Articles on Medical Diseases and Conditions

Tag: Clostridium difficile

  • Infectious Diarrhea due to Bacterial Agents

    Diarrhea caused by Clostridium difficile related to antibiotic therapy was discussed previously. Many cases of diarrhea produced by bacterial infection are also part of the spectrum of “food poisoning.” Clostridium botulinum generates a preformed neurotoxin and in adults is associated with improperly canned food. Usually there is no diarrhea. The organism was discussed earlier with the clostridia. Staphylococcus aureus also generates a preformed toxin after it is allowed to grow in certain foods (typically custards, creams, potato salad, and ham, usually when allowed to remain warm). Symptoms most often occur less than 7 hours after ingestion of the food (average, 3 hours) and consist of nausea, vomiting, abdominal cramps, and diarrhea.

    Clostridium perfringens occasionally may contaminate food, typically meat or gravy, that has been cooked and then allowed to cool slowly. Symptoms are due to exotoxin formed within the intestine, occur about 12 hours after eating, and consist of simultaneous abdominal cramps and diarrhea without fever or vomiting. Bacillus cereus uncommonly causes food poisoning, usually in fried rice that is kept warm. Bacillus cereus forms an endotoxin that can either be preformed (such as C. botulinum or S. aureus) or produced as the bacteria multiply after being ingested by the patient (such as C. perfringens). Diarrhea without vomiting is the major symptom. Vibrio parahaemolyticus is ingested with raw or poorly cooked fish or shellfish. The organism may invade tissue or may produce an exotoxin. Average onset of symptoms is 12-24 hours after ingestion. Symptoms are vomiting, nausea, cramps, diarrhea, chill, and fever.

    Other bacteria associated with diarrhea. Several bacterial species cause infectious diarrhea but are not ordinarily considered to be agents of food poisoning because of their relatively long incubation periods. These include Salmonella, Shigella, Yersinia enterocolitica, Campylobacter fetus ssp. jejuni, E. coli, Vibrio cholerae, and possibly V. parahaemolyticus. Other bacteria less often involved that should be mentioned are Aeromonas hydrophila and Plesiomonas shigelloides. Recent reports suggest the possibility that Bacteroides fragilis may cause diarrhea. Most of the bacteria listed are associated with contaminated water. Several of them, such as E. coli, may be transmitted via contaminated food or water. E. coli may invade tissue or may produce an exotoxin. Symptoms occur 10-12 hours after contact and consist of vomiting, nausea, cramps, diarrhea, chills, and fever. Salmonella or Shigella gastroenteritis is due to tissue infection by the organisms, although Shigella is capable of toxin production. Shigella dysentery symptoms ordinarily occur 36-48 hours after infection, but the time is variable. Salmonella gastroenteritis (due to species other than Salmonella typhi) is most frequently associated with ingestion of poultry, eggs and egg products, powdered milk, and fresh pork. Symptoms most often manifest in 8-48 hours, with an average onset at 24 hours. Symptoms of both Shigella and Salmonella gastroenteritis are similar to those of E. coli. Salmonella dysentery should be differentiated from typhoid and paratyphoid fever, which have considerably longer incubations and different emphasis in symptoms.

    Nonbacterial causes of diarrhea. There are other causes for food poisoning that do not involve bacterial agents. Some of these are ingestion of toxins from certain fish (e.g., ciguatera or scombroid fishes) or shellfish, and the Chinese restaurant syndrome (due to excess monosodium glutamate seasoning; however, at least one report disputes this etiology). Other causes for nonbacterial infectious diarrhea include viral infection (especially by rotavirus) and infection by the parasite Giardia lamblia. Ulcerative colitis and other conditions may also have to be considered.

