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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 - J. Korean Med. Sci. (2004)

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Disiases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, Korea.

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 a rabbit 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.

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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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Figure 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.

Mentions: CSF bacterial concentrations in each rabbit treatment group are shown in Fig. 1, 2, 3, and 4. Meropenem resulted in sterilization at 10 hr but regrowth was observed in all 6 rabbits at 24 hr (Table 3, Fig. 1). Meropenem plus vancomycin resulted in sterilization in all 6 rabbits at 10 hr, and regrowth was observed in 2 rabbits at 24 hr (Table 3 and Fig. 2). Meropenem therapy resulted in 5 log10 cfu/mL reduction in the bacterial concentration within 10 hr, but regrowth was observed at 24 hr (Table 4 and Fig. 1). Meropenem plus vancomycin resulted in 4.8 log10 cfu/mL reduction in the bacterial concentration within 10 hr. The effect persisted until 24 hr (Table 4 and Fig. 2), but regrowth was observed in 2 rabbits (Fig. 2). Compared with meropenem and ceftriaxone, ceftriaxone showed a less reduction of bacteria at 10 hr and at 24 hr (-1.8±1.8 ΔLog10 cfu/mL, mean±SD). Meropenem showed eradication of bacteria at 10 hr and reduction of bacteria at 24 hr (-1.3±1.9 ΔLog10 cfu/mL, mean±SD), (p=0.337 at 24 hr) (Table 4 and Fig. 1). When meropenem or vancomycin monotherapy was compared with the combination of meropenem plus vancomycin (M+V), ANOVA showed a statistically significant difference (p=0.004), and the difference between M+V and meropenem was significant, albeit without synergism (reduction of 4.8 vs. 1.8 log10 cfu/mL, respectively; p=0.003), while the difference between M+V and vancomycin was not (p=0.181) by Tukey's HSD test as a post hoc test (Fig. 2). Compared with ceftriaxone plus vancomycin and meropenem plus vancomycin, the combination of ceftriaxone plus vancomycin showed -4.0±1.2 ΔLog10 cfu/mL in CSF (mean±SD) and meropenem plus vancomycin showed -4.8±0.4 ΔLog10 cfu/mL (mean±SD), (p=0.054) (Table 4, Fig. 3). Both ceftriaxone plus vancomycin and meropenem plus vancomycin showed eradication in all 6 rabbits at 10 hr, however, meropenem plus vancomycin had a tendency to have superior activity against experimental strain at 24 hr (Table 3, Fig. 3). Compared with ceftriaxone plus vancomycin, meropenem plus vancomycin and ceftriaxone plus rifampin, only ceftriaxone plus rifampin showed eradication in all 6 rabbits at 24 hr (Table 3, Fig. 4).


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 - J. Korean Med. Sci. (2004)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2822258&req=5

Figure 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.
Mentions: CSF bacterial concentrations in each rabbit treatment group are shown in Fig. 1, 2, 3, and 4. Meropenem resulted in sterilization at 10 hr but regrowth was observed in all 6 rabbits at 24 hr (Table 3, Fig. 1). Meropenem plus vancomycin resulted in sterilization in all 6 rabbits at 10 hr, and regrowth was observed in 2 rabbits at 24 hr (Table 3 and Fig. 2). Meropenem therapy resulted in 5 log10 cfu/mL reduction in the bacterial concentration within 10 hr, but regrowth was observed at 24 hr (Table 4 and Fig. 1). Meropenem plus vancomycin resulted in 4.8 log10 cfu/mL reduction in the bacterial concentration within 10 hr. The effect persisted until 24 hr (Table 4 and Fig. 2), but regrowth was observed in 2 rabbits (Fig. 2). Compared with meropenem and ceftriaxone, ceftriaxone showed a less reduction of bacteria at 10 hr and at 24 hr (-1.8±1.8 ΔLog10 cfu/mL, mean±SD). Meropenem showed eradication of bacteria at 10 hr and reduction of bacteria at 24 hr (-1.3±1.9 ΔLog10 cfu/mL, mean±SD), (p=0.337 at 24 hr) (Table 4 and Fig. 1). When meropenem or vancomycin monotherapy was compared with the combination of meropenem plus vancomycin (M+V), ANOVA showed a statistically significant difference (p=0.004), and the difference between M+V and meropenem was significant, albeit without synergism (reduction of 4.8 vs. 1.8 log10 cfu/mL, respectively; p=0.003), while the difference between M+V and vancomycin was not (p=0.181) by Tukey's HSD test as a post hoc test (Fig. 2). Compared with ceftriaxone plus vancomycin and meropenem plus vancomycin, the combination of ceftriaxone plus vancomycin showed -4.0±1.2 ΔLog10 cfu/mL in CSF (mean±SD) and meropenem plus vancomycin showed -4.8±0.4 ΔLog10 cfu/mL (mean±SD), (p=0.054) (Table 4, Fig. 3). Both ceftriaxone plus vancomycin and meropenem plus vancomycin showed eradication in all 6 rabbits at 10 hr, however, meropenem plus vancomycin had a tendency to have superior activity against experimental strain at 24 hr (Table 3, Fig. 3). Compared with ceftriaxone plus vancomycin, meropenem plus vancomycin and ceftriaxone plus rifampin, only ceftriaxone plus rifampin showed eradication in all 6 rabbits at 24 hr (Table 3, Fig. 4).

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Disiases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, Korea.

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 a rabbit 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.

Show MeSH
Related in: MedlinePlus