Aerococci are distributed worldwide as contaminants of air and dust. They have been found also on meats, in raw vegetables, and on human skin in small numbers. In most circumstances, aerococci are saprophytic. Aerococci have been cultured from all areas of hospitals, including operating suites and delivery rooms. Disease in humans is distinctly uncommon. A. viridans can be isolated from 0.9% of patients with pneumonia. Most affected patients are elderly, but pediatric infections have been reported. Immunocompromised patients, particularly those with neutropenia, are at risk of developing infection. Adhesion factors may play a role. Additional information about the clinical manifestations, diagnosis, and treatment of infections caused by aerococci is presented in Box 183.1.

Commonly, Leuconostoc species are found on plants, especially sugar cane and leafy vegetables. They also are found in dairy products and wine. They are used in industry as starter cultures in food production. Although not a part of the normal human flora, occasionally they are recovered from vaginal swabs in healthy individuals. Leuconostoc rarely is pathogenic. Studies also have shown colonization of mucosal surfaces in some hospitalized individuals. Case reports of human infection began to appear in 1985. Risk factors are thought to include underlying disease states or immune compromise, gastrointestinal tract disease, prior or current antibiotic therapy (especially vancomycin), venous or gastrointestinal tract access devices, recent invasive procedures, and infancy. Of the first 21 cases reported in the English-language literature, 12 were in children, and 10 of those were in patients younger than 1 year of age. Documented portals of entry include central lines and gastrostomy tubes.

Bacteremia is by far the most common clinical manifestation of Leuconostoc infection, heralded by fever and usually
leukocytosis. Gastrointestinal disturbances, especially diarrhea, are common occurrences. Infants are prone to emesis. Pneumonia, dental infections, peritonitis, ventriculoperitoneal shunt infection, and meningitis also have been described.

Usually, cultures are positive within 24 to 48 hours. Leuconostoc species are somewhat fastidious. All are intrinsically vancomycin resistant. The identification of vancomycin-resistant streptococci should raise suspicion of Leuconostoc infection and prompt further biochemical studies. Usually, Leuconostoc is sensitive to the primitive beta-lactam antibiotics, especially penicillin and ampicillin. Tolerance to penicillin is fairly common; treatment with relatively high doses frequently is successful. Combination of penicillin and gentamicin probably is synergistic. Resistance increases with later generations of cephalosporins.

Like Leuconostoc species and other lactic-acid bacteria, pediococci are found on plants, in dairy products, and in alcohol-containing beverages. They also are used in the formation of silage and as starter cultures for some meat products. They are not thought to be part of normal human flora. Although formerly thought to be nonpathogenic, they now are considered rare opportunistic pathogens of minimal virulence.

Many cases of blood isolates are seen in patients without symptoms of infection or in polymicrobial cultures in which the significance of the isolate cannot be assessed adequately. Clear-cut cases of sepsis have occurred. Risk factors for bacteremia, with or without symptoms, appear to be extremes of age, recent abdominal surgery or tube feedings, broad-spectrum antimicrobial therapy, and the presence of severe underlying disease states.

Most patients are either asymptomatic or exhibit fever as the only symptom. Most reported cases of Pediococcus bacteremia have had concomitant pneumonia. Reported pediatric cases are in patients with underlying gastrointestinal tract anomalies. Isolation of Pediococcus as part of a polymicrobial process in localized infections is a common finding, especially from abdominal sites. Assessing the relative importance of Pediococcus in these sites is difficult. Bacteremic pneumonia in a previously healthy pregnant woman has been reported.

Diagnosis of infection with Pediococcus is made by identifying vancomycin-resistant, gram-positive cocci in its characteristic tetrads. Many pediococci initially are misidentified as Streptococcus equinus, Streptococcus constellatus, or group D streptococci, not enterococci, although they do not form chains. Hence, reported cases of pediococcal infection may represent only a fraction of the total number of infections. Generally, pediococci are susceptible to penicillin, ampicillin, imipenem, and first- and second-generation cephalosporins. Pediococci, like Leuconostoc, are intrinsically resistant to vancomycin. Generally, sensitivity to ticarcillin and cefotaxime is poor, despite large zones of inhibition by disc susceptibility testing. Aminoglycoside sensitivity is variable.

A. haemolyticum is recovered from 0.5% to 10.0% of children and adolescents presenting with pharyngitis. Selectivity for older children is unexplained. Organisms survive intracellularly, which may contribute to the difficulty encountered in eradicating penicillin-susceptible organisms.