    Differential diagnosis. Some differential points include incubation time and presence of fever, vomiting, or diarrhea. Incubation time less than 7 hours without fever suggests S. aureus or ingestion of the preformed toxin of B. cereus. Both of these usually are associated with vomiting, but S. aureus is more likely to cause diarrhea (about 75% of cases) than B. cereus (<40% of cases). Incubation of about 12 hours favors C. perfringens and B. cereus without preformed toxin; in both disorders toxin is formed after the organism is ingested rather than before. Symptoms of both are predominantly abdominal cramps and diarrhea, usually without fever or vomiting. Presence of neurologic symptoms suggests C. botulinum or chemical poisoning (mushrooms or fish toxins).

    Laboratory diagnosis. Includes stool culture and culture of possibly contaminated food or water. Diagnosis of C. botulinum or C. difficile infections usually requires demonstration of toxin, which was discussed earlier in the section on clostridia. Gram stain of the stool may be helpful in some patients. Patients with infection by bacteria that invade the mucosa of the GI tract tend to have WBCs in the stools, whereas those whose effect is produced by toxin usually do not. However, this is only a general rule. Many WBCs in the stool are typical of Shigella, Campylobacter, or C. difficile infection, although it also frequently occurs with Salmonella gastroenteritis, E. coli, Y. enterocolitica, or V. parahaemolyticus. Grossly visible blood in the stools is frequently found with Campylobacter, but gross blood may occasionally appear with severe infection by the other enteroinvasive bacteria, and microscopic blood is fairly frequent. Diagnosis of S. aureus or C. perfringens contamination usually necessitates culture of the affected food, since these organisms are considered normal stool flora.

    Traveler’s diarrhea. Diarrhea is common among visitors to many third-world countries; although it should be remembered that diarrhea may occur in persons who never leave the United States, and one half or more of the visitors to these countries (especially those on guided tours) do not get diarrhea. Several studies have shown that the most common cause for so-called traveler’s diarrhea in the majority of these countries is a subgroup of E. coli bacteria known as toxigenic E. coli. A much smaller number of persons develop diarrhea because of infection by other bacteria such as Salmonella, Shigella, and cholera vibrios; and by parasites such as Amoeba histolytica and Giardia lamblia. Infection by traveler’s diarrhea bacteria or by parasites most often is caused by use of water containing the organisms or food contaminated by the water.

    At present, there are three ways to control diarrhea: take precautions to avoid infection; take medicine to prevent infection (so-called prophylactic medication); or take medicine after diarrhea starts in order to quickly end the diarrhea.

    The best way to prevent traveler’s diarrhea is to avoid getting infected. This means avoiding local water unless there is no doubt that the water is safe. It is not advisable to take the word of the local people that the water is safe—it may be safe for them but not for visitors. Travelers must remember that local water may be present in ways they do not suspect; they should avoid ice, cocktails, drinks that need water or ice added, juice made from concentrate, and fresh salads with lettuce or ingredients that could have been washed. When tourists order orange juice they often cannot be certain it is 100% freshly squeezed from the fruit (even if a waiter says it is), so it is better to eat freshly cut fruit than to take a chance with the juice. It is also wise not to eat the outside skin of fruit (such as apples or pears) that could have been washed with local water. Alcohol—even 86 proof—may not sufficiently sterilize contaminated ice or water.

    Raw fish or shellfish (such as oysters or clams) can be contaminated by the bacteria that cause cholera. Raw or poorly cooked (“rare”) meat may be contaminated by different or even more dangerous organisms. Nonpasteurized milk is also dangerous, and it is usually hard to be certain whether local milk is pasteurized or not, especially if it is served already poured.

