and white blood cells, and the presence of casts and crystals (solids).

Only minimal quantities of protein are present in urine normally. A positive result on a dipstick test for protein is abnormal. More sensitive than a dipstick test for protein is a laboratory estimation of the urine albumin (protein) and creatinine in the urine. The ratio of albumin (protein) and creatinine in the urine provides a good estimate of albumin (protein) excretion per day.

Twenty-four–hour urine tests: This test requires you to collect all of your urine for 24 consecutive hours. The urine may be analyzed for protein and waste products. The presence of protein in the urine indicates kidney damage. The amount of creatinine and urea excreted in the urine can be used to calculate the level of kidney function and the glomerular filtration rate (GFR).

Glomerular filtration rate (GFR): The GFR is a standard means of expressing overall kidney function. As kidney disease progresses, GFR falls. The normal GFR is about 100-140 mL/min in men and 85-115 mL/min in women. It decreases in most people with age. The GFR may be calculated from the amount of waste products in the 24-hour urine or by using special markers administered intravenously. Patients are divided into five stages of chronic kidney disease based on their GFR (see Table 1 above).

Blood tests

Creatinine and urea (BUN) in the blood: Are the most commonly used blood tests to screen for, and monitor renal disease. Creatinine is a breakdown product of normal muscle breakdown. Urea is the waste product of breakdown of protein. The level of these substances rises in the blood as kidney function worsens.

Estimated GFR: The laboratory or your physician may calculate an estimated GFR using the information from your blood work. It is important to be aware of your estimated GFR and stage of chronic kidney disease. Your physician uses your stage of kidney disease to recommend additional testing and suggestions on management.

Electrolyte levels and acid-base balance: Kidney dysfunction causes imbalances in electrolytes,especially potassium, phosphorus, and calcium. High potassium is a particular concern. The acid-base balance of the blood is usually disrupted as well.

Decreased production of the active form of vitamin D can cause low levels of calcium in the blood. Inability to excrete phosphorus by failing kidneys causes its levels in the blood to rise. Testicular or ovarian hormone levels may also be abnormal.

Blood cell counts: Because kidney disease disrupts blood cell production and shortens the survival of red cell, the red blood cell count and hemoglobin may be low (anemia). Some patients may also have iron deficiency due to blood loss in their gastrointestinal system. Other nutritional deficiencies may also impair the production of red cells.

Other tests

Ultrsound:Ultrasound is often used in the diagnosis of kidney disease. An ultrasound is a noninvasive type of test. In general, kidneys are shrunken in size in chronic kidney disease, although they may be normal or even large in size in cases caused by adult polycystic kidney disease, diabetic nephropathy, and amyloidosis. Ultrasound may also be used to diagnose the presence of urinary obstruction, kidney stone and also to assess the blood flow into the kidneys.

Biopsy: A sample of the kidney tissue (biopsy) is sometimes required in cases in which the cause of the kidney disease is unclear. Usually, a biopsy can be collected with local anesthesia only by introducing a needle through the skin into the kidney. This is usually done as an outpatient procedure, though some institutions may require an overnight hospital stay

Treatment: Chronic kidney disease is a disease that must be managed in close consultation with your healthcare provider. Self-treatment is not appropriate.

• There are, however, several important dietary rules you can follow to help slow the progression of your kidney disease and decrease the likelihood of complications.
• This is a complex process and must be individualized, generally with the help of your healthcare provider and a registered dietitian.

The following are general dietary guidelines:

• Protein restriction: Decreasing protein intake may slow the progression of chronic kidney disease. A dietitian can help you determine the appropriate amount of protein for you.
• Salt restriction: Limit to 4-6 grams a day to avoid fluid retention and help control high blood pressure.
• Fluid intake: Excessive water intake does not help prevent kidney disease. In fact, your doctor may recommend restriction of water intake.
• Potassium restriction: This is necessary in advanced kidney disease because the kidneys are unable to remove potassium. High levels of potassium can cause abnormal heart rhythms. Examples of foods high in potassium include bananas, oranges, nuts, and potatoes.
• Phosphorus restriction: Decreasing phosphorus intake is recommended to protect bones. Eggs, beans, cola drinks, and dairy products are examples of foods high in phosphorus.

If you have a condition such as diabetes, high blood pressure, or high cholesterol underlying your chronic kidney disease, take all medications as directed and see your healthcare provider as recommended for follow-up and monitoring.

