Articles on Medical Diseases and Conditions

Category: Bacterial Infectious Diseases (Including Chlamydia, Mycoplasma, and Legionella Infections)

Bacterial Infectious Diseases (Including Chlamydia, Mycoplasma, and Legionella Infections)

  • Antibiotic Removal

    One of the major frustrations in microbiology is the interference to bacterial growth caused by previous administration of antibiotics. Culture growth inhibition may occur even if the organism is not sensitive to the antibiotic. Several antibiotic removal devices are now available, based on membrane filtration or resin adsorption. These are useful for liquid specimens such as spinal fluid, body cavity fluid or blood. Although some evaluations have found these devices to be helpful, others have not. This technique was (and is) controversial among infectious disease specialists.

  • Serum Bacteriostatic or Bacteriocidal Concentration (Schlichter Test)

    In patients with bacterial endocarditis whose symptoms persist despite treatment, it is important to know whether antibiotic therapy really is effective in vivo. Also, some antibiotics, such as gentamicin, have a therapeutic range close to the toxic range. Blood levels of some antibiotics can be measured using various methods. This will provide some assurance that antibiotic blood levels have been reached that ordinarily should be effective. However, this does not guarantee that the organisms are in fact being sufficiently inhibited or killed. To estimate in vivo effectiveness, a Schlichter test may be performed. A patient blood specimen is obtained 15 minutes after IV infusion of the antibiotic (1 hour after an intramuscular dose). This represents the peak antibiotic level. If a trough level is desired, the specimen is drawn just before the next antibiotic dose is to be given. A standard suspension of the organisms previously cultured from the patient is placed in serial dilutions of patient serum and incubated overnight. If the lowest serum dilutions (i.e., those tubes with the least dilution of the antibiotic) do not inhibit growth of the organism, therapy is probably not effective. There is some dispute on which dilution level to use as the peak value cutoff for therapeutic effectiveness; Schlichter accepted 1:2, but currently the majority of investigators require 1:8. In fact, for a test that is widely used and relied on, there is a surprising amount of disagreement about many critical technical aspects, including whether to obtain peak or trough level or both and what their optimal values are; whether to make the patient serum dilutions with saline, Mueller-Hinton broth, nonantibiotic-containing serum, or a mixture of these; what criteria should define the bacteriocidal endpoint; and so forth. For this reason some investigators doubt the value of the test.

  • Antibiotic Sensitivity Procedures

    Disk diffusion method

    Antibiotic sensitivity testing is usually done using either the tube dilution or the agar diffusion (sometimes called “disk sensitivity”) technique. Of these, agar diffusion is by far the more common, and the Kirby-Bauer modification of this technique is the standard procedure. The Kirby-Bauer method involves (1) isolating a bacterial colony from its original growth medium, (2) allowing the bacteria to grow in a broth medium to a predetermined visual density, (3) covering the entirety of a Mueller-Hinton agar plate with the bacterial isolate, (4) placing antibiotic sensitivity disks at intervals on the surface, (5) incubating for 18-20 hours, (6) examining for clear areas around individual disks representing bacterial growth inhibition by the antibiotic-impregnated disk, and (7) measuring the diameter of these inhibition zones. Results are reported as resistant, sensitive, or intermediate, depending on previously established values for zone size based on tube dilution studies most often furnished by the disk manufacturer. Consistent results depend on strict adherence to good technique at each step, as well as the quality of the antibiotic disks and agar used. Variation in potency of antibiotic disks from different shipments and disk or agar deterioration during storage necessitate a good quality control program. The Kirby-Bauer technique has limitations. To be accurate, it can be used only when the bacterium to be tested is aerobic, nonfastidious, and grows rapidly (produces colonies within 24 hours) on the agar growth medium. Thus, it can be used for the Enterobacteriaciae, Pseudomonas organisms, and staphylococci. The Kirby-Bauer method can also be used with H. influenzae, N. gonorrheae, and S. pneumoniae, but a different agar medium is necessary.

