CHAPTER 55: INFECTIONS DUE TO THE HACEK GROUP AND MISCELLANEOUs GRAM-NEGATIVE BACTERIA

HACEK organisms are a group of fastidious, slow-growing, gram-negative bacteria whose growth requires an atmosphere of carbon dioxide. Species belonging to this group include several Haemophilus species, Aggregatibacter (formerly Actinobacillus) species, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae. HACEK bacteria normally reside in the oral cavity and have been associated with local infections in the mouth. They are also known to cause severe systemic infections—most often bacterial endocarditis, which can develop on either native or prosthetic valves (Chap. 20).

In large series, 0.8–6% of cases of infective endocarditis are attributable to HACEK organisms, most often Aggregatibacter species, Haemophilus species, and C. hominis. Invasive infection typically occurs in patients with a history of cardiac valvular disease, often in the setting of a recent dental procedure or nasopharyngeal infection. The aortic and mitral valves are most commonly affected. Compared with non-HACEK endocarditis, HACEK endocarditis occurs in younger patients and is more frequently associated with embolic, vascular, and immunologic manifestations but less commonly associated with congestive heart failure. The clinical course of HACEK endocarditis tends to be subacute, particularly with Aggregatibacter or Cardiobacterium. However, K. kingae endocarditis may have a more aggressive presentation. Systemic embolization is common. The overall prevalence of major emboli associated with HACEK endocarditis ranges from 28% to 71% in different series. On echocardiography, valvular vegetations are seen in up to 85% of patients. Aggregatibacter and Haemophilus species cause mitral valve vegetations most often; Cardiobacterium is associated with aortic valve vegetations. The microbiology laboratory should be alerted when a HACEK organism is being considered; however, most cultures that ultimately yield a HACEK organism become positive within the first week, especially with improved culture systems such as BACTEC. In addition, polymerase chain reaction (PCR) techniques (e.g., of cardiac valves) and other tools, such as matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry performed directly on agar colonies, are facilitating the diagnosis of HACEK infections. Because of the organisms’ slow growth, antimicrobial testing may be difficult, and β-lactamase production may not be detected. Resistance is most commonly noted in Haemophilus and Aggregatibacter species. E-test methodology may increase the accuracy of susceptibility testing. The overall prognosis in HACEK endocarditis is excellent and significantly better than that in endocarditis caused by non-HACEK pathogens.

Haemophilus species

Haemophilus parainfluenzae is the most common species isolated from cases of HACEK endocarditis. Of patients with HACEK endocarditis due to Haemophilus species, 60% have been ill for <2 months before presentation, and 19–50% develop congestive heart failure. Mortality rates as high as 30–50% were reported in older series; however, more recent studies have documented mortality rates of <5%. H. parainfluenzae has been isolated from other infections, such as meningitis; brain, dental, pelvic, and liver abscess; pneumonia; urinary tract infection; and septicemia.

Aggregatibacter species

The species of Aggregatibacter that most frequently cause infective endocarditis are A. actinomycetemcomitans, A. (formerly Haemophilus) aphrophilus, and A. paraphrophilus. Aggregatibacter is associated with prosthetic valve endocarditis more often than are Haemophilus species. A. actinomycetemcomitans can be isolated from soft tissue infections and abscesses in association with Actinomyces israelii. Typically, patients who develop endocarditis with Aggregatibacter have periodontal disease or have recently undergone dental procedures in the setting of underlying cardiac valvular damage. The disease is insidious; patients may be sick for several months before diagnosis. Frequent complications include embolic phenomena, congestive heart failure, and renal failure. A. actinomycetemcomitans has been isolated from patients with brain abscess, meningitis, endoph-thalmitis, parotitis, osteomyelitis, urinary tract infection, pneumonia, and empyema, among other infections, while A. aphrophilus is often associated with bone and joint infection.

Cardiobacterium hominis

C. hominis primarily causes endocarditis in patients with underlying valvular heart disease or with prosthetic valves. This organism most frequently affects the aortic valve. Many patients have signs and symptoms of long-standing infection before diagnosis, with evidence of arterial embolization, vasculitis, cerebrovascular accidents, immune complex glomerulonephritis, or arthritis at presentation. Embolization, mycotic aneurysms, and congestive heart failure are common complications. A second species, C. valvarum, has now been described in association with endocarditis.

