meropenem and Meningitis--Pneumococcal

We describe unusual delayed recurrent episodes of ischemic stroke in a patient with initial good recovery from pneumococcal meningitis due to progressive arterial stenosis for over 3 months. We postulate that any of the following may have been responsible for his condition: widespread cerebral vasculopathy due to the effects of purulent material bathing the base of the brain, an immune-mediated para-infectious condition, or a rebound effect of the primary inflammatory reaction that was initially suppressed by dexamethasone. This case demonstrates that progressive arterial stenosis can evolve months after bacterial meningitis and should be recognized as a potential vascular complication.

Topics: Acetamides; Brain Damage, Chronic; Brain Ischemia; Ceftriaxone; Community-Acquired Infections; Constriction, Pathologic; Dexamethasone; Disease Progression; Drug Therapy, Combination; Humans; Linezolid; Male; Meningitis, Pneumococcal; Meropenem; Middle Aged; Oxazolidinones; Platelet Aggregation Inhibitors; Prednisolone; Recurrence; Thienamycins

Although the pneumococcal conjugate vaccine (PCV) has decreased the incidence of invasive pneumococcal disease (IPD) in children, cases of IPD caused by non-PCV serotypes have been increasing. Here, we report two cases of bacterial meningitis caused by meropenem-resistant Streptococcus pneumoniae; in both the cases, 13-valent PCV (PCV13) had been administered. The isolated S. pneumoniae strains were non-PCV13 serotype 35B and resistant to penicillin G, cefotaxime, and meropenem. In addition, multilocus sequence typing (MLST) revealed the sequence type (ST) to be 558. In case 1, a 6-month-old girl recovered without sequelae after antibiotic therapy comprising cefotaxime and vancomycin, whereas in case 2, a 9-month-old boy was treated with an empirical treatment comprising ceftriaxone and vancomycin administration. However, maintaining the blood concentration of vancomycin within the effective range was difficult, due to which the antibiotics were changed to panipenem/betamipron. During the treatment, he presented with seizures, which were effectively controlled with antiepileptic drugs. The rate of incidence of penicillin-susceptible IPD has been substantially increasing after the introduction of PCV. However, an upsurge in IPD cases due to multidrug-resistant (MDR) serotype 35B has been reported in countries where PCV13 was introduced before introducing in Japan. Moreover, an increase in the proportion of MDR serotype 35B and decrease in the susceptibility to broad-spectrum antimicrobials, including meropenem, have been reported. Hence, the number of meningitis cases caused by MDR serotype 35B/ST558 may increase in the future.

Topics: Anti-Bacterial Agents; beta-Alanine; Cefotaxime; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Male; Meningitis, Pneumococcal; Meropenem; Microbial Sensitivity Tests; Multilocus Sequence Typing; Pneumococcal Vaccines; Serotyping; Streptococcus pneumoniae; Thienamycins; Treatment Outcome

Topics: Ceftriaxone; Dexamethasone; Drug Resistance, Bacterial; Humans; Intensive Care Units; Male; Meningitis, Pneumococcal; Meropenem; Middle Aged; Molecular Typing; Moxifloxacin; Republic of Belarus; Streptococcus pneumoniae; Treatment Outcome

The absence of meningeal signs and symptoms is rare in patients with bacterial meningitis and may lead to a delay in diagnosis and treatment. Furthermore, the onset of bacterial meningitis associated with pneumocephalus is a rare complication of ear infections. We herein report a rare case of otogenic meningitis complicated by pneumocephalus that was initially missed due to the absence of typical meningeal signs and symptoms and later diagnosed correctly based on a thorough review of the patient's systems.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Dexamethasone; Humans; Male; Meningitis, Bacterial; Meningitis, Pneumococcal; Meropenem; Pneumocephalus; Thienamycins; Treatment Outcome; Vancomycin

A 61-year-old Japanese woman presented with a headache and appetite loss lasting for nine days and was admitted to our hospital, where she was diagnosed with pneumococcal meningitis associated with acute sphenoid sinusitis. While the administration of meropenem and dexamethasone ameliorated the meningitis, right third and sixth nerve palsy suddenly developed 10 days after admission. CT angiography subsequently demonstrated an aneurysm in the cavernous portion of the right internal carotid artery. This is the first reported case of sphenoid sinusitis simultaneously complicated by both pneumococcal meningitis and an infectious aneurysm in the intracavernous carotid artery.