    Most organisms, fortunately, may be classified as sensitive or resistant. Intermediate sensitivity is a controversial area. In general, many believe that intermediate zones should be considered resistant, although certain organisms, such as enterococci, may be exceptions. If a particular antibiotic with intermediate degree of inhibition is important in therapy, the sensitivity test should be repeated to rule out technical problems. It might be useful to have the sensitivity test performed by the tube dilution method, if available. Another subject of dispute is the need for sensitivity testing in bacteria that almost always are sensitive to certain antibiotics. Penicillin (PCN) sensitive organisms include group A aerobic streptococci, pneumococci, Neisseria organisms, and Corynebacterium diphtheriae. A few PCN resistant or partially resistant strains of pneumococci (about 3%; range, 0%-35%) are being reported, and PCN resistant gonococci (about 2%; range, 0%-6%) are beginning to appear in various areas. At present, many laboratories do not perform sensitivity studies routinely on these bacteria. An occasional laboratory problem is requests by physicians to include additional sensitivity disks in sensitivity panels. Only a limited number of disks can be spaced on a sensitivity agar plate, so that an additional disk either means that another antibiotic must be deleted or else an additional plate must be used at extra expense. In many cases the extra antibiotic requested has a similar sensitivity spectrum to one already on the panel. Laboratories frequently include only one representative of an antibiotic family in sensitivity panels because sensitivity differences among antibiotic family members (e.g., the various tetracyclines) are usually very minor.

    Serial dilution method. The other major test procedure is serial dilution (sometimes called “tube dilution”). A standardized concentration of the bacterium to be tested is placed in tubes or microtiter plate wells containing liquid culture medium. Serial dilutions of the antibiotic to be tested are added to consecutive tubes containing the bacterial suspension and the tubes are incubated, usually for 24 hours. The bacterial suspension is cloudy, and any tube in which the bacteria are sufficiently inhibited will become clear due to absence of bacterial multiplication. The last dilution tube (i.e., the tube with the highest degree of antibiotic dilution) that is clear (i.e., still shows acceptable bacterial inhibition) is reported as the minimal inhibitory concentration (MIC). This is defined as the smallest concentration of antibiotic that will inhibit bacterial growth. Therefore, the higher the antibiotic dilution before bacterial growth overcomes the effect of the antibiotic, the smaller the amount (concentration) of antibiotic necessary to inhibit the organisms. The MIC is actually reported in terms of the antibiotic concentration per milliliter of solution that is necessary to inhibit the bacteria (e.g., an MIC of 15 means a level or concentration of 15 µg of the antibiotic/ml of solution). To determine if the organism is sensitive or resistant to the antibiotic, one compares the MIC with the achievable blood level of antibiotic, which varies according to size of dose, frequency of dose, route of administration, and so forth. If the maximal achievable blood level of the antibiotic is less than the minimal concentration of the antibiotic necessary to inhibit the organism (the MIC), the antibiotic presumably will not be effective (or, to consider it in another way, the organism is resistant). In general, this means that the lower the MIC value, the more sensitive the organism is likely to be toward the antibiotic. The same tube dilution procedure is carried out for each antibiotic to be tested with each organism. As a general rule, an adequate serum antibiotic level should be at least two to four times the MIC to compensate for some of the clinical and laboratory variables.

    A relatively recent method is called the E test, that combines aspects of Kirby-Bauer with tube dilution MICs. Somewhat simplified, a single bacteria isolate is spread over the surface of a Mueller-Hinton type of agar plate (a few other media have been used experimentally for several special requirement bacteria). A rectangular plastic strip containing a continuous gradient of a single antibiotic along one side and an MIC scale with gradation representing twofold (doubling) dilutions of the antibiotic concentration along the other side is placed on the innoculated plate. After 24 hours of incubation (some have used shorter time periods), the point where a clear zone of bacterial suppression begins after the areas of bacterial growth is read from the MIC scale. More than one antibiotic-impregnated strip can be used at the same time, although the number is consideraly limited by the need to keep the strips far enough apart to prevent interference. Results have generally been reported to correlate 90%-95% with standard MIC results, although some organisms correlate in the 80%-90% range and not all organisms can be tested by this method.