A. haemolyticum causes a pharyngitis that resembles that seen in group A streptococcal infection except that palatal petechiae and strawberry tongue usually are absent. Circumoral pallor also is a rare finding. Approximately one-half of infections are associated with a maculopapular rash that typically is confined to extensor surfaces, sparing the trunk, palms, and soles. It often is scarlatiniform. Peritonsillar abscesses sometimes are seen. Infections other than pharyngotonsillitis are distinctly less common findings. However, reports of sinusitis and orbital cellulitis, including subperiosteal abscess requiring surgical debridement, have appeared. Soft-tissue abscesses and cellulitis are reported. Visceral infection or bacteremia is a rare occurrence; endocarditis in an intravenous drug abuser has been reported. Skin infection resembling ecthyma gangrenosum has been noted in tropical areas.

A. haemolyticum grows poorly on tellurite medium, which helps distinguish it from Corynebacterium diphtheriae. Tolerance for penicillin sometimes is noted, which may explain treatment failures with penicillin. Erythromycin is the treatment of choice for pharyngitis. Peritonsillar abscesses require prompt surgical therapy as well as appropriate antimicrobials.

B. anthracis can infect both domestic herbivores and many different types of wild animals. In the past, almost all cases of anthrax in the United States were cutaneous, caused by the contact of broken or abraded skin with spores or live bacilli. In late 2001, respiratory cases related to domestic terrorism
were reported. The current global environment continues to favor the possibility of bioterrorism events, and B. anthracis is a potential weapon. The extreme stability of anthrax spores allows this potential misuse. Considering the scarcity of naturally occurring inhalational anthrax, all cases should be presumed to be secondary to bioterrorism. B. anthracis contains three virulence factors: (a) edema toxin, (b) lethal toxin, and (c) a thick capsule. Edema toxin causes extravasation of fluid, leading to the edema characteristic of cutaneous disease. Lethal toxin increases proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin 1-beta (IL-1β). The capsule makes it difficult for the immune system to kill phagocytosed organisms.

B. cereus produces virulence factors, including a necrotizing enterotoxin, an emetic toxin, phospholipases, proteases, and hemolysins. B. cereus colonization of intravenous catheters may be aided by localization in adherent biofilms. Food-borne outbreaks of gastrointestinal illness are the most common manifestation of significant B. cereus infections; diarrhea caused by enterotoxin or vomiting from the emetic toxin are common complications after consumption of contaminated food. Improperly cooked fried rice may pose the greatest risk of B. cereus spore germination and toxin elaboration.

B. anthracis causes three distinct forms of disease: cutaneous, inhalational, and gastrointestinal.

Nonanthracis species of Bacillus can cause local and disseminated infection after traumatic injury, burns, or surgery. Local infection may be indolent, marked only by increased drainage at wound sites. B. cereus now is thought to be second only to Staphylococcus epidermidis as a cause of serious ophthalmic infection that develops after traumatic injury. A corneal ring abscess is the classic manifestation of eye infection. Findings include pain, chemosis, proptosis, and retinal hemorrhage. Eye infections are very aggressive, in part because of the elaboration of extracellular toxins and enzymes in the closed space of the globe.

B. cereus causes two food-poisoning syndromes, characterized by either diarrhea or vomiting. The diarrheal syndrome begins approximately 8 to 16 hours after consumption of contaminated food (usually meat) and resolves within 12 hours. The emetic toxin elaborated by growth of B. cereus in rice or pasta produces an illness similar to that of food poisoning caused by Staphylococcus aureus. After ingestion of toxin and a short incubation period of 1 to 5 hours, nausea, vomiting and, occasionally, diarrhea develop. Typically, affected individuals recover within 24 hours with minimal or supportive care.

A definitive diagnosis of cutaneous anthrax requires obtaining culture specimens prior to the institution of antibiotic therapy. Punch biopsy of the edge of the cutaneous lesion should be obtained for immunohistochemical testing and silver staining. Establishing the diagnosis of inhalational anthrax is difficult in the absence of an exposure history. Mediastinal widening is a helpful sign but may resemble that seen with mediastinal histoplasmosis. The diagnosis is established firmly if smears and cultures of pleural fluid and/or blood are positive for B. anthracis. Public health department reference laboratories have available specialized testing, such as polymerase chain reaction (PCR) or direct fluorescent antibody testing. Serologic testing has good sensitivity and specificity, but it is not positive until approximately 10 days into the disease.

