meropenem and Meningitis--Bacterial

A 39-year-old previously healthy man was referred to our hospital because of acute onset of fever and consciousness disturbance. Neurological examinations revealed deteriorated consciousness, nuchal rigidity and Kernig's sign. A lumbar puncture yielded clouded fluid with a WBC 1,012/μl (polynuclear cell 96%), 147.3 mg/dl of protein, 44 mg/dl of glucose and Gram positive cocci. At first, he was treated with ceftriaxon and ampicillin. At Day 2, meropenem was added. Streptococcus agalactiae was isolated from blood and cerebrospinal fluid. He responded promptly to antimicrobial therapy, and within 2 days, he became lucid and afebrile. S. agalactiae was sensitive to ceftriaxone, ampicillin and meropenem. After Day 3, he was treated with meropenem only. We diagnosed his condition as S. agalactiae meningitis and was discharged from our hospital at Day 18. Many cases of S. agalactiae meningitis are known to occur in neonates, pregnant women, elderly, and persons with underlying disease such as diabetes, malignant disorders, liver dysfunction. But cases occurring in a previously healthy adult are rare. Neurologists should be aware that S. agalactiae may be cause bacterial meningitis in a previously healthy adults.

Topics: Adult; Ampicillin; Anti-Bacterial Agents; Ceftriaxone; Consciousness Disorders; Drug Therapy, Combination; Fever; Humans; Immunocompetence; Male; Meningitis, Bacterial; Meropenem; Streptococcal Infections; Streptococcus agalactiae; Treatment Outcome

The zoonotic pathogen Campylobacter fetus is a rare cause of bacterial meningitis. Little is known about the clinical characteristics, predisposing factors and outcome of C fetus meningitis in adults.We report cases of C fetus meningitis in a nationwide cohort study of adult bacterial meningitis patients in the Netherlands and performed a review of the literature.Two patients with C fetus meningitis were identified from January 2006 through May 2015. The calculated annual incidence was 0.02 per million adults. Combined with the literature, we identified 22 patients with a median age of 48 years. An immunocompromised state was present in 16 patients (73%), mostly due to alcoholism (41%) and diabetes mellitus (27%). The source of infection was identified in 13 out of 19 patients (68%), consisting of regular contact with domestic animals in 5 and working on a farm in 4. Recurrent fever and illness was reported in 4 patients (18%), requiring prolonged antibiotic treatment. Two patients died (9%) and 3 survivors (15%) had neurological sequelae.C fetus is a rare cause of bacterial meningitis and is associated with an immunocompromised state. Based on the apparent slow clinical response seen in this limited number of cases, the authors of this study recommend a prolonged course of antimicrobial therapy when C fetus is identified as a causative agent of bacterial meningitis. Cases appeared to do best with carbapenem therapy.

Topics: Adult; Anti-Bacterial Agents; Campylobacter fetus; Campylobacter Infections; Female; Humans; Incidence; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Netherlands; Thienamycins

Community acquired bacterial meningitis due to extended spectrum β lactamase-producing Escherichia coli is very rare. We report the case of a 72-year-old woman being treated for longstanding diabetes mellitus. She developed lower back pain accompanied by elevated body temperature, and was transported to the emergency unit in our hospital five days later because of impaired consciousness. An abdominal plane CT showed acute pyelonephritis and a brain MRI showed inflammatory exudate in the posterior horn of her bilateral ventricles. A lumbar puncture was performed, and examination of the cerebrospinal fluid revealed a marked elevation in her cell count (polymorphonuclear leukocytes dominant) that we diagnosed as bacterial meningitis. Initially, she was treated with intravenous meropenem, ceftriaxon, and vancomycin. Extended spectrum β lactamase-producing Escherichia coli were then detected in her urinary and blood cultures, and the antibiotics were changed to intravenous meropenem, gentamicin, and intrathecal gentamicin. Her clinical symptoms improved, but her inflammatory reaction was prolonged and we detected spondylitis. She was then treated with levofloxacin, and the inflammatory reaction improved. Extended spectrum β lactamase-producing Escherichia coli should be taken into consideration as a cause of community acquired bacterial meningitis.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Community-Acquired Infections; Escherichia coli; Escherichia coli Infections; Female; Gentamicins; Humans; Infusions, Intravenous; Meningitis, Bacterial; Meropenem; Thienamycins; Treatment Outcome