    Disk method versus dilution method. There are certain advantages and disadvantages to each antibiotic sensitivity technique. The disk method is cheaper and easier than tube dilution if both are done manually. Semiautomated and fully automated equipment is available for tube dilution, but the cost of the equipment usually restricts this to larger or high-volume laboratories. The disk diffusion method can be used only for certain common, rapidly growing organisms. Tube dilution can be used with more organisms than disk diffusion, but many cannot be tested with either technique. Neither technique can be used for anaerobes, under usual conditions. The disks employed in the Kirby-Bauer disk sensitivity method contain antibiotic concentration based on serum antibiotic levels achieved with usual drug doses. In certain body tissues or body fluids such as urine, the concentration of the antibiotic may be considerably more or less than the serum concentration, and the disk sensitivity result may therefore be misleading. For example, the urine concentration of some antibiotics may be much greater than the serum concentration. Thus, the organism may not be inhibited by the disk (serum) antibiotic concentration but may actually be inhibited at the higher antibiotic concentration in urine. In this case, a disk sensitivity result showing the organism to be sensitive is correct, but a disk result showing the organism to be resistant may not be correct. The opposite could be true if infection took place in a location where the antibiotic concentration was considerably less than the level in serum. Another problem, of course, is that the disk sensitivity method uses a single concentration of antibiotic. The organism might be inhibited at a lower concentration than the disk contains. Even more important, the actual concentration of that antibiotic in the serum of any individual patient may be quite different from the disk concentration for a variety of reasons (differences in dosage, absorption, degradation, excretion rate, etc.).

    The tube dilution method shares some of the drawbacks of the disk diffusion method, the principal difficulty being that neither method takes into account the actual antibiotic concentration in patient serum or in the area of infection, these concentrations being unknown. However, the tube dilution method does have the advantage in that it roughly indicates the actual antibiotic concentration necessary to inhibit the organism. As noted previously, if one can learn the theoretical antibiotic concentration from a given dosage at the expected site of infection (in micrograms per milliliter), one can compare this with the level needed to inhibit the organism (the MIC, also reported in micrograms per milliliter) and have a better estimate of probable therapeutic effectiveness. However, this does not guarantee that the actual concentration of antibiotic at the site of infection is the same as the theoretical or experimental concentration. It is also possible to test the effects of antibiotic combinations using the tube dilution method; this is not possible with the Kirby-Bauer method. Finally, it is possible to obtain the minimal bactericidal concentration (MBC) using a modification of the tube dilution method. The MBC is the smallest concentration of the antibiotic necessary to kill at least 99.9% of the bacteria. This may or may not require a higher concentration of antibiotic than the MIC and might be useful information if the patient’s theoretical or actual antibiotic blood level is higher than that required by the MIC but the patient is not responding to therapy.

    Bacterial resistance: beta-lactamase. Certain antibiotics, notably penicillin and the cephalosporins, have a certain structural area containing a nitrogen atom known as a beta-lactam ring. A group of bacterial enzymes (of which penicillinase was the first to be recognized) can split the beta-lactam ring and destroy the antibacterial activity of the molecule. These bacterial enzymes are now collectively called beta-lactamase. Certain tests have been devised to demonstrate bacterial production of beta-lactamase. There is considerable variation in the technical details of these tests and some variation in accuracy. Most, however, can be done in less than 1 hour and are reasonably accurate, possibly more so when indicating a positive reaction. A positive beta-lactamase test result suggests that the organism should be considered resistant to penicillin, ampicillin, and the first- and second-generation cephalosporins until results of antibiotic sensitivity studies are available. The test is particularly important in H. influenzae type B infection; up to 20%-30% (range, 6%-38%, depending on geographical location) have been reported to produce beta-lactamase. Staphylococcus aureus or epidermidas are even more likely to produce beta-lactamase, so much so that resistance to penicillin is usually taken for granted pending sensitivity study results. N. gonorrheae may produce beta-lactamase but is usually not tested for this except under special circumstances. Other antibiotic resistance mechanisms also exist.