    There are ways to find safe water:

    1. Canned or bottled juices or colas are usually safe, as are drinks made with hot water (hot coffee, hot tea).
    2. Travelers can buy safe bottled water. The easiest and safest to find is mineral water. Mineral water with carbonation is available everywhere and is safe, because the carbonation does not permit bacteria to grow. However, some persons do not like the taste. Mineral water without carbonation (in Spanish, called “sin gas”) can be purchased in most places. This is generally safe if it comes from a sealed bottle, but it is harder to make certain whether the source of the water is pure. In many countries it is possible to purchase mineral water without gas in liter (quart) bottles in supermarkets (in Mexico, it is sold in pharmacies).
    3. Travelers can bring water purification tablets with them. There is a choice of chlorine or iodide; iodide is preferred because it will kill the parasite Giardia lamblia, whereas chlorine may not, if the amount of chlorine is not up to full strength. Both will kill bacteria. (Note: City water supplies in some cities of some countries may be chlorinated but not in sufficient strength.)
    4. Travelers may bring water purification filter equipment with them. The equipment should have a filter 0.45 microns or smaller hole size in order to be effective against E. coli. One easily portable, easily usable, and relatively inexpensive filtration system I have personally used is called “First Need Water Purifier.” It has a filter life of 800 pints, the filter can be replaced, and the apparatus including filter costs about $45.00. It can be obtained from REI Inc., P.O. Box C-88125, Seattle, WA 98188-0125, or from the manufacturer: General Ecology, Inc., 151 Sheree Blvd, Lionville, PA 19353.
    5. Travelers can boil local water. Three minutes boiling time (3 minutes starting from the time vigorous boiling and many large bubbles appear) is safe against bacteria. For locations at high altitudes, 5 minutes boiling time (or even longer at very high altitudes) is necessary.

    Travelers can take certain medicines to prevent infection, or before they get diarrhea (“prophylactic medication”). However, most experts do not recommend prophylactic medication, especially antibiotics, because the medicines may produce side effects in a small number of people.

    Travelers can take certain medications to stop diarrhea after it starts. Most cases of diarrhea are not life-threatening and will stop without medication in 2-3 days; therefore, some experts do not advise any treatment of mild or moderate diarrhea for the first 48 hours. However, it is not always possible to predict which cases will stop and which will become worse. The most commonly used medications are antidiarrheal preparations and antibiotics. These should not be used simultaneously. Some experts feel that antibiotics should not be used in cases of nausea and vomiting without diarrhea.

    Antidiarrheal medications include the following:

    1. Bismuth subsalicylate (trade name “Pepto-Bismol”). The dose is 1 ounce (30 ml) every 30 minutes until the diarrhea stops, but no more than 8 doses (8 ounces) within each 24-hour period. Take for 1-2 days.
    2. Loperamide (trade name “Imodium”). More experts prefer this medication than bismuth subsalicylate. Loperamide comes in 2-mg capsules. The usual dose is 2 capsules to begin with, then 1 capsule after each additional loose stool, up to a maximum of 8 capsules within each 24-hour period. At present, this is probably the best overall antidiarrheal medication.

    Travelers can take antibiotics to stop diarrhea caused by bacterial infection. Antibiotics would help E. coli infections, but would not cure Giardia infections. The most commonly recommended antibiotics are the following:

    1. Doxycycline. It is ordered in 100-mg capsules. The dose is one capsule twice a day for a total of 3-5 days. Doxycycline is a tetracycline antibiotic, and children under age 12 years may get very undesirable side effects.
    2. Trimethoprim-sulfamethoxazole (trade names “Bactrim” or “Septra”). It is ordered in double-strength tablets containing 160 mg of trimethoprim. The usual dose is one double-strength tablet twice a day for a total of 3-5 days. A few persons are allergic to the sulfa part of this antibiotic combination.
    3. Trimethoprim (without sulfa; trade name “Trimpex”). It is ordered in 100 mg tablets. The usual dose is 2 tablets twice each day for a total of 3-5 days. For persons with poor kidney function the dose is less; a physician should be consulted (the same warning is true for Trimethoprim-sulfa).
    4. Ciprofloxacin (trade name “Cipro”). This is ordered in 500 mg capsules. The dose is one capsule twice daily for 5 days. Results are reported to be as good as or better than results of Trimethoprim. Do not use in children or in pregnant or nursing women.