A variety of species of clostridium are associated with invasive infection in humans i.e. C. perfringens, novyi, septicum, histolyticum, tertium, bifermentans, sporogenes. They are not highly pathogenic when introduced into healthy tissues; but in the presence of tissue injury, in particular damaged muscle, they can cause a rapidly progressive devastating infection characterised by the accumulation of gas and the extensive destruction of muscle and connective tissue. Pathogenesis is due to the production of various toxins with necrotising, haemolytic or other destructive properties.

 There are three types of clostridial wound infection: wound contamination, anaerobic cellulitis, and true myonecrosis (gas gangrene). 80 to 90% of isolations of C. perfringens from hospital represent wound contamination which does not herald invasive infection. Anaerobic cellutitis is a clostridial infection that does not involve the muscle and is much less aggressive than gas gangrene. Germination occurs in damaged tissue where damage to the blood supply has reduced the supply of oxygen. The vegetative bacilli multiply and anaerobic cellulitis develops after several days. The marked gas formation is detectable by the resulting crepitus. Gas gangrene is an intensively aggressive highly lethal infection, primary of muscle. After the germination of clostridial spores in the injured muscle, bacterial multiplication and toxin production occur. A self-perpetuating cycle of progressive tissue injury ensue. The onset of the disease is sudden, usually following an onset of 6 to 72 hours after injury or abdominal surgery. Of the six clostridial species capable of producing gas gangrene, C. perfringens account for the majority of cases.

Symptoms: Gas gangrene produces severe pain in the infected area. Initially, the area is swollen and pale, but eventually turns red, then bronze, and finally blackish green. Large blisters often form. Gas bubbles may be visible in the blister fluid or may be felt under the skin. The odor of any wound drainage is described as sweet or mousy, unlike the putrid odor typical of other anaerobic infections.

As the infection progresses, the person becomes sweaty and very anxious; vomiting may also occur. Rapid heart rate and rapid breathing are common. These effects are caused by toxins produced by the bacteria. Typically, the person remains very alert until late in the illness, when very low blood pressure (shock) and coma develop, followed rapidly by death.

Diagnosis: The initial diagnosis of gas gangrene is based on the person’s symptoms and a physical examination. Finding gas bubbles in the muscle tissue on x-ray increases a doctor’s suspicion of a clostridial infection, but gas bubbles may also occur with non-clostridial anaerobic infections. Examination of secretions from the wound under a microscope may reveal the clostridia, and cultures can confirm their presence—but because gas gangrene is so rapidly fatal, treatment is always begun before the culture results are available.

Treatment: Without treatment, gas gangrene is fatal within 48 hours. Even with treatment, death occurs in about one of eight people with infection of a limb and in about two of three people with infection on the trunk.

If gas gangrene is suspected, treatment must begin immediately. High doses of antibiotics, typically penicillin and clindamycinSome Trade Names
CLEOCIN
, are given, and all dead and infected material is removed surgically. About one of five people with gas gangrene in a limb requires amputation of the infected limb. Treatment in a high-pressure oxygen (hyperbaric oxygen) chamber is of uncertain value; moreover, such chambers are not readily available.

corynebacterium infections are gram-positive, catalase-positive, aerobic or facultatively anaerobic, generally nonmotile rods. The genus is composed of the species Corynebacterium diphtheriae and the nondiphtherial corynebacteria, collectively referred to as diphtheroids. Nondiphtherial corynebacteria, originally thought to be mainly contaminants, recently have been recognized as pathogenic, especially in immunocompromised hosts.

Approximately 20 years ago, taxonomic changes were made to diverse genera previously included within the coryneform groups. The reclassification is based on the degree of homology of RNA oligonucleotides between groups. Based on this reclassification, for example, Corynebacterium haemolyticum became Arcanobacterium haemolyticum and JK group became Corynebacterium jeikeium (Coyle, 1990).

Prior to the 1990s, the incidence of diphtheria had been declining. However, cases of epidemic diphtheria in the former Soviet Union have been recently reported. The more common scenario today is bacteremia with nondiphtherial corynebacteria associated with device infections (venous access catheters, heart valves, neurosurgical shunts, peritoneal catheters), as well as meningitis, septic arthritis, and urinary tract infections.