    Methacillin-resistant S. aureus (MRSA) is not only a therapeutic problem but also presents difficulties in susceptibility testing. Standard susceptibility protocols will not demonstrate methacillin resistance in a significant minority of these organisms. There are certain changes in temperature and length of incubation, salt content of the media, and density of the bacterial inoculum that will provide the greatest rate of detection. Many laboratories do not use some or any of these recommended changes. Some antibiotics, such as certain cephalosporins, may sometimes appear to be effective against MRSA by in vitro sensitivity tests, whereas they will usually not be effective if given to the patient.

  • Nosocomial Infections

    A nosocomial infection is one that is acquired in a hospital. This subject is extremely important but cannot be covered in detail in a book that concentrates on laboratory tests. The most common cause of nosocomial infection is the indwelling urinary catheter. Some other important factors are surgery, long-term indwelling vascular catheters or equipment, conditions that depress patient resistance to infection, malnutrition, severe trauma or burns, overuse of antibiotics, and instrumentation of the urinary tract or other areas.

  • Intraabdominal Abscess

    Intraabdominal abscess is a recurrent problem that deserves attention. Some use the term “subphrenic” synonymously with intraabdominal, although most use the term subphrenic to refer only to abscess just below the diaphragm. The most common etiologies are postoperative complications of biliary tract or peptic ulcer surgery, penetrating abdominal trauma, and perforated appendix. Some 80%-90% of cases occur intraperitoneally. The spaces above and below the liver are the most common locations. About 25% of abscesses are located on the left side. The percentage of multiple abscesses ranges from 5%-40%. Bacteroides, E. coli, S. aureus, and streptococci are the most frequent organisms.

    X-ray film shows pleural effusion in about 60%-80% of cases (range, 43%-89%), elevated diaphragm in about 70% (range, 34%-82%), and gas in the abscess in about 25%-50% (range, 9%-61%). Atelectasis and pneumonia are frequent in the closest lung base.

    Computerized tomography (CT), gallium radioisotope scanning, and B-mode gray scale ultrasound may assist in diagnosis and localization of intraabdominal abscess. Of these, CT is probably the most sensitive, with approximately 90%-93% success rate (literature range, 82%-99%). Gallium 67 scanning has about 85% overall sensitivity (literature range, 75%-95%). The great advantage of gallium is total body scan capability with detection of inflammatory lesions located anyplace in the body (e.g., dental abscess, acute cholecystitis, or arthritis and osteomyelitis) rather than only intraabdominal infection when the scan is ordered for suspicion of intraabdominal abscess. There are major disadvantages, however. Gallium is excreted in the feces beginning about 12 hours after injection, so that bowel cleansing by laxatives and enemas (similar to barium enema preparation) is necessary and may have to be repeated. Scanning is usually performed 48 hours after injection, and the scan may have to be repeated if residual isotope is detected in the colon. This means that the study may take several days to complete. A certain percentage of various tumors may concentrate gallium and simulate abscess. There is normal uptake of isotope by the skeleton, liver, and spleen. B-mode gray scale ultrasound also has about 85% accuracy in detection of abdominal abscess and is less expensive than CT or gallium scanning. However, ultrasound in general gives better results in examining relatively small areas than in screening the entire abdomen. Ribs and air within the intestines may interfere.