Topics: Aneurysm, Infected; Angiography; Anti-Bacterial Agents; Carotid Artery, Internal; Cavernous Sinus; Dexamethasone; Embolization, Therapeutic; Female; Headache; Humans; Meningitis, Pneumococcal; Meropenem; Sphenoid Sinusitis; Spinal Puncture; Thienamycins; Treatment Outcome

Meropenem is a broad-spectrum carbapenem antibiotic that is highly active against the pathogens causing meningitis. The aims of this study was to determine the efficacies of meropenem alone and combined with rifampin against two Streptococcus pneumoniae strains with different susceptibility to beta-lactams using the guinea pig meningitis model and compare them with the standard ceftriaxone plus vancomycin therapy. All treatments except rifampin were bactericidal from 6 h. The addition of rifampin did not improve the activity of meropenem alone. Our results provide good evidence of the efficacy of meropenem in the treatment of penicillin- and cephalosporin-susceptible and -resistant pneumococcal meningitis similar to that of ceftriaxone plus vancomycin, suggesting that meropenem might be a good option in the management of this infection.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Colony Count, Microbial; Disease Models, Animal; Drug Therapy, Combination; Female; Guinea Pigs; Humans; Meningitis, Pneumococcal; Meropenem; Microbial Viability; Rifampin; Streptococcus pneumoniae; Thienamycins; Time Factors; Treatment Outcome; Vancomycin

The prevalence of penicillin-resistant Streptococcus pneumoniae (PRSP) meningitis has increased worldwide, particularly in East Asia and the United States. We recently experienced a case of PRSP meningitis that developed during frontofacial distraction. The patient was a 7-year-old girl with Crouzon disease who was treated by frontofacial monobloc/Le Fort IV minus glabellar osteotomy with quadruple internal distraction devices. Penicillin-resistant Streptococcus pneumoniae meningitis was diagnosed after surgery and treated successfully with meropenem (a carbapenem) at 120 mg kg d every 8 hours, ceftriaxone (a third-generation cephalosporin) at 100 mg kg d every 12 hours, and vancomycin (a glycopeptide) at 45 mg kg d every 6 hours. This case indicates that severe and fatal bacterial meningitis may occur as a postoperative complication due to multidrug-resistant bacteria indigenous to the nasal cavity after simultaneous osteotomy of the cranium and facial bone in intracraniofacial surgery, such as that for syndromic craniosynostosis and hypertelorbitism. In such cases, preventive strategies should include preoperative administration of pneumococcal vaccine, preoperative screening of nasal bacterial flora by nasal culture test, and prior administration of a carbapenem with good cerebrospinal fluid transfer or a third- or fourth-generation cephem covering PRSP. Postoperatively, suspected meningitis may be treated with a combination of the 3 drugs used in our case, in parallel with emergency cephalic contrast computed tomography and culture tests of blood and cerebrospinal fluid. Our experience suggests that these measures will facilitate a successful outcome in frontofacial distraction osteogenesis.