Types:

C diphtheriae

C diphtheriae infection is classically characterized by a local inflammation, usually in the upper respiratory tract, associated with toxin-mediated cardiac and neural disease. Three strains of C diphtheriae are recognized, in decreasing order of virulence: gravis, intermedius, and mitis. These strains all produce an identical toxin, but the gravis strain is potentially more virulent because it grows faster and depletes the local iron supply, allowing for earlier and greater toxin production. Toxin production is encoded on the tox gene, which, in turn, is carried on a lysogenic beta phage. When DNA of the phage integrates into the host bacteria’s genetic material, the bacteria develop the capacity to produce this polypeptide toxin.

The toxin is a single polypeptide with an active (A) domain, a binding (B) domain, and a hydrophobic segment known as the T domain, which helps release the active part of the polypeptide into the cytoplasm. In the cytosol, the A domain catalyzes the transfer of an adenosine diphosphate-ribose molecule to one of the elongation factors (eg elongation factor 2 [EF2]) responsible for protein synthesis. This transfer inactivates the factor, thereby inhibiting cellular protein synthesis. Inhibiting all the protein synthesis in the cell causes the cell death.

In this manner, the toxin is responsible for many of the clinical manifestations of the disease. As little as 0.1 µg can cause death in guinea pigs. In 1890, von Behring and Kitasato demonstrated that sublethal doses of the toxin induced neutralizing antibodies against the toxin in horses. In turn, this antiserum passively protected the animals against death following challenge infection

corynebacteria ( diphtheroids)

Nondiphtherial corynebacteria are ubiquitous in nature and commonly colonize human skin and mucous membranes. Only recently has the role of these organisms in human infections been appreciated. In fact, many of these organisms cannot be speciated or typed easily, even in research laboratories, although recent advances in polymerase chain reaction (PCR) technology are improving our ability to identify these bacteria. Seven or 8 major species or groups are labeled. The review by Coyle and Lipsky is an in-depth evaluation of the role of coryneform bacteria in causing infections.

Specific pathogenic groups or species include the following:

• Corynebacterium ulcerans
• Corynebacterium pseudotuberculosis (also known as Corynebacterium ovis)
• Corynebacterium pyogenes
• A haemolyticum
• Corynebacterium aquaticum
• Corynebacterium pseudodiphtheriticum (also known as Corynebacterium hofmannii)
• Group D2 (also known as Corynebacterium urealyticum)
• Group E
• Corynebacterium jeikeium (ie, group JK)

Some of these species also are pathogenic in animals, especially in livestock; others appear specific to humans. Depending on the species, both skin and internal organ systems can be affected, particularly in patients who are elderly, are immunosuppressed, or have multiorgan dysfunction. While most species (eg, C ulcerans) are sensitive to many antibiotics, some (eg, group D2) can be highly resistant and require susceptibility testing for optimal treatment

Treatment:

Antitoxins: Administered to neutralize toxin responsible for diphtheria

Antibiotics: Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Erythromycin: Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. In children, age, weight, and severity of infection determine proper dosage. When bid dosing desired, half of total daily dose may be taken q12h. For more severe infections, double dose. Parenteral erythromycin is available as gluceptate or lactobionate. All PO dosage forms produce relatively similar effective base serum concentrations. Equivalent dosage of various formulations may be used for base.

May increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; lovastatin and simvastatin increase risk of rhabdomyolysis.

Caution in liver disease; estolate formulation may cause cholestatic jaundice; adverse GI effects common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

Vancomycin (Vancocin): Antibiotic useful against gram-positive organisms, particularly C jeikeium. Useful to treat septicemia, skin structure infections, and IV line infections/bacteremias.

Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; if taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants.

Caution in renal failure; neutropenia; red man syndrome caused by IV infusion that is too rapid (dose given over few min) but rarely happens when dose given over 2 h or by PO route; red man syndrome not allergic reaction.

Rifampin (Rifadin): Nondiphtherial  corynebacteria often are susceptible.

Obtain CBC and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; high-dose intermittent therapy and interruption of therapy associated with thrombocytopenia, which is reversible with discontinuation of therapy as soon as purpura occurs; if treatment continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur; can cause reddish discoloration of urine, sweat, sputum, and tears; soft contact lenses may be permanently stained.

Induces microsomal enzymes, which may decrease effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur)

Cholera is an acute, diarrheal illness caused by infection of the intestine with the bacterium Vibrio cholerae. The infection is often mild or without symptoms, but sometimes can be severe.

