Enteric bacilli form a large family of gramegative rods (see Table 37-6). As their name implies, most are found primarily in the intestinal tract. These include species such as Salmonella, Shigella, Escherichia coli, Enterobacter, Klebsiella, Proteus, and several others (see Table 37-6). Many are normal inhabitants and cause disease only if they escape to other locations or if certain pathogenic types overgrow; others are introduced from contaminated food or water. Salmonellae and shigellae are not normal gastrointestinal inhabitants and always indicate a source of infection from the environment.

Salmonella

These organisms cause several clinical syndromes. Typhoid fever is produced by Salmonella typhi (Salmonella typhosa). The classic symptoms are a rising fever during the first week, a plateau at 103°F-104°F (39.4°C-40.0°C) for the second week, then a slow fall during the third week, plus GI symptoms and splenomegaly. Despite fever, the pulse rate tends to be slow (bradycardia). This picture is often not present in its entirety. Diarrhea occurs in 30%-60% of patients. There typically is mild leukopenia with lymphocytosis and monocytosis. However, in one series only 10% of patients had leukopenia and 7% had a WBC count more than 15,000/mm3.

Laboratory diagnosis. During the first and second weeks of illness, blood cultures are the best means of diagnosis; thereafter, the incidence of positive specimens declines rapidly. During the latter part of the second week to the early part of the fourth week, stool cultures are the most valuable source of diagnosis. However, stool cultures may occasionally be positive in the first week; in carriers, positive stool cultures may persist for long periods. (About 3%-5% of typhoid patients become carriers—persons with chronic subclinical infection.) Urine cultures may be done during the third and fourth weeks but are not very effective. Even with maximum yield, blood cultures miss at least 20% of cases, stool cultures miss at least 25%, and urine cultures miss at least 75%. Repeated cultures increase the chance of diagnosis. Besides cultures, serologic tests may be performed. There are three major antigens in S. typhi: the H (flagellar), O (somatic), and Vi (capsule or envelope) antigens. Antibody titers against these antigens constitute the Widal test. Most authorities agree that of the three antibodies, only that against the O antigen is meaningful for diagnosis. Vaccination causes a marked increase in the anti-H antibodies; the level of anti-O antibodies rises to a lesser degree and returns much more quickly to normal. The Widal test (anti-O) antibodies begin to appear 7-10 days after onset of illness. The highest percentage of positive test results is reported to be in the third and fourth weeks. As with any serologic test, a fourfold (change of at least two dilution levels) rising titer is more significant than a single determination. There has been considerable controversy over the usefulness of the Widal test in the diagnosis of Salmonella infections. It seems to have definite but limited usefulness. Drawbacks to the Widal test include the following: (1) antibodies do not develop early in the illness and may be suppressed by antibiotic therapy; (2) antibody behavioris often variable and often does not correlate with the severity of the clinical picture; (3) an appreciable number of cases (15% or more) do not have a significantly elevated anti-O titer, especially if only one determination is done. Only about 50% (one study obtained only 22%) display a fourfold rise in titer. In some cases, therapy may suppress the response. A normal Widal titer is 0-1:40.

To summarize, in typhoid fever, blood cultures during the first and second weeks and stool cultures during the second, third, and fourth weeks are the diagnostic tests of choice. The Widal test may occasionally be helpful. Negative diagnostic test results do not exclude the diagnosis.

Paratyphoid fever (enteric fever) is produced by salmonellae other than S. typhi; the clinical picture is similar to typhoid fever but milder. Salmonella typhimurium and Salmonella enteritidis (formerly Salmonella paratyphi) are usually the most common causes in the United States. Diagnosis is similar to that for typhoid fever.

In the United States, Salmonella gastroenteritis is more frequent than typhoid fever or enteric fever. The gastroenteritis syndrome has a short incubation, features abdominal pain, nausea, and diarrhea, and is most commonly produced by S. typhimurium. There is usually leukocytosis with a minimal increase in neutrophils, in contrast to the leukopenia in textbook cases of typhoid fever. Blood cultures are said to be negative; stool cultures are usually positive.

Other salmonella diseases. Septicemia may occasionally be found, and salmonellae may rarely cause focal infection in various organs, resulting in pneumonia, meningitis, and endocarditis. Salmonella osteomyelitis has been associated with sickle cell anemia. Salmonella bacteremia is relatively frequent in patients with systemic lupus erythematosis. Salmonella infections, including bacteremia, are also more frequent in the acquired immunodeficiency syndrome (AIDS) and in patients with leukemia or lymphoma.