Topics: Anti-Bacterial Agents; Ceftriaxone; Child; Craniofacial Dysostosis; Drug Combinations; Female; Follow-Up Studies; Frontal Bone; Humans; Meningitis, Pneumococcal; Meropenem; Osteogenesis, Distraction; Osteotomy; Osteotomy, Le Fort; Penicillin Resistance; Streptococcus pneumoniae; Surgical Wound Infection; Thienamycins; Tomography, X-Ray Computed; Treatment Outcome; Vancomycin

Meropenem is a carbapenem antibiotic that is highly active against the pathogens causing meningitis. Results with meropenem in the experimental rabbit model of penumococcal meningitis have been controversial, and the possible role of renal dehydropeptidase I in meropenem efficacy has been suggested. The aim of this study was to determine the efficacy of meropenem in two meningitis models and the possible influence of the animal model over results. Two strains of Streptococcus pneumoniae with different susceptibility to beta-lactams have been used in a guinea pig model and the classical rabbit meningitis model. Meropenem was bactericidal at 6 h in the guinea pig model against both strains with a reduction of >4 log ufc/ml. In the rabbit model it was bactericidal at 6 h against the susceptible strain, but against the resistant 3/8 therapeutical failures were recorded at 6 h, being bactericidal at 24 h. In conclusion, meropenem has shown bactericidal activity in both experimental models. This work emphasises the importance of an adequate election of the animal model for the appropriate development of studies of antimicrobial efficacy. We believe that guinea pig should be considered the best choice among laboratory animal species when assessing meropenem efficacy.

Topics: Animals; Cephalosporin Resistance; Cephalosporins; Disease Models, Animal; Guinea Pigs; Meningitis, Bacterial; Meningitis, Pneumococcal; Meropenem; Microbial Sensitivity Tests; Rabbits; Streptococcus pneumoniae; Thienamycins

To determine the probability of meropenem (Merrem, AstraZeneca Pharmaceuticals L.P., Wilmington, DE, USA) and cefotaxime (Claforan, Aventis Pharmaceuticals Inc., Bridgewater, NJ, USA) achieving bactericidal exposures in the cerebrospinal fluid against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae.. A 5,000-patient Monte Carlo simulation in a population of 10-year-old children with meningitis was conducted. Pediatric pharmacokinetic data were derived from the literature. Pathogen minimum inhibitory concentrations (MICs) were obtained from common bacteria that had caused meningitis collected during pediatric clinical trials. Time above the MIC exposures in the cerebrospinal fluid was calculated. Bactericidal exposure or probability of target attainment was defined as 40% and 50% time above the MIC for meropenem and cefotaxime, respectively. High cumulative fractions of responses were defined as >90% probability of target attainment against the populations of bacteria.. Meropenem was calculated to achieve 94.7%, 94.3%, and 96.1% cumulative fractions of response against S. pneumoniae, H. influenzae, and N. meningitidis, respectively. Cefotaxime only achieved a high likelihood of bactericidal attainment against N. meningitidis (91.6%). Against S. pneumoniae and H. influenzae, cefotaxime was only calculated to achieve 84.3% and 84.8% cumulative fractions of response, respectively.. In a simulated population of 10-year-old children, meropenem had a high likelihood of attaining bactericidal exposures in the cerebrospinal fluid. Cefotaxime had a >90% cumulative fraction of response against only N. meningitidis. Therefore, at the doses simulated, meropenem may be a more appropriate empiric choice for the treatment of bacterial meningitis in pediatric patients presumed to be caused by these pathogens until culture and susceptibility data are available.

Topics: Anti-Bacterial Agents; Body Weight; Cefotaxime; Child; Computer Simulation; Dose-Response Relationship, Drug; Humans; Meningitis, Bacterial; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Meropenem; Monte Carlo Method; Thienamycins

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.

Topics: Animals; Anti-Bacterial Agents; Cerebrospinal Fluid; Disease Models, Animal; Drug Resistance, Microbial; Humans; Male; Meningitis, Pneumococcal; Meropenem; Penicillins; Rabbits; Streptococcus pneumoniae; Thienamycins; Time Factors

Streptococcus pneumoniae is one of the leading causes of acute bacterial meningitis and the emergence of antibiotic resistant pneumococci is an increasing problem worldwide. In this report, a 22-years-old woman was presented with pneumococcal meningitis occurring twice in a 5 months period. After the first meningitis attack, the patient had been vaccinated by 23-valent polysaccharide vaccine but the illness has relapsed. Although S. pneumoniae which was isolated from the patient has been found intermediate resistant to penicillin and susceptible to ceftriaxone by E-test, the patient could be treated only with meropenem. The case has been presented and discussed for ceftriaxone failure in spite of in-vitro susceptibility. On the other hand, this case indicated that vaccination might fail to prevent recurrence.