A person may get cholera by drinking water or eating food contaminated with the cholera bacterium. In an epidemic, the source of the contamination is usually the feces (stool) of an infected person. The disease can spread rapidly in areas with inadequate treatment of sewage and drinking water.

The cholera bacterium may also live in the environment in brackish rivers and coastal waters. Shellfish eaten raw have been a source of cholera. The disease is not likely to spread directly from one person to another; therefore, casual contact with an infected person is not a risk for becoming ill.

All travelers to areas where cholera has occurred should observe the following recommendations:

• Drink only water that you have boiled or treated with chlorine or iodine. Other safe beverages include tea and coffee made with boiled water and carbonated, bottled beverages with no ice.
• Eat only foods that have been thoroughly cooked and are still hot, or fruit that you have peeled yourself.
• Avoid undercooked or raw fish or shellfish, including ceviche.
• Make sure all vegetables are cooked, avoid salads.
• Avoid foods and beverages from street vendors.
• Do not bring perishable seafood back to the United States.

A simple rule of thumb is "Boil it, cook it, peel it, or forget it."

Symptoms: Approximately 1 in 20 infected persons has severe disease characterized by:

• profuse watery diarrhea
• vomiting, and
• leg cramps.

Cholera can be simply and successfully treated by immediate replacement of the fluid and salts lost through diarrhea. Patients can be treated with oral rehydration solution, a prepackaged mixture of sugar and salts to be mixed with water and drunk in large amounts. This solution is used throughout the world to treat diarrhea. Severe cases also require intravenous fluid replacement. With prompt rehydration, fewer than 1% of cholera patients die.

Antibiotics shorten the course and diminish the severity of the illness, but they are not as important as rehydration. Persons who develop severe diarrhea and vomiting in countries where cholera occurs should seek medical attention promptly.

Cellulitis is a spreading bacterial infection of the skin and tissues beneath the skin. Cellulitis usually begins as a small area of tenderness, swelling, and redness. As this red area begins to enlarge, the person may develop a fever—sometimes with chills and sweats—and swollen lymph nodes ("swollen glands") near the area of infected skin.

Cellulitis refers to an infection also involving the skin’s deeper layers: the dermis and subcutaneous tissue. cellulitis is caused by Staphylococcus, the same bacteria that cause many cases of impetigo. Occasionally, other bacteria may cause cellulitis as well.

Cellulitis may occur anywhere on the body, but the leg is the most common site of the infection (particularly in the area of the tibia or shin bone and in the foot), followed by the arm, and then the head and neck areas. In special circumstances, such as following surgery or trauma wounds, cellulitis can develop in the abdomen or chest areas.

Symptoms: The signs of cellulitis include redness, warmth, swelling, and pain in the involved tissues. Any skin wound or ulcer that exhibits these signs may be developing cellulitis.

Other forms of noninfected inflammation may mimic cellulitis. People with poor leg circulation, for instance, often develop scaly redness on the shins and ankles; this is often mistaken for the bacterial infection of cellulitis.

Treatment: First, it is crucial for the doctor to distinguish whether or not the inflammation is due to an infection. The history and physical exam can provide clues in this regard, as can sometimes an elevated white blood cell count. A culture for bacteria may also be of value, but in many cases of cellulitis, the concentration of bacteria may be low and cultures fail to demonstrate the causative organism.

When it is difficult or impossible to distinguish whether or not the inflammation is due to an infection, doctors sometimes treat with antibiotics just to be sure. If the condition does not respond, it may need to be addressed by different methods dealing with types of inflammation that are not infected. For example, if the inflammation is thought to be due to an autoimmune disorder, treatment may be with a corticosteroids.

Antibiotics, such as derivatives of penicillin or other types of antibiotics that are effective against the responsible bacteria, are used to treat cellulitis. If the bacteria turn out to be resistant to the chosen antibiotics or in patients who are allergic to penicillin, other appropriate antibiotics can be substituted. In many cases, treatment requires the administration of intravenous antibiotics in a hospital setting, since oral antibiotics may not always provide sufficient penetration of the injury to be effective. In certain cases, intravenous antibiotics can be administered at home.

In all cases, physicians choose a treatment based upon many factors, including the location and extent of the infection, the type of bacteria causing the infection, and the overall health status of the patient