Meropenem is a carbapenem antibiotic approved by the US Food and Drug Administration for the treatment of complicated skin and skin-structure infections, complicated intra-abdominal infections, and pediatric bacterial meningitis (in patients >or=3 months of age). In clinical trials, it also has shown efficacy as initial empirical therapy for the treatment of nosocomial pneumonia. Unlike other beta-lactam antibiotics, including third-generation cephalosporins, carbapenems have shown activity against extended-spectrum beta-lactamase-producing and AmpC chromosomal beta-lactamase-producing bacteria. Compared with imipenem, meropenem is more active against gram-negative pathogens and somewhat less active against gram-positive pathogens, and it does not require coadministration of a renal dehydropeptidase inhibitor. In most comparative trials, clinical and bacteriological response rates with imipenem and meropenem were similar. Compared with clindamycin/tobramycin, meropenem is associated with a reduced length of hospital stay and a shorter duration of therapy among patients with complicated intra-abdominal infections. Meropenem is well tolerated by children and adults and has an acceptable safety profile. Alternative meropenem dosing strategies for the optimization of outcomes are under investigation.

Topics: Abdominal Abscess; Bacteria; Bacterial Infections; Cross Infection; Humans; Infant; Meningitis, Bacterial; Meropenem; Pneumonia; Skin Diseases, Bacterial; Thienamycins

Antimicrobial resistance is increasing among bacterial pathogens. In particular, organisms producing extended spectrum beta-lactamase enzymes (ESBLs) and AmpC chromosomal beta-lactamase enzymes are resistant to third generation cephalosporins and pose a formidable challenge in the management of seriously ill patients. Carbapenems are a class of broad-spectrum antibiotics with stability against ESBL and AmpC chromosomal beta-lactamases. They are well tolerated by patients. This review will examine the pharmacokinetic and pharmacodynamic properties of two carbapenems imipenem and meropenem and discuss their clinical use in children. References are limited to the English language and extend back to 1980. Sources include computerized databases such as MEDLINE searched using PubMed, and bibliographies of recent articles and books. Approximately 50% of the articles initially reviewed are included in the bibliography. Carbapenems are efficacious in the treatment of a variety of bacterial infections including meningitis, pneumonia, intraabdominal infections, bone, joint and urinary tract infections. The broad spectrum activity and comparatively low toxicity of carbapenems make them valuable therapeutic agents in the treatment of seriously ill patients with bacterial infections. These agents should be used judiciously in order to minimize the risk for development of carbapenem-resistant pathogens.

Topics: Child; Humans; Imipenem; Meningitis, Bacterial; Meropenem; Neutropenia; Pneumonia, Bacterial; Thienamycins

Fusobacterium necrophorum, an anaerobic, gram-negative rod, belongs to the physiological flora of the oropharynx. It causes Lemierre's syndrome characterized by oropharyngeal infection, septic thrombophlebitis of the neck, in particular of the internal jugular vein, and metastatic abscesses, predominantly in the lungs. Rarely, and mainly in children, it causes meningitis. Here we report the clinical course of a 25-year-old woman with F. necrophorum meningitis. She presented with incomplete, right third nerve palsy. Within a few days, she developed fever, meningism and progressive reduction of vigilance. Cerebrospinal fluid analysis showed typical signs of bacterial meningitis. After the identification of F. necrophorum, the antibiotic treatment was changed to meropenem, which led to continuous improvement of the clinical symptoms. Due to persistent signs of inflammation in the CSF, metronidazole was added to the antibiotic regime. This case report demonstrates that F. necrophorum should always be considered in the diagnostic workup of bacterial meningitis in adults.

