Fever & Bacteremia/Trench Fever/Endocarditis

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The four Bartonella species that are pathogenic for humans are capable of causing sustained or relapsing bacteremia accompanied by only fever (Table 1).

All except B bacilliformis also cause endocarditis.

After B quintana enters the body through broken skin from the excreta of the infected human body louse (Pediculus humanus), there is an incubation period of between 5 and 20 days before the onset of trench fever.

Patients complain of fever, myalgias, malaise, headache, bone pain — particularly of the legs, and a transient macular rash. Usually the illness continues for 4-6 weeks. Sustained or recurrent bacteremia is common, with or without symptoms.

Trench fever

The form of trench fever described in the United States and Europe in the 1990s (urban trench fever) has no distinguishing features other than fever, malaise, and weight loss. Endocarditis has been reported in conjunction with B quintana bacteremia.

In HIV-infected patients, B henselae bacteremia usually presents insidiously with malaise, fatigue, weight loss, and fevers. Endocarditis may occur in immunocompetent hosts with patients presenting with fever and malaise.

Diagnosis

Difficulty in the identification and isolation of Bartonella species from blood and tissue has made a diagnosis of infection with these organisms a challenge. Direct examination of tissue (not blood) with special stains is required, and special conditions for cultivation from tissue and blood are necessary.

The detection of these small, curved gram-negative bacilli in pathology specimens is best made by using the Warthin-Starry silver stain, electron microscopy, immunofluorescence, or the polymerase chain reaction.

Conventional stains such as acid-fast, Giemsa, periodic acid-Schiff, and the Brown-Brenn modification of Gram's stain fail to demonstrate the bacilli. The Warthin-Starry stain results are not pathognomonic since it also stains other bacteria, including spirochetes and species of Nocardia, Legionella, and Campylobacter. Polymerase chain reaction-based assays offer high sensitivity and specificity but are not widely available.

Isolation of B henselae and B quintana after homogenization of tissue such as liver, spleen, lymph node, and skin can be performed by direct plating or by cocultivation with an endothelial cell line. The cocultivation method, while useful in recovering organisms, may not be practical for most microbiology laboratories. Growth of strains on freshly prepared heart infusion agar containing 5% or 10% defibrinated rabbit or horse blood has been more successful than growth on other cell-free media such as chocolate or 5% sheep blood agar.

The lysis-centrifugation blood culture system is currently the best method to isolate Bartonella species from the blood. If bacteremia with a Bartonella species is suspected, the laboratory must be informed in order that lysis centrifugation-processed blood can be placed on the appropriate media and incubated for at least 7-14 days. Because of the fastidious nature of these organisms, the interval from collection to processing should be minimized. Other alternatives to the lysis centrifugation method include screening suspected blood culture bottle contents with an acridine orange staining procedure and subculturing positive bottles.

Differentiation of the Bartonella species can be accomplished with biochemical and molecular methods. Cellular fatty acid analysis by gas liquid chromatography can be helpful, but many laboratories do not have the necessary capabilities to perform this test. The Microscan rapid anaerobic panel has been used with some success to distinguish between B henselae and B quintana. Other methods have included polymerase chain reaction-restriction fragment length polymorphism analysis of the citrate synthase gene and 16S rDNA sequence analysis.

Serologic testing is easier and more rapid than cultivation of the organism and has become the mainstay for confirming the diagnosis of cat scratch disease. Both immunofluorescence assays and enzyme immunoassays are available to detect cerebrospinal fluid and serum immunoglobulin G (IgG) and IgM directed against Bartonella spp. A titer of > 1:64 or a fourfold rise in titer is considered positive. Because of the cross-reactivity of antibodies against B quintana and B henselae, definitive species identification is difficult with these methods.

Treatment

Treatment of Bartonella-associated disease varies according to the clinical syndrome (Box 2). All recommendations are based on anecdotal evidence of treatment response since controlled trials have not been performed.

Bacillary angiomatosis should always be treated. Spontaneous resolution of superficial skin papules has been reported, but relapse and bacterial dissemination are common. Nevertheless, therapeutic endpoints remain undefined.

Anecdotal evidence strongly favors the use of oral erythromycin for treatment of bacillary angiomatosis at a dose of 500 mg four times per day for 8-12 weeks. Intravenous erythromycin should be administered to patients with severe disease or patients who are unable to take oral medications. Longer courses may be necessary in patients with bacteremia/endocarditis or bacillary peliosis and those with disease recurrence. The newer macrolides, azithromycin and clarithromycin, may also be effective, but experience with these drugs is more limited. Oral doxycycline (100 mg twice daily) has been consistently successful in the treatment of bacillary angiomatosis. Jarisch-Herxheimer-like reactions after the first several doses of doxycycline or erythromycin can occur, however. Use of an antipyretic before treatment may attenuate this response.

Limited data support the use of ciprofloxacin in the treatment of bacillary angiomatosis. Inhibitors of cell wall synthesis, such as the penicillins and cephalosporins, uniformly fail to cure the disease, despite the fact that in vitro testing indicates that both B quintana and B henselae are sensitive to these antibiotics. Susceptibility testing is not standardized for B henselae or B quintana and is difficult to perform. In vitro data should not be used to guide therapy at this time.

Cat scratch disease usually resolves spontaneously over a 2- to 8-week period. Aspiration of a suppurative node may provide symptomatic relief. Antibiotic therapy is not consistently successful, nor is it routinely indicated, unless the disease occurs in an immunocompromised host. Despite the success of macrolides and tetracyclines in the treatment of bacillary angiomatosis, they have not been used as widely in the treatment of cat scratch disease. A prospective, randomized, double-blind trial has suggested that azithromycin treatment for 5 days reduces lymph node size more rapidly than placebo. Rifampin, ciprofloxacin, trimethoprim-sulfamethoxazole, and gentamicin have been proposed as effective agents, based only on a retrospective review of the literature. Mild or moderate disease should receive only symptomatic therapy, since antimicrobial agents do not change the clinical outcome of cat scratch disease in the majority of cases.

Urban trench fever has been suppressed and sometimes cured with erythromycin or azithromycin given for at least 4 weeks; however, as with B henselae bacteremia, response to antimicrobial agents is variable, and some patients experience a relapse of symptoms after cessation of antibiotics. Some cases of endocarditis require valve replacement and most require prolonged antibiotic therapy.

The response of Oroya fever and verruga peruana to therapy is variable. Chloramphenicol has been recommended in endemic regions due to the possibility of intercurrent Salmonella infection and the high case fatality rate.

Prevention & Control

Cat owners can, and immunocompromised individuals should, reduce their risk of cat scratch disease or bacillary angiomatosis (Box 3). Cat owners who are immunocompromised should (1) wash hands after animal contact and keep all wounds and abrasions as clean as possible; (2) avoid cats < 1 year of age or avoid rough play with them since they are more prone to "carry" the organism; and (3) keep cats as free from fleas as possible. Declawing of cats is not recommended. Antibiotic treatment of infected cats is not useful.

B quintana infection may be prevented or controlled by delousing procedures. These include regular changing or washing of clothes and bedding. Insecticides such as permethrin should also be used to control louse infestation. Oroya fever and verruga peruana can be prevented by avoiding the bite of the sandfly vector. These insects tend to be nocturnal feeders.

Links

http://emedicine.medscape.com/article/961169-overview

http://www.patientcareonline.com/articles/fever-bacteremia-children

http://www.msdmanuals.com/professional/pediatrics/miscellaneous-bacterial-infections-in-infants-and-children/occult-bacteremia-and-fever-without-apparent-source-in-infants-and-young-children

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