Chryseobacterium (Flavobacterium) meningosepticum- A Beta-Lactam Buster
ABSTRACT & COMMENTARY
Synopsis: Chryseobacterium (Flavobacterium) meningosepticum, an organism resistant to multiple antibiotics, is an occassional cause of infection in immunocompromised adults and in neonates, in whom it most commonly causes meningitis.
Source: Di Pentima MC, et al. In vitro antibiotic synergy against Flavobacterium meningosepticum: Implications for therapeutic options. Clin Infect Dis 1998;26:1169-1176.
Di pentima and colleagues in houston, texas, reviewed their experience with four cases of neonatal infection due to bacteremic Chryseobacterium (Flavobacterium) meningosepticum that were seen between 1982 and 1996. Three newborns, all full-term, presented with F. meningosepticum meningitis at 23-59 days of life. All three were treated with regimens that included vancomycin and rifampin. Each survived without hydrocephalus, although two were left with mild sensorinueural hearing loss. The fourth child was born at 27 weeks weighing 850 g; he developed bacteremia three weeks later that responded to treatment with ceftazidime and vancomycin.
MICs were determined using broth macrodiluton. The most potent agents tested were ciprofloxacin (MIC range: 0.125 mcg/mL-0.5 mcg/mL) and rifampin (MIC range: 0.25 mcg/mL-1.56 mcg/mL); their MBCs were generally within one dilution of their MICs. Vancomycin was not particularly active, with MICs of 16-64 mcg/mL. However, vancomycin and rifampin were synergistic (as determined by fractional inhibitory concentrations) against three of the four isolates. Meropenem (MIC: 16 mcg/mL) and ciprofloxacin were each additive with rifampin in their activity. The MICs of the oxazolidinone, linezolid, were 2-4 mcg/mL, and this drug was additive when combined with ciprofloxacin or vancomycin and additive or indifferent with rifampin.
COMMENT BY STAN DERESINSKI, MD, FACP
F. meningosepticum, recently reclassified as Chryseobacterium meningosepticum, is present in a variety of ecological niches, including soil, water, plants, and food. It is a pathogen for birds, including chickens, pigeons, and finches, as well as leopard frogs, and is found as an intracellular endosymbiont of the cockroach fat body.1-3 The organism is a nonmotile, catalase- and oxidase-positive, non-fermenting or slowly fermenting Gram-negative bacillus with resistance to multiple antibiotics.
The organism most commonly causes neonatal meningitis (approximately two-thirds of reported infections occur in infants less than 3 months of age) but also causes a variety of infections in immunocompromised adults. Infections with this organism, however, remain uncommon, as indicated by the Houston experience and those of others. Bloch and colleagues recently found only six such infections in immunocompromised adults at their institution during a 10-year period.4
Resistance to many beta-lactam antibiotics is the rule for this organism and is the consequence of the presence of a chromosomally mediated non-inducible metallo-b-lactamase able to hydrolyze penicillins, cephamycins, cephalosporins, monobactams, and carbapenems.5 The gene encoding this enzyme has significant sequence homology with those of the metallo-enzymes of Bacteroides fragilis and the IMP-1 enzyme; it is more distantly related to the metallo-enzymes of Aeromonas spp. and Stenotrophomonas maltophilia.6
As a consequence, C. meningosepticum is resistant to most b-lactam antibiotics, including imipenem and cefepime.7-9 Many strains, however, remain susceptible to piperacillin, for which the MIC90 of 41 strains isolated in Taiwan was reported to be 8 mcg/mL.7 Other antibiotics with reasonable activity include rifampin, the fluoroquinolones, minocycline, and, perhaps, the oxazidinolones. Trimethoprim-sulfamethoxazole may also have some activity. The MIC90 of vancomycin was reported to be 16 mcg/mL.7
These data suggest that the optimal initial choice of therapy for treatment of infections due to this organism, prior to receipt of specific antimicrobial susceptibility data, may be piperacillin, a fluoroquinolone, or minocycline. In infants with meningitis, however, none of these are optimal choices. The MIC90 of 8 mcg/mL of piperacillin is a concentration higher than can ordinarily be achieved in the cerebrospinal fluid, while the other two drugs are considered contraindicated in this age group (although the seriousness of the infection makes this caveat only a relative one). The experience reported by Di Pentima et al with the use of vancomycin and rifampin in combination is, however, encouraging and raises the possibility that adding rifampin to an antibiotic with greater activity than vancomycin against this organism may be even more efficacious.
References
1. Vancanneyt M, et al. J Clin Microbiol 1994;32: 2398-2403.
2. Taylor FR, et al. Lab Anim Sci 1993;43:105.
3. Bandi C, et al. Proc R Soc Lond B Biol Sci 1994;257: 43-48.
4. Bloch KC, et al. Medicine (Baltimore) 1997;76:30-41.
5. Blahovß J, et al. Eur J Clin Microbiol Infect Dis 1994; 13:833.
6. Rossolini GM, et al. Biochem J 1998;332(Pt1):145-152.
7. Chang JC, et al. Antimicrob Agents Chemother 1997; 41:1301-1306.
8. Fraser SL, Jorgensen JH. Antimicrob Agents Chemother 1997;41:2738-2741.
9. Hsueh PR, et al. J Clin Microbiol 1997;35:3323-3324.
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