Topics: Adult; Anti-Bacterial Agents; Blood Glucose; Cerebrospinal Fluid Proteins; Diagnosis, Differential; Drug Therapy, Combination; Female; Fusobacterium necrophorum; Humans; Lactic Acid; Leukocyte Count; Lung Abscess; Meningitis, Bacterial; Meropenem; Metronidazole; Oculomotor Nerve Diseases; Otitis Media; Pharyngitis; Sepsis; Syndrome; Thienamycins

The tolerability of the 2 most frequently used carbapenems, imipenem/cilastatin and meropenem, is reviewed. Both of these drugs, but especially imipenem, are potentially neurotoxic and may cause seizures if overdosed relative to renal function and/or bodyweight. The therapeutic margin is considerably narrower with imipenem/cilastatin which cannot be given at doses required for treatment of bacterial meningitis. Meropenem on the other hand, is considerably less prone to cause seizures and its tolerability and efficacy are well documented in 3 relatively large, controlled studies in adults and children with meningitis. They showed that meropenem was as effective and well tolerated as cefotaxime or ceftriaxone. Another potential advantage of meropenem over imipenem/cilastatin is that it can be given intravenously at a high rate without increased risk of nausea or vomiting. An obvious reason for using a carbapenem instead of a cephalosporin for empirical treatment of life-threatening infections is that both imipenem/cilastatin and meropenem have a broader spectrum of activity. They are also more resistant to hydrolysis by the most common beta-lactamases, including the class I cephalosporinase frequently produced by Enterobacter spp. and Pseudomonas spp. and the extended spectrum enzymes, now commonly found in Escherichia coli and Klebsiella spp.

Topics: Adult; Cephalosporins; Child; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Tolerance; Humans; Imipenem; Meningitis, Bacterial; Meropenem; Risk Assessment; Seizures; Thienamycins

Three broad-spectrum antibiotics are reviewed, each from a different class. Meropenem is closely related to imipenem and was recently approved for use in children. Its advantages over imipenem include greater activity against gram-negative bacteria and lack of association with seizures. Cefepime is a fourth generation cephalosporin with the gram-positive activity of cefotaxime and the gram-negative spectrum of ceftazidime. Trovafloxacin is a fluoroquinolone with an exceptionally broad antibacterial spectrum. Meropenem is approved for use in children, cefepime is approved for use in adults only, and trovafloxacin is still undergoing clinical trials. These agents should be reserved for treatment of serious infections, especially those in immunocompromised patients or polymicrobial infections.

Topics: Anti-Infective Agents; Cefepime; Cephalosporins; Child; Fluoroquinolones; Humans; Meningitis, Bacterial; Meropenem; Naphthyridines; Thienamycins

Meropenem is a new beta-lactam carbapenem antibiotic that appears to be promising in the treatment of hospitalized infants and children with serious infections. It has broad-spectrum activity against microorganisms, including most of the major aerobic (gram-negative and gram-positive) and anaerobic pathogens that cause serious bacterial infections in neonates and children. In addition, its pharmacokinetic profile makes possible parenteral administration every 8 hours. Several studies have demonstrated that meropenem is an effective and safe treatment for infants and children with serious pediatric infections (e.g., urinary tract infections, pneumonia, sepsis, intraabdominal infections, and skin and soft-tissue infections), bacterial meningitis, and cystic fibrosis. The results of further studies of the use of meropenem in the treatment of high-risk seriously ill infants and children are awaited with interest.

Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Cystic Fibrosis; Female; Hospitalization; Humans; Infant; Infant, Newborn; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Thienamycins