    Persons who already have severe disease (lung, heart, kidney, etc.) or who get severe diarrhea should see a physician rather than try to treat themselves.

  • Anaerobic Bacteria

    The three major sources of anaerobic organisms are the dental and mouth area, the lower intestinal tract (ileum and colon), and the female external genital tract (vagina and vulva area). Anaerobes comprise about 95% of the bacterial flora of the colon and outnumber aerobes in the mouth and vagina. From the mouth the organisms can reach the lungs and brain; from the vagina they may involve the remainder of the female genital tract; diseases of the lower intestinal tract may release anaerobes into the abdominal cavity; and all of these locations may be the source of organisms found in the bloodstream. In addition, anaerobic bacteria are frequently associated with chronic infection, such as bronchiectasis, abscess, or chronic osteomyelitis. Infections with anaerobes frequently are mixed infections that also contain aerobes. The types of infection most frequently associated with anaerobes are listed in the box below.

    Types of Infection Most Frequently Associated With Anaerobes (Alone or as a Mixed Infection)
    Dental or mouth area infection
    Chronic sinus infection
    Bite wounds
    Bronchiectasis and aspiration pneumonia
    Gynecologic intraabdominal and extra abdominal infection
    Abscess of any area other than skin; including brain, abdominal and thoracic cavities, and any organ
    Infections associated with the intestinal tract, especially the colon (diverticulitis, appendicitis, bowel perforation, etc.)
    Deep tissue infection or necrosis
    Biliary tract infection
    Chronic osteomyelitis

    Anaerobic infections usually center on three groups of organisms: Clostridia species, Bacteroides species, and the anaerobic streptococci.

    Clostridia

    These gram-positive anaerobic rods include several important organisms. Clostridium perfringens (Clostridium welchii) is the usual cause of gas gangrene. It is a normal inhabitant of the GI tract and reportedly can be isolated from the skin in about 20% of patients and from the vagina and female genitalia in about 5%. Therefore, just as with S. aureus, a culture report of C. perfringens isolated from an external wound does not necessarily mean that the organism is producing clinical infection. When isolated from abdominal or biliary tract infections, C. perfringens most often is part of a polymicrobial infection and, although serious, is not quite as alarming as isolation from a deep tissue wound. Clostridium perfringens occasionally is a cause of “food poisoning” (discussed later).

    Clostridium tetani causes tetanus. The organism can be found in the human GI tract but is more common in animals. Spores are widely distributed in soil. Clinical disease is produced by release of bacterial exotoxin after local infection in a manner analogous to diphtheria. Puncture-type wounds are notorious for high risk of C. tetani infection. The incubation time is 3-14 days in most patients, a few cases being reported as early as 24 hours after exposure. Cultures for C. tetani are said to be positive in less than 50% of patients. Clostridium difficile is the most frequent proven cause of antibiotic-associated diarrhea. In the 1950s and early 1960s, broad-spectrum oral antibiotics were frequently used, and S. aureus was thought to be the major cause of antibiotic-associated enteritis. Beginning in the late 1960s parenteral antibiotics became much more common in hospitals, and C. difficile was eventually proven to be the major etiology. Clostridium difficile enteritis usually occurs during or after therapy with antibiotics, although some patients have not received antibiotics. One report indicated a possible association with diarrhea induced by cancer chemotherapeutic agents. The condition may consist only of varying degrees of diarrhea, may progress to inflammation of portions of the colon mucosa, and in the more severe form (known as pseudomembraneouscolitis) there is inflammation and partial destruction of varying areas of the colon mucosa, with formation of a pseudomembrane of fibrin, necrotic cells, and segmented neutrophils on the surface of the remnants of the affected mucosa. Some patients develop intestinal perforation and sepsis.

