Brevibacterium casei Sepsis in an 18-Year-Old Female with AIDS

Abstract

Brevibacterium sp. was isolated from the blood of an acutely ill 18-year-old female with AIDS. The isolate was identified as Brevibacterium casei by use of carbohydrate assimilation tests. Treatment was successful with intravenously administered ciprofloxacin. To our knowledge, this is the first report of sepsis caused by B. casei in a human immunodeficiency virus-infected patient.

CASE REPORT

An 18-year-old female from Ruanda, adopted by Swiss foster parents at 5 years of age, was diagnosed as being infected with human immunodeficiency virus type 1 (HIV-1) in 1991. She suffered a complicated course during subsequent years with oral hairy leukoplakia in 1992, neutropenia and anemia in 1993, herpes zoster in 1995, and severe wasting due to untreatable recurrent episodes of vomiting and diarrhea thereafter. A Port-a-cath system (Pharmacia Upjohn Hospital Group, Dübendorf, Switzerland) was implanted in 1997 for partial parenteral nutrition. Unfortunately, the Port-a-cath had to be exchanged twice due to catheter infection caused by coagulase-negative staphylococci (CoNS) and thrombosis in July and October 1997.

In April 1999, the patient presented to a primary-care hospital with high fever that had persisted for 10 days and marked dehydration. CoNS were isolated from blood culture. Fever persisted despite antibiotic treatment with amoxicillin-clavulanate (1.2 g three times a day), and the patient was transferred to our center. One set of peripheral cultures as well as blood cultures (Bactec; Becton Dickinson Microbiology Systems, Cockeysville, Md.) from the Port-a-cath taken by us on admission grew gram-positive rods after 48 h. Overnight subcultures on Columbia blood agar (Becton Dickinson) revealed whitish colonies, which were identified as Brevibacterium sp. by use of the commercially available API Coryne system (version 2.0; bioMérieux, Marcy-l'Etoile, France), which has a 94.2% probability of identification and a T index of 0.94 (code 4112004). Tests for pyrrolidonyl arylamidase, alcaline phosphatase, alpha glucosidase, hydrolysis of gelatine, and catalase were positive, but acid was not produced from glucose and other carbohydrates. The Port-a-cath was removed, and antibiotic treatment was changed to intravenously administered ciprofloxacin (400 mg twice a day). Our patient's clinical condition improved rapidly, and fever resolved within 2 days. After treatment for 14 days, a new Port-a-cath was implanted and the patient was dismissed shortly thereafter.

Microbiology.

Patients with indwelling central venous catheters are at high risk of acquiring bloodstream infections. Among a wide range of causative agents, Brevibacterium spp. are rarely found (1). Here we report isolation of Brevibacterium casei from a Port-a-cath system and from peripheral blood in an acutely ill patient with AIDS and wasting syndrome.

The patient's isolate was sent to the Department of Medical Microbiology in Zurich, Switzerland, for further identification. The gram-positive short coryneform rods formed whitish gray colonies with a distinctive cheese-like smell typical of Brevibacterium spp., and their identity was confirmed by conventional tests, i.e., production of methanethiol and hydrolysis of casein and tyrosine (2). The isolate was identified as B. casei by use of carbohydrate assimilation tests previously described (3). Briefly, 3 × 10⁸ bacterial cells in 1 ml of 0.85% NaCl were transferred to 15 ml of AUX medium (bioMérieux), and 300 μl of this suspension was transferred into each cupule of the API 50CH system (bioMérieux) and incubated at 37°C for 48 h before assimilation tests were read. Opaque cupules indicated a positive reaction, i.e., bacterial growth. Cupules without bacterial growth remained clear (negative reaction). Based on the assimilation of d-arabinose, N-acetylglucosamine, maltose, saccharose, trehalose, d-turanose, and l-fucose and lack of growth with mannitol and d-arabitol, a clear distinction from other Brevibacterium spp. could be made (3). Furthermore, the analysis of cellular fatty acids revealed 9.5% i-C_15:0, 47.5% a-C_15:0, 5% i-C_16:0, 0.5% C_16:0, 2.4% i-C_17:0, and 33.5% a-C_17:0; this composition is in line with those published by Funke and Carlotti (3).

MICs were determined by the E-test (AB Biodisk, Solna, Sweden) procedure on Mueller-Hinton agar (Becton Dickinson). The plates were swabbed with an inoculum in 0.85% NaCl with a turbidity equal to a 0.5 McFarland standard. Plates were incubated at 35°C for 24 h at ambient air temperature. The MICs of amoxicillin-clavulanic acid, ampicillin, ciprofloxacin, clindamycin, erythromycin, gentamicin, penicillin, teicoplanin, tetracycline, and vancomycin were 1.5 mg/ml, 2 mg/liter, 0.75 mg/liter, 1.5 mg/liter, 0.5 mg/liter, 0.75 mg/liter, 1 mg/liter, 0.25 mg/liter, 0.5 mg/liter, and 0.38 mg/liter, respectively. Interpretative breakpoints are not available for coryneform bacteria, but our results of decreased susceptibilities to beta-lactams are in line with the data of Funke et al. (4). We assume from the clinical improvement of our patient that the isolate was susceptible to ciprofloxacin, which has a MIC of 0.75 mg/liter.

Brevibacteria are catalase-positive, non-spore-forming, nonmotile, aerobic gram-positive rods. They can be found in raw milk and surface-ripened cheese as well as on human skin and in animal sources. The genus Brevibacterium currently consists of six species, namely, B. linens, B. casei, B. epidermidis, B. iodinum, B. mcbrellneri, and B. otitidis (5). Despite earlier reports of Brevibacterium spp. isolated from humans (7, 9, 10), they had been considered a nonpathogenic species. In 1994, Gruner and collaborators found that of 41 strains in the collection of the Bacteriology Reference Laboratory of the Centers for Disease Control and Prevention, which were formerly assigned to CDC groups B-1 and B-3, 22 were in fact B. casei and most of them were isolated from blood cultures (6). Other reports followed, and it is now accepted that B. casei is by far the most frequently isolated Brevibacterium from otherwise sterile human sites (1, 3, 6, 11). Although B. casei can cause a variety of infections, such as sepsis, meningitis, cholangitis, salpingitis, and peritonitis, most isolates derive from blood cultures, as exemplified by 19 of 42 isolates collected by Funke and Carlotti from various laboratories in Europe and Ottawa, Canada (3).

Patients with indwelling central venous catheters are at high risk of acquiring bloodstream infections. Among a wide range of causative agents, CoNS, Staphylococcus aureus, gram-negative rods, and Candida species are most frequently isolated (8). However, a variety of unusual pathogens may also be encountered, especially in immunocompromised patients. Among these, Brevibacterium spp. are rarely found (1, 11). The observation of B. casei sepsis in an AIDS patient is new and adds this species to the list of unusual pathogens complicating HIV infection. Since brevibacteria may easily be confused with apathogenic corynebacteria, physicians treating patients with HIV infection and other immunocompromising conditions should be aware of this bacterial genus as a potential cause of invasive infection.