Carbapenems are active beta-lactam antibiotics versus most of the gram positive and gram negative microorganisms and anaerobes although their activity is lacking in the case of Staphylococcus sp. resistant to methicillin, Enterococcus faecium and Streptococcus pneumoniae with high resistance to penicillin and some gram negative bacilli which naturally produce an methaloenzyme able to hydrolyze them such as Stenotrophomonas maltophilia. Imipenem, the first synthetized carbapenem requires administration with cilastatin to avoid inactivation by renal dehydropeptidase 1. Meropenem does not require being taken with the renal enzyme inhibitor, with its activity being similar to that of imipenem. In abdominal infection the carbapenems have shown to be the authentic monotherapy in this type of infections being as effective as the different schedules of antibiotic associations normally used. Treatment with carbapenems in bacterial meningitis should be currently limited to the cases produced by gram negative bacilli producers of wide spectrum beta-lactamases (WSBL), cases of meningitis by Pseudomonas aeruginosa or gram negative bacilli producers of inducible cephalosporinase. Meropenem is the carbapenem of choice probably in these cases because the carbapenems are often the only active antibiotics and meropenem, specifically, does not have the risk of convulsions observed with imipenem-cilastatin. The carbapenems have shown to be useful in skin and soft tissue infections as well as in obstetric and gynecologic infections as monotherapy similar to the schedules of the currently used antibiotic associations. In the case of nosocomial pneumonias, all the studies have evaluated the carbapenems in monotherapy as useful and effective, specially in the case of pneumonia by gram negative bacilli. Finally, in non filiated nosocomial sepsis and specially in the case of neutropenic patients, the use of carbapenems is particularly attractive in gram negative sepsis in intensive care units. The appearance in the last few years of strains of gram negative bacilli, producers of wide spectrum beta-lactamase or stable repressed hyperproducers of class I chromosomic cephalosporinase, as well as other multiresistant gram negative bacilli, such as Acinetobacter baumanii make the carbapenems, in many cases, the only effective antibiotic in this type of infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Cross Infection; Drug Therapy, Combination; Humans; Imipenem; Meningitis, Bacterial; Meropenem; Pneumonia, Bacterial; Skin Diseases, Infectious; Thienamycins

Topics: Carbapenems; Child; Child, Preschool; Humans; Imipenem; Infant; Infant, Newborn; Meningitis, Bacterial; Meropenem; Thienamycins

Meropenem and imipenem are carbapenems which are distinguishable from all other currently available beta-lactam antibiotics by breadth of antibacterial spectrum and stability to beta-lactamases, but can be differentiated one from another. Meropenem is relatively stable to human renal dehydropeptidase-I (DHP-I); it does not require to be co-administered with cilastatin and consequently, unlike imipenem, will be administered as a single agent. In vitro both meropenem and imipenem are active against almost all clinically important aerobic and anaerobic bacteria. Differences in potency are seen but few may be of clinical significance: imipenem is more active against enterococci and meropenem is more active against Pseudomonas aeruginosa, Pseudomonas cepacia, Haemophilus influenzae and Proteus, Morganella and Providencia species. The primary target of imipenem is PBP2 in P. aeruginosa whilst meropenem has high affinity for both PBP2 and 3; this may contribute to greater potency against this organism. Laboratory evaluations predict that meropenem will not be seizurogenic, which combined with activity against likely pathogens, identified its potential for the treatment of bacterial meningitis. This has been investigated in a guinea-pig model in which meropenem exhibited potent activity against the common meningeal pathogens and also infections caused by penicillin-resistant Streptococcus pneumoniae or Listeria monocytogenes. Clinical experience will determine the significance of these differences.

Topics: Animals; Bacteria; Drug Stability; Humans; Imipenem; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Structure-Activity Relationship; Thienamycins

Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem, a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking.. To determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS).. Data were collected in two recently conducted studies, i.e. NeoMero-1 (neonatal LOS) and NeoMero-2 (neonatal meningitis). Optimally timed plasma samples (n = 401) from 167 patients and opportunistic CSF samples (n = 78) from 56 patients were analysed.. A one-compartment model with allometric scaling and fixed maturation gave adequate fit to both plasma and CSF data; the CL and volume (standardized to 70 kg) were 16.7 (95% CI 14.7, 18.9) L/h and 38.6 (95% CI 34.9, 43.4) L, respectively. CSF penetration was low (8%), but rose with increasing CSF protein, with 40% penetration predicted at a protein concentration of 6 g/L. Increased infusion time improved plasma target attainment, but lowered CSF concentrations. For 24 patients with culture-proven Gram-negative LOS, pharmacodynamic target attainment was similar regardless of the test-of-cure visit outcome.. Simulations showed that longer infusions increase plasma PTA but decrease CSF PTA. CSF penetration is worsened with long infusions so increasing dose frequency to achieve therapeutic targets should be considered.