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Female; Humans; Immunotherapy, Active; Meningitis, Pneumococcal; Meropenem; Penicillins; Pneumococcal Vaccines; Secondary Prevention; Streptococcus pneumoniae; Thienamycins

The aim of the present study was to investigate the potential synergy between meropenem and levofloxacin in vitro and in experimental meningitis and to determine the effect of meropenem on levofloxacin-induced resistance in vitro. Meropenem increased the efficacy of levofloxacin against the penicillin-resistant pneumococcal strain KR4 in time-killing assays in vitro and acted synergistically against a second penicillin-resistant strain WB4. In the checkerboard, only an additive effect (FIC indices: 1.0) was observed for both strains. In cycling experiments in vitro, levofloxacin alone led to a 64-fold increase in the MIC for both strains after 12 cycles. Addition of meropenem in sub-MIC concentrations (0.25 x MIC) completely inhibited the selection of levofloxacin-resistant mutants in WB4 after 12 cycles. In KR4, the addition of meropenem led to just a twofold increase in the MIC for levofloxacin after 12 cycles. Mutations detected in the genes encoding for topoisomerase IV (parC) and gyrase (gyrA) confirmed the levofloxacin-induced resistance in both strains. Addition of meropenem was able to completely suppress levofloxacin-induced mutations in WB4 and led to only one mutation in parE in KR4. In experimental meningitis, meropenem, given in two doses (2 x 125 mg/kg), produced a good bactericidal activity (-0.45 Deltalog10 cfu/ml.h) comparable to one dose (1 x 10 mg/kg) of levofloxacin (-0.44 Deltalog10 cfu/ml.h) against the penicillin-resistant strain WB4. Meropenem combined with levofloxacin acted synergistically (-0.93 Deltalog10 cfu/ml.h), sterilizing the CSF of all rabbits.

Topics: Animals; Disease Models, Animal; DNA, Bacterial; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Levofloxacin; Male; Meningitis, Pneumococcal; Meropenem; Microbial Sensitivity Tests; Ofloxacin; Penicillin Resistance; Polymerase Chain Reaction; Rabbits; Reference Values; Sensitivity and Specificity; Streptococcus pneumoniae; Thienamycins

Topics: Cefotaxime; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Meningitis, Pneumococcal; Meropenem; Microbial Sensitivity Tests; Severity of Illness Index; Spinal Puncture; Streptococcus pneumoniae; Thienamycins; Treatment Failure; Vancomycin

In a rabbit model of meningitis caused by a pneumococcus highly resistant to penicillin (MIC, 4 microg/ml), meropenem, a broad-spectrum carbapenem, was bactericidal (-0.48+/-0.14 deltalog10 cfu/ml h) and slightly superior to ceftriaxone (-0.34+/-0.23 deltalog10 cfu/ml x h) and vancomycin (-0.39+/-0.19 deltalog10 cfu/ml x h). Although the combination of vancomycin with ceftriaxone was significantly more active than ceftriaxone alone (-0.55+/-0.19 deltalog10 cfu/ml x h), only an insignificant gain was observed by the addition of vancomycin to meropenem (-0.55+/-0.28 deltalog10 cfu/ml x h).