Eikenella corrodens

E. corrodens is most frequently recovered from sites of infection in conjunction with other bacterial species. Clinical sources of E. corrodens include sites of human bite wounds (clenched-fist injuries), endocarditis, soft tissue infections, osteomyelitis, head and neck infections, respiratory infections, chorioamnionitis, gynecologic infections associated with intrauterine devices, meningitis, brain abscesses, and visceral abscesses. This organism is the least common cause of HACEK endocarditis.

Kingella kingae

Because of improved microbiologic methodology and molecular methods such as real-time PCR, the isolation of K. kingae is increasingly common. Inoculation of clinical specimens (e.g., synovial fluid) into aerobic blood culture bottles enhances recovery of this organism. More than half of cases of K. kingae infection are bone and joint infections; the majority of the remaining infections are infective endocarditis and bacteremia. PCR studies of joint fluid can identify K. kingae in culture-negative cases. Some studies now demonstrate that K. kingae has surpassed Staphylococcus aureus as the leading cause of septic arthritis in children. Invasive K. kingae infections with bacteremia are associated with upper respiratory tract infections and stomatitis in 80% of cases. Rates of oropharyngeal colonization with K. kingae are highest in the first 3 years of life (detected in ~10% of children), coinciding with an increased incidence of skeletal infections due to this organism. K. kingae bacteremia can present with a petechial rash similar to that seen in Neisseria meningitidis sepsis.

Infective endocarditis, unlike other infections with K. kingae, occurs in older children and adults. The majority of patients have preexisting valvular disease. There is a high incidence of complications, including arterial emboli, cerebrovascular accidents, tricuspid insufficiency, and congestive heart failure with cardiovascular collapse.

TREATMENT

Achromobacter xylosoxidans

Achromobacter (previously Alcaligenes) xylosoxidans is probably part of the endogenous intestinal flora and has been isolated from a variety of water sources, including well water, IV fluids, and humidifiers. Immunocompromised hosts, including patients with cancer and postchemotherapy neutropenia, cirrhosis, chronic renal failure, and cystic fibrosis, are at increased risk. Nosocomial outbreaks and pseudo-outbreaks of A. xylosoxidans infection have been attributed to contaminated fluids, and clinical illness has been associated with isolates from many sites, including blood (often in the setting of intravascular devices). Community-acquired A. xylosoxidans bacteremia usually occurs in the setting of pneumonia. Metastatic skin lesions are present in one-fifth of cases. The reported mortality rate is as high as 67%—a figure similar to rates for other bacteremic gram-negative pneumonias.

TREATMENT

Aeromonas species

More than 85% of Aeromonas infections are caused by A. hydrophila, A. caviae, and A. veronii biovar sobria. Aeromonas proliferates in potable water, freshwater, and soil. It remains controversial whether Aeromonas is a cause of bacterial gastroenteritis; asymptomatic colonization of the intestinal tract with Aeromonas occurs frequently. However, rare cases of hemolytic-uremic syndrome following bloody diarrhea have been shown to be secondary to the presence of Aeromonas.

Aeromonas causes sepsis and bacteremia in infants with multiple medical problems and in immunocompromised hosts, particularly those with cancer or hepatobiliary disease. A. caviae is associated with health care–related bacteremia. Aeromonas infection and sepsis can occur in patients with trauma (including severe trauma with myonecrosis) and in burn patients exposed to Aeromonas by environmental (freshwater or soil) contamination of their wounds. Reported mortality rates range from 25% among immunocompromised adults with sepsis to >90% among patients with myonecrosis. Aeromonas can produce ecthyma gangrenosum (hemorrhagic vesicles surrounded by a rim of erythema with central necrosis and ulceration; see Fig. 14-35) resembling the lesions seen in Pseudomonas aeruginosa infection. This organism causes nosocomial infections related to catheters, surgical incisions, or use of leeches. Other manifestations include necrotizing fasciitis, meningitis, peritonitis, pneumonia, and ocular infections.

TREATMENT

Capnocytophaga species

This genus of fastidious, fusiform, gram-negative coccobacilli is facultatively anaerobic and requires an atmosphere enriched in carbon dioxide for optimal growth. C. ochracea, C. gingivalis, C. haemolytica, and C. sputigena have been associated with sepsis in immunocompromised hosts, particularly neutropenic patients with oral ulcerations. These species have been isolated from many other sites as well, usually as part of a polymicrobial infection. Most Capnocytophaga infections are contiguous with the oropharynx (e.g., periodontal disease, respiratory tract infections, cervical abscesses, and endophthalmitis).