Topics: Anti-Bacterial Agents; Europe; Female; Gram-Negative Bacterial Infections; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Male; Meningitis, Bacterial; Meropenem; Monte Carlo Method; Neonatal Sepsis; Sepsis

Meropenem is important for management of postneurosurgical meningitis, but the data about its penetration into cerebrospinal fluid (CSF) are inadequate. This prospective, open-label study investigated the pharmacokinetic profile of meropenem in patients with postneurosurgical meningitis, especially its CSF penetration.. A total of 82 patients with postneurosurgical meningitis were included to receive meropenem intravenously according to a regimen of 2 g every 8 hours, 1 g every 8 hours, or 1 g every 6 hours. After infusion of 4 doses, blood and CSF samples were collected simultaneously at predefined time points. The high-performance liquid chromatography ultraviolet method was used to determine the concentration of meropenem.. The peak meropenem concentration in blood and CSF was 43.2 ± 5.3 and 2.4 ± 0.3 mg/L in the group who received 2 g every 8 hours; 28.9 ± 2.7 and 1.2 ± 0.2 mg/L in the group who received 1g every 8 hours; and31.5 ± 3.4 and 1.6 ± 0.2 mg/L in the group who received 1g every 6 hours. The maximal percent penetration into CSF was 17.6% ± 7.3%, 14.3% ± 1.7%, and 30.9% ± 24.2%, respectively.. Dosing regimens of meropenem 1 g every 6 hours and 2 g every 8 hours provided higher CSF penetration than 1 g every 8 hours. A higher dose and shorter dosing interval of meropenem may be more useful for clearance of pathogens.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Prospective Studies; Thienamycins; Treatment Outcome

Meropenem is used to manage postneurosurgical meningitis, but its population pharmacokinetics (PPK) in plasma and cerebrospinal fluid (CSF) in this patient group are not well-known. Our aims were to (i) characterize meropenem PPK in plasma and CSF and (ii) recommend favorable dosing regimens in postneurosurgical meningitis patients. Eighty-two patients were enrolled to receive meropenem infusions of 2 g every 8 h (q8h), 1 g q8h, or 1 g q6h for at least 3 days. Serial blood and CSF samples were collected, and concentrations were determined and analyzed via population modeling. Probabilities of target attainment (PTA) were predicted via Monte Carlo simulations, using the target of unbound meropenem concentrations above the MICs for at least 40% of dosing intervals in plasma and at least of 50% or 100% of dosing intervals in CSF. A two-compartment model plus another CSF compartment best described the data. The central, intercentral/peripheral, and intercentral/CSF compartment clearances were 22.2 liters/h, 1.79 liters/h, and 0.01 liter/h, respectively. Distribution volumes of the central and peripheral compartments were 17.9 liters and 3.84 liters, respectively. The CSF compartment volume was fixed at 0.13 liter, with its clearance calculated by the observed drainage amount. The multiplier for the transfer from the central to the CSF compartment was 0.172. Simulation results show that the PTAs increase as infusion is prolonged and as the daily CSF drainage volume decreases. A 4-hour infusion of 2 g q8h with CSF drainage of less than 150 ml/day, which provides a PTA of >90% for MICs of ≤8 mg/liter in blood and of ≤0.5 mg/liter or 0.25 mg/liter in CSF, is recommended. (This study has been registered at ClinicalTrials.gov under identifier NCT02506686.).

Topics: Adult; Aged; Anti-Bacterial Agents; Brain Injuries, Traumatic; Brain Neoplasms; Drug Administration Schedule; Female; Gram-Negative Bacteria; Humans; Infusions, Intravenous; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Neurosurgery; Postoperative Complications; Prospective Studies; Thienamycins