Topics: Animals; Ceftriaxone; Cephalosporins; Colony Count, Microbial; Disease Models, Animal; Drug Therapy, Combination; Meningitis, Pneumococcal; Meropenem; Microbial Sensitivity Tests; Penicillin Resistance; Rabbits; Streptococcus pneumoniae; Thienamycins; Vancomycin

The activities of meropenem, imipenem, ceftriaxone, and vancomycin were evaluated against 80 penicillin-susceptible and -resistant Streptococcus pneumoniae strains. Meropenem, imipenem, ceftriaxone, and vancomycin MICs at which 90% of the isolates are inhibited were 0.5, 0.25, 1, and 0.25 microg/ml, respectively. Against penicillin-resistant strains, the best killing activity at cerebrospinal fluid concentrations was obtained with imipenem and ceftriaxone-vancomycin. However, while the killing activity of imipenem was significantly greater than that of meropenem, no significant difference was observed between the activities of meropenem and ceftriaxone-vancomycin.

Topics: Anti-Bacterial Agents; Carbapenems; Ceftriaxone; Cephalosporins; Child; Drug Therapy, Combination; Humans; Imipenem; Meningitis, Pneumococcal; Meropenem; Microbial Sensitivity Tests; Penicillin Resistance; Streptococcus pneumoniae; Thienamycins; Vancomycin

Topics: Child, Preschool; Drug Resistance, Microbial; Drug Resistance, Multiple; Humans; Male; Meningitis, Pneumococcal; Meropenem; Thienamycins

In-vitro susceptibility of 299 Neisseria meningitidis and 157 Streptococcus pneumoniae strains from meningitis patients in The Netherlands in 1993 and 1994 to meropenem was determined using the Etest. Susceptibility to penicillin, ceftriaxone, and chloramphenicol was also determined. Rifampicin susceptibility was additionally tested for N. meningitidis. Of the meningococci, 4.3% were of intermediate resistance to penicillin and 0.3% were resistant to rifampicin. One pneumococcal isolate (0.6%) was of intermediate resistance to penicillin. All strains were susceptible to meropenem. We conclude that meropenem is in vitro highly active against N. meningitidis and S. pneumoniae.

Topics: Anti-Bacterial Agents; Ceftriaxone; Chloramphenicol; Humans; Meningitis, Meningococcal; Meningitis, Pneumococcal; Meropenem; Microbial Sensitivity Tests; Neisseria meningitidis; Netherlands; Penicillins; Streptococcus pneumoniae; Thienamycins

Topics: Acute Disease; Anti-Bacterial Agents; Anti-Inflammatory Agents; Bacteremia; Cerebrospinal Fluid; Clarithromycin; Dexamethasone; Drug Therapy, Combination; Female; Humans; Infant; Infusions, Intravenous; Meningitis, Pneumococcal; Meropenem; Microbial Sensitivity Tests; Otitis Media; Streptococcus pneumoniae; Thienamycins

The most appropriate therapy for meningitis caused by Streptococcus pneumoniae strains resistant to the extended-spectrum cephalosporins is unknown. We evaluated ceftriaxone, vancomycin, and rifampin alone and in different combinations and meropenem, cefpirome, and clinafloxacin alone in the rabbit meningitis model. Meningitis was induced in rabbits by intracisternal inoculation of one of two pneumococcal strains isolated from infants with meningitis (ceftriaxone MICs, 4 and 1 microgram/ml, respectively). Two doses, 5 h apart, of each antibiotic were given intravenously (except that ceftriaxone was given as one dose). Cerebrospinal fluid bacterial concentrations were measured at 0, 5, 10, and 24 h after therapy was started. Clinafloxacin was the most active single agent against both strains. Against the more resistant strain, ceftriaxone or meropenem alone was ineffective. The combination of vancomycin and ceftriaxone was synergistic, suggesting that this combination might be effective for initial empiric therapy of pneumococcal meningitis until results of susceptibility studies are available.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Cefpirome; Ceftriaxone; Cephalosporins; Disease Models, Animal; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Fluoroquinolones; Male; Meningitis, Pneumococcal; Meropenem; Microbial Sensitivity Tests; Penicillin Resistance; Quinolones; Rabbits; Rifampin; Thienamycins; Vancomycin