    Diagnosis of C. difficile colitis is not always easy. Only about 25%-30% (range, 20%-33%) of diarrhea occurring with antibiotic therapy is due to C. difficile, with most of the remainder not associated with currently known infectious agents. Sigmoidoscopy or colonoscopy can be done to document pseudomembrane formation, but this procedure runs the risk of perforation; and even in pseudomembraneous enterocolitis (PMC), pseudomembranes can be demonstrated in only about 50% (range, 40%-80%) of patients. The patient stools in PMC typically contain WBCs and often contain red blood cells, but gross blood is uncommon. However, WBCs on Gram stain actually are present in only about 45%-50% of cases. For several years, culture was the usual means of diagnosis. Today, this is not often done. C. difficile can be cultured, with reliable results, only on special media, so diagnosis usually is made through detection of C. difficile cytotoxin. Stool specimens must be frozen and sent to a reference laboratory with dry ice. The specimen container must be sealed tightly since the carbon dioxide from the dry ice can inactivate the toxin. Another problem is the fact that C. difficile can be found in the stool of some clinically healthy persons, including 30%-40% (range, 11%-63%) of clinically healthy neonates, 10%-15% of children, 3% (range, 0%-10%) of adults, 20% (range, 11%-36%) of hospitalized persons without diarrhea and not taking antibiotics, and about 30% (range, 20%-46%) of patients taking antibiotics but without diarrhea. Even in patients with endoscopy-proven PMC, stool culture is positive for C. difficile in only about 90% (range, 75%-95%) of cases. Most laboratories today rely more on tests to detect C. difficile toxin, which has been shown to correlate much better with C. difficile clinical infection than does stool culture. There are several C. difficile toxins, of which the best characterized are called toxins A and B. Toxin B is a cytotoxin that must be detected by a tissue culture system with an incubation period of 48 hours. In endoscopy-proven PMC, toxin B sensitivity is reported to be about 90% (range, 64%-100%). Results may be positive in some patients with positive C. difficile cultures who are clinically normal, especially in infants. An enzyme immunoassay kit is commercially available that detects both toxin B and toxin A (Cytoclone A+B). Sensitivity reported to date is about 85%-90% (range, 76%-99%). Toxin A is an enterotoxin that originally was assayed with a biologic system, the rabbit ileal loop test. Several EIA tests are commercially available for toxin A, with reported sensitivity of about 85% (range, 65%-97%). There is a simple latex agglutination kit available (CDT or Culturette CDT) that can provide same-day results. This kit was originally thought to detect toxin A but subsequently was found to be detecting an enzyme (glutamate dehydrogenase) from C. difficile. The test detects non-toxin-producing as well as toxin-producing C. difficile and cross-reacts with Clostridium sporogenes and a few strains of other clostridia. Nevertheless, in various studies this test frequently gave results equivalent to those of the cytotoxicity test (about 75%-90%; range, 38%-97% positive in patients with proven PMC, with roughly 90% specificity). Another company has a similar test (Meritec-CD). In one comparison between CDT and Meritec-CD, Meritec-CD showed about 10% less sensitivity.