C. canimorsus and C. cynodegmi are endogenous to the canine mouth (Chap. 40). Patients infected with these species frequently have a history of dog bites or of canine exposure without scratches or bites. Asplenia, glucocorticoid therapy, and alcohol abuse are predisposing conditions that can be associated with severe sepsis with shock and disseminated intravascular coagulation. Patients typically have a petechial rash that can progress from purpuric lesions to gangrene. Meningitis, endocarditis, cellulitis, osteomyelitis, and septic arthritis also have been associated with these organisms.

TREATMENT

Elizabethkingia/Chryseobacterium species

Elizabethkingia meningoseptica (formerly Chryseobacterium meningosepticum) is an important cause of nosocomial infections, including outbreaks due to contaminated fluids (e.g., disinfectants and aerosolized antibiotics) and sporadic infections due to indwelling devices, feeding tubes, and other fluid-associated apparatuses. Nosocomial E. meningoseptica infection usually involves neonates or patients with underlying immunosuppression (e.g., related to malignancy or diabetes). E. meningoseptica has been reported to cause meningitis (primarily in neonates), pneumonia, sepsis, endocarditis, bacteremia, and soft tissue infections. Most published reports have originated from Taiwan. Chryseobacterium indologenes has caused bacteremia, sepsis, and pneumonia, typically in immunocompromised patients with indwelling devices.

TREATMENT

Pasteurella multocida

P. multocida is a bipolar-staining, gram-negative coccobacillus that colonizes the respiratory and gastrointestinal tracts of domestic animals; oropharyngeal colonization rates are 70–90% in cats and 50–65% in dogs. P. multocida can be transmitted to humans through bites or scratches, via the respiratory tract from contact with contaminated dust or infectious droplets, or via deposition of the organism on injured skin or mucosal surfaces during licking. Most human infections affect skin and soft tissue; almost two-thirds of these infections are caused by cats. Patients at the extremes of age or with serious underlying disorders (e.g., cirrhosis, diabetes) are at increased risk for systemic manifestations, including meningitis, peritonitis, osteomyelitis and septic arthritis, endocarditis, and septic shock, but cases have also occurred in healthy individuals of all ages. If inhaled, P. multocida can cause acute respiratory tract infection, particularly in patients with underlying sinus and pulmonary disease.

TREATMENT

Rhizobium (formerly Agrobacterium) radiobacter has usually been associated with infection in the presence of medical devices, including intravascular catheter–related infections, prosthetic-joint and prosthetic-valve infections, and peritonitis caused by dialysis catheters. Cases of endophthalmitis after cataract surgery also have been described. Most R. radiobacter infections occur in immunocompromised hosts, especially individuals with malignancy or HIV infection. Strains are usually susceptible to fluoroquinolones, third- and fourth-generation cephalosporins, and carbapenems (Table 55-2).

Shewanella putrefaciens and S. algae are ubiquitous organisms found primarily in seawater. Devitalized tissues can become colonized with Shewanella and serve as a nidus for systemic infection. Shewanella species cause skin and soft tissue infections, chronic ulcers of the lower extremities, ear infections, biliary tract infections, pneumonia, necrotizing fasciitis, bacteremia, and sepsis. A fulminant course is associated with cirrhosis, diabetes mellitus, malignancy, or other severe underlying conditions. Organisms are often susceptible to fluoroquinolones, third- and fourth-generation cephalosporins, β-lactam/β-lactamase inhibitors, carbapenems, and aminoglycosides (Table 55-2).

Chromobacterium violaceum has been responsible for life-threatening infections with severe sepsis and metastatic abscesses, particularly in children with defective neutrophil function (e.g., those with chronic granulomatous disease). Ochrobactrum anthropi causes infections related to central venous catheters in compromised hosts; other invasive infections have been described. Other organisms implicated in human infections include Weeksella species; various CDC groups, such as Ve-1 and Ve-2; Flavimonas species; Sphingobacterium species; and Oligella urethralis. The reader is advised to consult subspecialty texts and references for further guidance on these organisms.