Sources of salmonella infection. Salmonella typhi is found only in humans, and infection is transmitted through fecal contamination of food and water. Other salmonellae infect poultry and animals. Nontyphoid salmonellosis is most commonly acquired from poultry and eggs, which in turn are most frequently associated with S. enteritidis infection. It is necessary to cook an egg thoroughly to avoid S. enteritidis infection, even when the eggshell has no evidence of being cracked. However, Centers for Disease Control (CDC) reports that one third of egg-related S. enteritidis infections took place when eggs had been cooked at recommended time and temperature. Only when cooking causes all of the egg yolk to become solid will the egg become safe. Pasteurized eggs are another option. Contaminated meat and nonpasteurized or powdered milk have been an occasional problem. Reptiles are reported to carry Salmonella species in 36%-84% of those cultured.

Due to DNA hybridization and other research work, the genus Salmonella is being reorganized to include certain organisms, such as Arizona, that previously were not considered salmonellae. The organisms previously considered Salmonella species are now serotypes (serovars) of the subspecies choleraesuis from the species Salmonella choleraesuis. The other organisms, such as Arizona, form part of other subspecies of S. choleraesuis.

Shigella

The shigellae are also important sources of intestinal infection as well as the salmonellae. Shigella organisms cause so-called bacillary dysentery. Shigellae usually remain localized to the colon and do not enter the peripheral blood; blood cultures are therefore negative, in contrast to blood cultures in early Salmonella infection. Stool culture is the main diagnostic test. Besides salmonellae and shigellae, certain other bacteria (e.g., Yersinia enterocolitica, Campylobacter jejuni, Clostridium difficile, and enteropathogenic E. coli) may cause diarrhea from GI infection; these are discussed elsewhere.

Enterobacter and Klebsiella

These bacteria are normal GI tract inhabitants. Nomenclature has been particularly confusing in relation to these organisms. Enterobacter was formerly called Aerobacter. Enterobacter and Klebsiella react differently to certain test media but are similar enough that previous classifications included both in the same group. According to previous custom, if infection by these organisms was in the lungs it was called Klebsiella; if it was in the urinary tract, it was called Aerobacter. Current classification does not make this distinction. The species of Klebsiella called Klebsiella pneumoniae is the organism that produces so-called Friedlьnder’s pneumonia, a resistant necrotizing pneumonia that often cavitates and that is characteristically found in alcoholics and debilitated patients. Klebsiella pneumoniae also is an important cause (about 10%) of both community-acquired and hospital-acquired urinary tract infection. The species of Enterobacter called Enterobacter aerogenes is an important agent (about 5%) in nosocomial urinary tract infections, is often resistant to therapy, and occasionally produces septicemia.

Present classification differentiates Enterobacter from Klebsiella. Sources of confusion include the family name Enterobacteriaceae, which is similar to the name of one component genus, Enterobacter. Enterobacteriaceae is a group of several tribes, each of which contains a genus or genera. One tribe, Klebsiellae, has a similar name to one of its three component genera, Klebsiella, and also includes the genus Enterobacter. A further source of difficulty is that the predominant species of Klebsiella is K. pneumoniae, which, despite its name, is found more frequently in the urinary tract than in the lungs.

Escherichia

Escherichia coli is the most common cause of community-acquired (about 70%) and of hospital-acquired urinary tract infection (about 50%). E. coli is likewise the most common cause of gramegative bacteremia or septicemia, both of community-acquired or hospital-acquired origin. The primary site of infection leading to bloodstream entry is most often the urinary tract, as happens with the majority of the gramegative rod bacteria. This is more frequent with urinary tract obstruction. E. coli is one of the most common causes of severe infection in the newborn, especially meningitis. E. coli causes periodic outbreaks of epidemic diarrhea in newborns and infants. E. coli has been incriminated as an important cause of traveler’s diarrhea, which may affect U.S. tourists in other countries. E. coli is a normal inhabitant of the colon, so a stool culture growing E. coli does not prove that the organism is the causative agent of diarrhea.

In the past it was thought that only certain strains of E. coli were responsible for diarrhea, and that serotyping (using antisera against the so-called enteropathogenic strains) was helpful in deciding whether or not E. coli was responsible for diarrhea by demonstrating or excluding the presence of the enteropathogenic subspecies (see Table 37-9). However, so many exceptions have been noted that serotyping is no longer advocated except as an epidemiologic tool to show that patients in an epidemic are infected by the same E. coli strain. Nevertheless, there is a condition caused by a specific strain of E. coli (0157:H7) called hemorrhagic colitis, manifested by severe diarrhea with abdominal pain and bloody stools. In the United States this organism predominately exists by colonizing cattle (10%-20% prevalence rate). Diarrhea in humans is caused by production of a verotoxin. Although bloody diarrhea is the organism’s trademark, about 30% of cases are said to have diarrhea without blood. Stools usually do not contain many WBCs. About 10%-30% of patients need hospitalization and 2%-7% develop the hemolytic-uremic syndrome (hemolytic anemia with red blood cell [RBC] fragmentation, thrombocytopenia, and renal failure). Diagnosis can be made by using selective media for E. coli 0157-H7 strain such as sorbitol-MacConkey agar (SMA), by fluorescent antibody stains applied to stool smears, or by verotoxin assay. In one study, verotoxin assay was 20% more sensitive than culture.

