J Korean Med Sci.  2004 Feb;19(1):21-26. 10.3346/jkms.2004.19.1.21.

Therapeutic Efficacy of Meropenem for Treatment of Experimental Penicillin-Resistant Pneumococcal Meningitis

• Kim SW
• Jin JH
• Kang SJ
• Jung SI
• Kim YS
• Kim CK
• Lee H
• Oh WS
• Kim S
• Peck KR
• Song JH

• KMID: 1785688
• DOI: http://doi.org/10.3346/jkms.2004.19.1.21

Abstract

With the widespread emergence of antimicrobial resistance, combination regimens of ceftriaxone and vancomycin (C+V) or ceftriaxone and rifampin (C+R) are recommended for empirical treatment of pneumococcal meningitis. To evaluate the therapeutic efficacy of meropenem (M), we compared various treatment regimens in arabbit model of meningitis caused by penicillin-resistant Streptococcus pneumoniae (PRSP). Therapeutic efficacy was also evaluated by the final bacterial concentration in the cerebrospinal fluid (CSF) at 24 hr. Each group consisted of six rabbits. C+V cleared the CSF at 10 hr, but regrowth was noted in 3 rabbits at 24 hr. Meropenem monotherapy resulted in sterilization at 10 hr, but regrowth was observed in all 6 rabbits at 24 hr. M+V also resulted in sterilization at 10 hr, but regrowth was observed in 2 rabbits at 24 hr. M+V was superior to the meropenem monotherapy at 24 hr (reduction of 4.8 vs. 1.8 log10 cfu/mL, respectively; p=0.003). The therapeutic efficacy of M+V was comparable to that of C+V (reduction of 4.8 vs. 4.0 log10 cfu/mL, respectively; p=0.054). The meropenem monotherapy may not be a suitable choice for PRSP meningitis, while combination of meropenem and vancomycin could be a possible alternative in the treatment of PRSP meningitis.

Keyword

Meningitis; Pneumococcal; Carbapenems; Penicillin Resistance; Cephalosporin Resistance

MeSH Terms

Animals
Anti-Bacterial Agents/pharmacology
Cerebrospinal Fluid
Disease Models, Animal
*Drug Resistance, Microbial
Human
Male
Meningitis, Pneumococcal/*drug therapy
Penicillins/*pharmacology
Rabbits
Streptococcus pneumoniae
Support, Non-U.S. Gov't
Thienamycins/*pharmacology
Time Factors

Figure

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  Fig. 1 Therapeutic efficacies of ceftriaxone and meropenem by mean bacterial concentrations in the CSF. The difference in ΔLog10 cfu/mL in CSF at 24 hr was not statistically significant.

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  Fig. 2 Therapeutic efficacies of meropenem, vancomycin, and M+V by mean bacterial concentrations in the CSF. The difference in ΔLog10 cfu/mL in CSF at 24 hr between M+V and meropenem was significant (p=0.003), but M+V and vancomycin was not significant (p=0.181) by Tukey's HSD test.

• 

  Fig. 3 Therapeutic efficacies of C+V and M+V by mean bacterial concentrations in the CSF. The difference in ΔLog10 cfu/mL in CSF at 24 hr was not significant (p=0.054).

• 

  Fig. 4 Therapeutic efficacies of C+V, M+V, and C+R by mean bacterial concentrations in the CSF. The difference in ΔLog10 cfu/mL in CSF at 24 hr was not significant.

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