Most B. anthracis isolates are sensitive to fluoroquinolones, rifampin, vancomycin, the carbapenems, tetracycline, the aminoglycosides, and clindamycin. They generally are resistant to cephalosporins and trimethoprim-sulfamethoxazole. Although most isolates are sensitive to penicillins, some contain penicillinases that may be inducible, which would render the organisms resistant to penicillin at some point during the course of treatment. Treatment recommendations largely are speculative and based largely on animal models of infection because of the paucity of human cases. Patients with bacteremia or other invasive disease generally are treated with more than one antibiotic; the combination of ciprofloxacin or tetracycline and an aminoglycoside or clindamycin often is used. Because tetracycline does not cross the blood brain barrier well, it should not be used for those patients with meningitis. In theory, clindamycin may be beneficial in decreasing the production of toxin, although this reduction has not been demonstrated specifically with regard to B. anthracis. Duration of therapy has not been established clearly; for cutaneous anthrax, 10 days usually is sufficient, but 60 days is the current standard for inhalational disease. Adjunctive measures such as chest tube drainage of pleural effusions and careful management of fluids and electrolytes are of paramount importance. Systemic steroids probably are beneficial for patients with massive edema and for patients with meningitis.

Bacillus species are common contaminants of blood cultures. Physicians must be alert to possible recovery of Bacillus as a pathogen. Bacillus species often are true pathogens in association with central venous lines in patients with neutropenia. Differentiating among individual species can be difficult. Usually, B. cereus can be distinguished from B. anthracis by phenotypic features of motility, beta-hemolysis, and penicillin resistance. Vancomycin and clindamycin are recommended for the treatment of serious Bacillus species infections; organisms commonly are resistant to penicillins and cephalosporins. Removal of the line is the most important aspect of treatment in neutropenic patients with line infections. Effective débridement
of local infection may be required for cure. Consultation with an ophthalmologist should be sought early for the management of eye infection.

Commonly, Corynebacterium species are recovered as normal flora in hospitalized patients. Nosocomial acquisition of C. jeikeium has been characterized most completely. Not surprisingly, patient-to-patient transmission in the hospital environment can occur, and selective antibiotic pressure augments colonization with Corynebacterium species. In some series, C. amycolatum is the most common isolate; in the past, many isolates were misidentified as C. striatum, C. ulcerans, or C. xerosis. Corynebacterium species, particularly C. jeikeium, possess lipophilic properties, which may account for their ability to proliferate on skin that has a higher lipid content. Infections have been described in neonates and immunocompromised older children. Intravascular access devices and breach of skin integrity are important risk factors for the development of local infection and bacteremia. Other risk factors include male gender, neutropenia, broad-spectrum antibiotic exposure, and prolonged hospital stay. Catalase production may be responsible for the rare infection with non-JK Corynebacterium species in children with chronic granulomatous disease.

Immunocompromised patients infected with C. jeikeium may demonstrate a local inflammatory lesion at the site of infection or may demonstrate a disseminated, hemorrhagic, or necrotic papular exanthem. C. jeikeium also is recognized to be one of the most common causes of prosthetic valve endocarditis in adults.

Although primarily a pathogen in sheep and goats, C. pseudotuberculosis can cause a localized granulomatous lymphadenitis in humans; almost all cases are associated with animal contact. C. amycolatum is a rare cause of endocarditis, catheter infections, and surgical wound infections. It has been reported as a cause of secondary septic arthritis and of fatal sepsis in a premature neonate. C. xerosis, C. pseudodiphtheriticum, and C. striatum are rare causes of pulmonary infection and endocarditis. C. ulcerans is a zoonotic pathogen that produces an ulcerative pharyngitis after contact with an infected animal or consumption of contaminated raw milk. Some strains of C. ulcerans produce diphtheria toxin and can cause serious illnesses that precisely mimic cutaneous or respiratory diphtheria. C. urealyticum (formerly Corynebacterium group D2) is a rare cause of alkaline-encrusted cystitis and sometimes pyelitis.

A diagnosis of Corynebacterium infection is based on isolation of the organism from clinical material. Vancomycin is recommended for empiric therapy of suspected Corynebacterium infection until susceptibilities are known. Almost all isolates also are susceptible to teicoplanin, which has been used successfully in some reported cases. Two-drug therapy that includes an aminoglycoside commonly is used for treatment of Corynebacterium endocarditis. Scrupulous attention to skin hygiene may reduce colonization of hospital personnel and the incidence of patient-to-patient transmission of pathogenic strains.

Erysipelothrix is a common commensal of wild and domestic animals and may be a saprophyte of soil. The organism is an important cause of epidemic disease in swine. Accordingly, those at risk for exposure to Erysipelothrix include fish handlers, meat processors, poultry workers, veterinarians, abattoir workers, and food handlers.