  • Pneumonia

    The word pneumonia means inflammation of the lung. Although this could result from noninfectious sources (e.g., a chemical inflammation secondary to aspiration), the great majority of cases are due to bacterial or nonbacterial infectious agents. Almost any bacterium, many species of fungi, and many viruses could be associated with pneumonia under some circumstances. Except for the newborn, in the early pediatric age group viruses are the most common etiology, followed by Staphylococcus infections. In older children and young adults, viruses still markedly predominate, but pneumonococci become more prevalent. In middle-aged and older adults, pneumococci are the most frequent bacteria and H. influenzae is also important, although viruses still are more frequent numerically. Mycoplasma pneumoniae is a very important cause of pneumonia in older children, young adults, and middle-aged adults but may appear at any age. In debilitated persons, alcoholics, persons with depressed immunologic defenses, and the elderly, pneumococci are still very important, but other bacteria become much more common, especially Staphylococcus and Klebsiella. Staphylococcal pneumonia is particularly likely to occur following a viral pneumonia, such as influenza. Legionella infections are assuming more importance in adults and the elderly, although their true incidence is not known because Legionella is not tested for routinely.

    The most important nonbacterial agents producing lung infection are the respiratory-syncytial virus, influenza virus, the Aspergillus fungus, and an organism classified as a parasite, Pneumocystis carinii. Diseases caused by viruses, fungi, and parasites are discussed in other chapters.

  • 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.

  • Infective Endocarditis

    Endocarditis is infection of one or more heart valves, although infection of mural thrombi is usually included. The disease used to be separated into two types, acute and subacute. The acute type was most often caused by S. aureus, usually affected a normal heart valve, and had a relatively short severe course. Other bacteria less frequently associated with acute endocarditis were Streptococcus pyogenes, Streptococcus pneumoniae, and Neisseria gonorrheae. The subacute type was most often caused by streptococci of the viridans group with the enterococci next in frequency, usually involved previously abnormal heart valves, and had a relatively protracted course of varying severity. However, there is considerable overlap of clinical symptoms and severity of disease between the acute and subacute groups, and infections that would fit into the acute group may occur on previously abnormal heart valves. Therefore, many experts now include both types of endocarditis within one term, infective endocarditis.

    Predisposing conditions. Certain conditions predispose to infection of normal heart valves. Some examples are IV injection of drugs by drug abusers, indwelling vascular catheters or other devices, major surgical operations, and factors that decrease immunologic resistance. Conditions that create abnormal heart valves are congenital heart disease, rheumatic fever, atherosclerotic valve lesions, prosthetic heart valves, mitral valve prolapse, and nonbacterial valve thrombi. In addition to the same conditions that predispose to infection of normal valves, dental operations and urinary tract manipulation frequently precede development of infection on already abnormal valves.

    Organisms associated with endocarditis. Almost every pathogenic (and many relatively non-pathogenic) bacterium has been reported to cause infective endocarditis. Streptococci are the most frequent organisms (about 60%, range 50%-83%), with viridans group streptococci accounting for about 35% of all cases (range, 30%-52%); group D streptococci about 20%, and enterococci about 12% (range, 5%-20%). Staphylococcus aureus is isolated in about 20%-25% (range, 9%-33%) of cases. Coagulaseegative staphylococci are seen more frequently in association with intravascular catheters. When the patient has decreased resistance to infection (refer to the box), fungi and bacteria that ordinarily are considered uncommonly pathogenic or nonpathogenic may become involved.

    Clinical findings. Infective endocarditis falls about halfway between bacteremia and septicemia. Bacteria grow in localized areas on damaged heart valves and seed the peripheral blood; this may be infrequent, intermittent, or relatively continuous, with gradations between the two extremes. Classic signs and symptoms include fever, heart murmurs, petechial hemorrhages in the conjunctivae, small “splinter hemorrhages” in the fingernail beds, and splenomegaly. Hematuria is very frequent, and red blood cell (RBC) casts are a common and very suggestive finding. There often (but not always) is a normocytic and normochromic anemia. Leukocytosis is often present, but it too may be absent. Signs and symptoms are variable among individual patients, and the diagnostic problem is often that of a fever of unknown origin.