    Clostridium botulinus produces botulism. Botulism is a severe food poisoning due to ingestion of preformed botulinal endotoxin (a powerful neurotoxin) contained in the contaminated food, rather than actual infection of the patient by the organism. C. botulinum spores are widespread, but they can germinate only in anaerobic conditions at a fairly high pH (>4.6). These conditions are met in canned foods that have not been sufficiently heated during the canning process. Therefore, C. botulinum is usually associated with canned food, especially home canned. Vegetables are the most frequently involved home-canned food, but any variety of canned food may become contaminated. Fortunately, the disease is not common. Although the endotoxin is preformed, symptoms most often appear 12-36 hours after ingestion (in adult patients) and commonly include nausea, vomiting, and abdominal cramps (about 50% of patients), constipation (75%), cranial nerve signs of dysphagia, dysarthria, and dry mouth (80%-90%), upper or lower extremity weakness (70%), and diplopia or other eye abnormalities (90%). There is no fever or diarrhea. Differential diagnosis in adults includes Guillain-Barrй syndrome, drug reaction (especially phenothiazines), myasthenia gravis, cerebrovascular accident, chemical poisoning (mercury, arsenic, etc.), diphtheria, and tick bite paralysis (Landry’s ascending paralysis). Botulism may also occur in infants, usually between ages 3 and 26 weeks (median age 10 weeks). The classic syndrome is onset of constipation followed by 4-5 days of progressive feeding difficulty, ptosis, muscle hypotonia, and possibly respiratory distress. Mildly affected infants may have varying degrees of “failure to thrive” with feeding difficulty and mild muscle weakness, whereas severely affected infants may have severe respiratory distress. Some cases of sudden infant death syndrome (SIDS) have been ascribed to infant botulism, whereas some infants and older children (investigated during studies initiated by botulism cases) were found to harbor C. botulinum organisms without symptoms. Honey was incriminated in some cases as the source of infection but was not used in the majority of cases.

    Standard laboratory tests, including those on the CSF, are usually normal in botulism. Electromyography (EMG) may be helpful in differentiating adult botulism from certain other neurologic diseases, but the typical EMG findings are neither specific nor always present. The diagnosis is confirmed by stool culture and demonstration of C. botulinum toxin, neither of which can be done in the ordinary laboratory. In addition, food suspected of contamination should always be tested. Patient vomitus and gastric contents have also been tested. The basic specimens in adult botulism are stool (25 gm or more) and serum (at least 5 ml). For diagnosis of infant botulism a stool specimen is required; but infant serum rarely contains C. botulinum toxin and therefore infant serum specimens are not necessary. The specimens should be kept refrigerated, since the toxin is heat labile, and sent to a reference laboratory with a coolant (for short distances) or dry ice (for more than 1-day transit). There are several C. botulinum serotypes, but most cases are caused by types A and B, with type A predominating.

    Bacteroides

    Bacteroides are the most frequent organisms found in anaerobic infections. They comprise several species of gramegative rods normally found in the mouth, the intestine, and the female genital tract. Isolation of these organisms often raises the question of their significance or pathogenicity. It seems well established that bacteroides occasionally cause serious infection, which frequently results in abscess or gangrene. The most commonly associated clinical situations include septic abortion, aspiration pneumonia, focal lesions of the GI tract (e.g., carcinoma or appendicitis), and pelvic abscess in the female.

    Anaerobic streptococci

    Anaerobic streptococci are frequently associated with Bacteroides infection but may themselves produce disease. They are normally present in the mouth and GI tract. Septic abortion and superinfection of lesions in the perirectal area seem to be the most commonly associated factors. Anaerobic streptococci are also part of the fusiform bacteria-spirochetal synergistic disease known as Vincent’s angina.

    Laboratory diagnosis of anaerobic infections

    Anaerobic specimens cannot be processed by the laboratory as easily as those from aerobic infections. Anaerobic bacteria in general do not grow as readily as common aerobic bacteria, and prereduced media or other special media are often needed. Achieving and maintaining anaerobic culture conditions are not a simple matter. However, by far the greatest problem is the specimen received by the laboratory. If the specimen is not properly maintained in an anaerobic environment en route to the laboratory, the best and most elaborate facilities will be of little help. For abscesses or any fluid material, the preferred collection technique is to aspirate the material with a sterile syringe and needle, then expel the residual air from the needle by pushing the syringe plunger slightly, and then immediately cap the needle point with a sterile cork or other solid sterile material. The syringe must be transported immediately to the laboratory. If there is no liquid content, a swab that forms part of one of the special commercially available anaerobic transport systems should be used. Directions for creating the anaerobic environment should be followed exactly. A less satisfactory procedure is to inoculate a tube of thioglycollate medium immediately after the specimen is obtained and immediately recap the tube.