Usually, human infection results from contamination of skin abrasions exposed in handling colonized material. Males are infected more commonly than are females, perhaps because of increased exposure. The disease usually is self-limiting and most often involves the hands. Biopsy of the skin lesions reveals a marked inflammatory response. Childhood Erysipelothrix infection is unusual. Additional information about the clinical manifestations, diagnosis, and treatment of infections caused by Erysipelothrix is presented in Box 183.2.

Despite the common occurrence of this pathogen as a cause of veterinary infections, most reported human cases have not had farm or animal exposure. The organism lives in soil. Person-to-person transmission has not been documented. The appearance of pyogranulomatous lesions in the lung is consistent with the role of R. equi as a respiratory pathogen containing mycolic acid, a possible virulence factor in the cell wall. CD4⁺ lymphocytes may be essential for pulmonary clearance, which explains why persons infected with human immunodeficiency virus (HIV) comprise two-thirds of patients with proven R. equi infection. The appearance of an unusual appearing granulomatous inflammation, termed malakoplakia, in lung biopsy should raise suspicion of the presence of R. equi infection.

Symptoms of a slowly progressive pneumonia are common occurrences. Although most infections occur in patients with the acquired immunodeficiency syndrome (AIDS), malignancy and transplantation also pose risks. Often, pulmonary infection is pleura-based and associated with cavitation. Extrapulmonary
disease occurs in 7% of patients with R. equi pneumonia. Pericarditis and brain abscess have been reported.

Although sputum specimens may be positive for the organism, bronchoalveolar lavage or lung biopsy may be required. R. equi may coexist with other pathogens. Positive findings on Gram stain and Kinyoun stain should be interpreted in the context of clinical information. Commonly, clinical isolates are resistant to penicillins and cephalosporins. Erythromycin, clindamycin, rifampin, aminoglycosides, vancomycin, fluoroquinolones, and imipenem are active against R. equi. Combination antibiotic therapy and surgical resection often are required for cure.

A. calcoaceticus is distributed widely as a water-dwelling saprophyte and commensal in animals and humans. In hospitals, Acinetobacter has been isolated from personnel and from environmental sources. Most cases of Acinetobacter infections occur in patients who require endotracheal intubation or intravenous access. Risk factors include recent surgery, antibiotic therapy, and immunosuppression. Patients with serious underlying illnesses can become colonized rapidly with Acinetobacter from a highly contaminated environment. Often, a seasonal incidence of infection is observed, with a peak occurring during the late summer. Outbreaks have been reported from neonatal intensive care units (ICUs). Strict infection control is critical in halting such outbreaks.

Acinetobacter infection shares several features with other forms of gram-negative infection. Bacteremic patients present with fever and hypotension; patients rarely are asymptomatic. The lung is the most common site of primary infection, but infection associated with intravenous catheters occurs frequently. Often, other microbes are isolated from blood cultures that yield Acinetobacter, a finding that is associated with a poor prognosis.

Diagnosis is based on isolation of Acinetobacter from clinical material. Because of its coccobacillary shape, this organism may appear similar to Haemophilus or Neisseria on Gram stain. Its inability to grow anaerobically in any medium readily differentiates Acinetobacter from enteric bacteria. Prompt initiation of appropriate antimicrobial therapy and management of local infection caused by Acinetobacter usually results in a good outcome. However, selection of an antimicrobial agent may be complicated by the emergence of multiply resistant strains that display high-level resistance to aminoglycosides. Combination antibiotic therapy and third-generation cephalosporins have shown some efficacy in some cases. The carbapenems (imipenem/cilastatin and meropenem) were thought to be safe choices, but carbapenem resistance is emerging, and clonal spread of resistant organisms within communities has been well described. In some case series of multidrug-resistant Acinetobacter infections, ampicillin/sulbactam has led to decreased mortality rates. Final antibiotic choice should be based on detailed evaluation of the organism’s susceptibility.

Like Pseudomonas species, Achromobacter live in aqueous environments. In some people, they also may be part of the normal flora of the gastrointestinal and respiratory tracts. These organisms establish a niche within the hospital environment and have been recovered from ventilators, humidifiers, “sterile” saline, intravenous fluids, and even disinfectant solutions. Infection can be life-threatening in neonates and in immunocompromised hosts.

Achromobacter species are weakly virulent bacteria. Medical care provides the conduit through which organisms are introduced into their host. Preterm or small-for-gestational-age term infants are at particular risk of acquiring disseminated Achromobacter infections. Vertical transmission is rare. An increased incidence of infection has been reported for patients with neoplasms and for those with immunodeficiency states. Patients with cystic fibrosis may acquire Achromobacter infection. Infection with Achromobacter species may develop after a penetrating trauma has occurred in an otherwise normal host.