    Conditions Associated with Increased Rate of Infection or Infection by Unusual or Resistant Organisms
    GENERAL CONDITIONS
    Human immunodeficiency virus infection (e.g., AIDS)
    Diabetes mellitus (poorly controlled)
    Uremia
    Alcoholism
    Trauma (severe)
    Burns (extensive or severe)
    Malnutrition
    Very young or very old age
    THERAPY ASSOCIATED
    Adrenocorticosteroid therapy
    Immunosuppressant therapy
    Chemotherapy of tumors
    Antibiotic therapy (inappropriate or broad-spectrum)
    MALIGNANCY
    Myeloma
    Leukemia and lymphomas
    Widespread nonhematologic malignancies
    INSTRUMENTATION
    Indwelling urinary catheters
    Indwelling vascular catheters

    Diagnosis of infective endocarditis and identification of the organism involved are made through blood cultures. The clinical picture, evidence of abnormal heart valves, and the organism that is isolated (e.g., S. viridans) are major considerations in differentiating endocarditis from bacteremia and septicemia. However, in spite of the fact that viridans and group D streptococci together cause about 50%-60% of infective endocarditis, a few investigators state that when these organisms are isolated from blood culture, they are actually contaminants (or are not responsible for clinically significant disease) in 75% or more of the isolates. Blood culture methods used for diagnosis of infective endocarditis are the same as those used for septicemia.

    Blood cultures. Many physicians draw one specimen from each of two different sites (“one culture set”) to increase total sample volume and to help decide whether certain organisms are more likely contaminants (e.g., S. epidermidis in only 1 of 2 specimens). One must avoid contamination by skin bacteria by aseptic technique; that is, cleansing the skin with alcohol, then with iodine or an iodophore like Betadine, which has the most efficient bactericidal effect of the common antiseptics available. It is then removed by alcohol. Since alcohol inactivates iodophores, the iodophore must remain on the skin a minimum of 1 minute, then it is removed by alcohol. Some obtain the blood culture before removing the iodophore or iodine tincture preparation. Alcohol requires at least 2 minutes contact time to be effective. Several reports emphasize the need for adequate quantities of blood per bottle (at least 5 ml and preferably 10 ml) to maximize bacterial recovery rate. The optimum specimen quantity depends on the amount of diluting medium and the presence or absence of certain additives, such as sodium polyanetholsulfonate (Liquoid). Repeated blood cultures are even more necessary in possible endocarditis than in diagnosis of septicemia because of the often intermittent nature of the blood involvement; avoidance of culture contamination becomes even more important. About 15% of patients (literature range, 2.5%-64%) do not have positive blood cultures. Uremia is especially apt to be associated with negative cultures.

    False negative blood cultures. Some possible reasons for false negative blood cultures include recent antibiotic therapy, insufficient blood obtained for the amount of culture media, use of culture media unsuitable for anaerobes or for bacteria with special growth requirements, slowly growing organisms not detected during usual examination periods, various technical laboratory problems (specimens not obtained at optimal times), and combinations of these factors. One of the most important problems is insufficient blood specimen, especially when the number of organisms is small. Most investigators consider a 1:10 ratio of blood to culture medium to be optimal, and some insist on a minimum of 10 ml of blood (in adults) instead of the usual 5 ml. As noted previously, the optimal amount of specimen depends on the amount of diluting medium and the type of culture medium and system. There have been many blood culture systems advocated: use of many different media, vented and unvented containers, different anticoagulants and additives, hypertonic glucose media, filter or radioisotope detection equipment, and so forth. Interestingly, no system has consistently detected all bacteria all of the time. When two or more culture systems are compared, each system almost invariably detects a certain percentage of organisms that the others miss although some systems provide overall better results than others.

    Nutritionally deficient streptococci. Occasional patients are infected by streptococci that grow in blood culture media but not on media used to subculture and identify the organisms. This could lead to a false impression of a negative culture. These streptococci are nutritionally deficient (not all in the same nutrient) and will grow on subculture media that are supplemented with the nutrients (e.g., pyridoxine) that they need. They usually grow as satellites around colonies of staphylococci, much as H. influenzae does.