Proteus

This is a group of gramegative rods that assumes most importance as the cause of urinary tract infection in hospitalized patients (about 5%) but occasionally causes community-acquired cystitis and some cases of hospital-acquired bacteremia and other infections.

Yersinia

The genus Yersinia, which includes several organisms formerly located in the genus Pasteurella, contains three important species: Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica. Yersiniapestis is the cause of plague, which was transmitted historically by rat fleas, followed in some cases by nasopharyngeal droplet dissemination from infected humans. Today, plague is not a serious menace in Western nations, although a few cases in rodents (including prairie dogs) are reported each year from the American West and Southwest, from which source the disease is occasionally transmitted to humans. There are three clinical forms: septicemic, bubonic, and pneumonic. The septicemic type is responsible for 5%-10% of cases and is associated with a bacteremic form of febrile illness that progresses to septicemia and shock. Diagnosis is made by blood culture. When lymph nodes are primarily involved, the condition is known as bubonic plague. This constitutes the great majority of plague cases. However, septicemia or pneumonia may develop. Only one group of lymph nodes is enlarged in the majority of cases.

Diagnosis is made by blood culture (positive in about 80% of cases) or lymph node aspiration and culture (positive in about 80% of cases). Pneumonic plague has been uncommon in recent years and is rapidly fatal. Blood culture and sputum culture provide the diagnosis. Y. pestis grows on ordinary laboratory culture media.

Yersinia pseudotuberculosis is found in many wild and domestic animals and in various domestic fowl. Human infection is uncommon, or at least, is uncommonly recognized, and most often consists of mesenteric adenitis. There usually is abdominal pain, fever, and leukocytosis, a clinical picture that simulates acute appendicitis. Diagnosis is made by culture of affected lymph nodes (lymph nodes are likely to be placed in chemical fixative for microscopic examination, which makes culture impossible unless the surgeon orders a culture to be performed and directs personnel not to fix the specimen).

Yersinia enterocolitica is by far the most common pathogen of these three Yersinia species. Y. enterocolitica most often produces acute enteritis, with clinical features including headache, fever, malaise, crampy abdominal pain, and nonbloody diarrhea. The organism also can produce mesenteric adenitis and, rarely, intraabdominal abscess or septicemia. Enteritis is more common in children and mesenteric adenitis in adolescents and adults. Diagnosis is made by stool culture in patients with enteritis and by lymph node culture in those with mesenteric adenitis. Culture is less reliable for Y. enterocolitica than for the other yersiniae, because the organism grows somewhat slowly and forms tiny pinpoint colonies on ordinary media used for gramegative rods, which can easily be overlooked among normal stool organism colonies. The organism grows much better at room temperature (25°C) than at the usual incubation temperature of 37°C. Some investigators believe that “cold enrichment” is necessary (special media incubated at 4°C for several weeks). Therefore Y. enterocolitica will usually be missed on routine culture unless the laboratory takes special precautions.

“Opportunistic” enterobacteriaceae

There are a considerable number of species located in various genera of the Enterobacteriaceae that are less common pathogens. It was originally thought that these organisms were nonpathogenic or rarely pathogenic and that their importance was only in the necessity for differentiation from more pathogenic enteric organisms such as Salmonella. Now, however, it is recognized that these organisms produce disease, most often urinary tract infections but also septicemia and pulmonary infections, although the frequency of infection for any individual species is not high. Most of these organisms have been renamed and reclassified since initial studies were done. Some of the more important organisms include Arizona, Providentia (formerly Proteus inconstans and Proteus rettgeri), Citrobacter (formerly Bethesda group and Escherichia freundii), and Serratia. Infections caused by these organisms are often associated with decreased host resistance and with long-term bladder catheterization. Serratia is usually considered the most dangerous of these organisms. About 90% of Serratia infections involve the urinary tract, the great majority following urinary tract surgery or cystoscopy or associated with indwelling catheters. As many as 50% of Serratia urinary tract infections are asymptomatic. Bacteremia develops in about 10%. A few patients develop Serratia pneumonia, although respiratory tract colonization is much more frequent than pneumonia. The most common (but not the only) means of Serratia spread from patient to patient is the hands of hospital personnel.