  • Septicemia and Bacteremia

    The concept of septicemia should probably be separated from that of bacteremia, although in many studies the two are not clearly separated. In bacteremia, a few bacteria from a focal area of infection escape from time to time into the peripheral blood. However, the main focus remains localized, and symptoms are primarily those that are caused by infection in the particular organ or tissues involved. Bacteremia may occur without infection following certain procedures, such as dental extraction (18%-85%), periodontal surgery (32%-88%), tooth brushing (0%-26%), bronchoscopy (15%), tonsillectomy (28%-38%), upper GI endoscopy (8%-12%), sigmoidoscopy (0%-10%), urethral dilatation (18%-33%), cystoscopy (0%-17%), and prostate transurethral resection (12%-46%). In one representative series, E. coli was isolated in about 20% of patients with bacteremia; S. aureus, 10%; and Klebsiella, pneumococcus, Streptococcus viridans, Bacteroides, and Pseudomonas, about 6% each. The percentage of S. epidermidis isolated varies greatly (3%-34%), probably depending on how many were considered contaminants. Polymicrobial bacteremia is reported in about 7% of cases (range, 0.7%-17%). In septicemia there is widespread and relatively continuous peripheral blood involvement. The characteristic symptoms are systemic, such as marked weakness and shock or near shock. Shock has been reported in 16%-44% of patients with gramegative bacteremia. These symptoms are usually accompanied by high fever and leukocytosis. However, septic patients may be afebrile in 10% (range, 4%-18%) of cases. Leukocytosis occurs in 60%-65% of patients (range, 42%-76%), leukopenia in 10% (range, 7%–17%), bands increased in 70%-75% (range, 62%-84%), and total neutrophils are increased in about 75% (range, 66%-92%). Any bacteria may cause septicemia. More than 50% of cases are due to gramegative rod organisms, with E. coli being the most frequent. Staphylococcus aureus probably is next most common. (In one literature review of seven studies of sepsis published in 1990 and 1991, four studies had predominance of gramegative organisms and three had predominance of gram-positive. In four of the seven studies, the percentage of gramegative and gram-positive organisms was within 10% of each other). The portal of entry of the gramegative organisms is usually from previous urinary tract infection. Many cases of septicemia follow surgery or instrumentation. The source of Staphylococcus septicemia is often very difficult to trace, even at autopsy. However, pneumonia and skin infections (sometimes very small) are the most frequent findings.

    Diagnosis. Blood cultures are the mainstay of bacteremia or septicemia diagnosis. Strict aseptic technique must be used when cultures are obtained, since contamination from skin bacteria may give false or confusing results. In cases of bacteremia or in septicemia with spiking fever, the best time to draw blood cultures is just before or at the rise in temperature. Three culture sets, one drawn every 3 hours, are a reasonable compromise among the widely diverging recommendations in the literature.

    Antibiotics and blood cultures. Blood should be drawn for culture before antibiotic therapy is begun, although a substantial number of cultures are positive despite antibiotics. Certain antibiotic removal devices are commercially available that can be of considerable help in these patients. It is essential that the culture request contain the information that antibiotics have been given, unless they have been stopped for more than 1 week. If penicillin has been used, some laboratories add the antipenicillin enzyme penicillinase to the culture medium. However, others believe that penicillinase is of little value and might actually be a potential source of contamination.

  • General Concepts in Bacterial Infection

    The main systemic signs and symptoms of severe bacterial infection are fever and weakness. The most characteristic laboratory finding is leukocytosis, with an increase in number and immaturity of the neutrophils. However, in proven infection sometimes leukocytosis may be minimal or even absent, and occasionally fever may be minimal or may not be present (page 59). This is not frequent but happens more often in infants and the elderly. It also happens more frequently in debilitated persons, especially those with other severe diseases that may impair the ability of the body to respond normally to infection. Overwhelming infection (e.g., massive pneumonia or septicemia) may have normal WBC count or even leukopenia.