The aim of this study was to assess the efficacy, safety, and concentration of meropenem in cerebrospinal fluid when meropenem (2 g every 8 h) was administered to Japanese adult patients with bacterial meningitis. Five Japanese patients (mean age 60.6 years [range 35-71]) were enrolled. Infection with Streptococcus pneumoniae (three patients), Streptococcus salivarius (one patient), and Staphylococcus aureus (one patient) was confirmed by cerebrospinal fluid culture. Meropenem (2 g every 8 h) was administered to all five patients. Treatment duration ranged from 14 to 28 days (mean 22.6 days). All the patients were successfully treated. The concentration of meropenem in cerebrospinal fluid ranged from 0.27 to 6.40 μg/ml up to 8.47 h and was over 1 μg/ml 3 h after starting meropenem infusion. In each patient, the present study confirmed for the first time that the concentration of meropenem in cerebrospinal fluid exceeded the minimal inhibitory concentration for these pathogens. Eleven clinical and laboratory adverse events considered to be related to meropenem were observed in all patients, but no serious adverse event and no discontinuance of treatment due to adverse events occurred. Thus meropenem appeared to be a well-tolerated and effective agent for Japanese adult patients with bacterial meningitis. 2 g every 8 h of meropenem was delivered to CSF and its concentration was exceed in MICs for the detected pathogens.

Topics: Adult; Aged; Anti-Bacterial Agents; Female; Humans; Japan; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Middle Aged; Staphylococcal Infections; Staphylococcus; Thienamycins; Treatment Outcome

This study examined the pharmacokinetics and pharmacodynamics of meropenem in cerebrospinal fluid (CSF). Meropenem (0.5 g every 8 h) was administered by 0.5-h infusion to six neurosurgical patients. Lumbar CSF and venous blood samples were obtained at 0.5-16 h after the start of the first infusion. Drug concentrations in the CSF and plasma were analyzed pharmacokinetically and used for a Monte Carlo simulation with the minimum inhibitory concentration (MIC) data of clinical isolates in Japan. Meropenem penetrated into the CSF with the area under the drug concentration-time curve ratio of 0.10 +/- 0.03 (mean +/- SD) and the repeated infusions caused the drug concentration in the CSF to accumulate slightly. Against Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, and Escherichia coli isolates, 0.5 g q8h achieved a >90% probability of pharmacodynamic target (50% of the time above MIC) attainment, and 1 g q8h was needed for a >90% probability of target (100% of the time above MIC) attainment. However, against Pseudomonas aeruginosa, 2 g q8h achieved a lower probability of target attainment. These results should help us to better elucidate the pharmacokinetics of meropenem in the cerebrospinal space while also helping us to choose the appropriate drug dosages for the management of bacterial meningitis.

Topics: Anti-Bacterial Agents; Area Under Curve; Female; Humans; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Neurosurgical Procedures; Thienamycins

To compare the efficacy and safety of meropenem with cefotaxime for the treatment of infants and children with bacterial meningitis.. Infants and children with strongly suspected or documented bacterial meningitis were randomly assigned in a prospective multicenter study to receive either meropenem or cefotaxime. Patients were assessed at the end of therapy and at 5 to 7 weeks and 5 to 7 months after the end of treatment for the presence of neurologic and sensory neural sequelae.. A total of 258 children were randomized to either treatment group. A further 8 patients with suspected pneumococcal meningitis were treated with meropenem without randomization. Of the randomized patients 154 were fully evaluable, 79 in the meropenem group and 75 in the cefotaxime group. At the end of treatment there were no significant differences in clinical outcome between the two treatment groups. Clinical cure with or without sequelae was achieved in 97 and 96% of the meropenem- and cefotaxime-treated patients, respectively. At the end of treatment and at 5 to 7 weeks, 46 and 54% of meropenem patients were cured with no sequelae, respectively. Corresponding results for cefotaxime patients were 56 and 58%. All pathogens were eradicated. In total 37 patients had seizures during treatment, 15 (12%) in the meropenem and 22 (17%) in the cefotaxime group. None of the seizures was considered to be drug-related.. This trial shows that meropenem is suitable therapy for bacterial meningitis in infants and children and that it offers an efficacy and safety profile similar to that of cefotaxime.

Topics: Cefotaxime; Cephalosporins; Child; Child, Preschool; Female; Humans; Infant; Male; Meningitis, Bacterial; Meropenem; Prospective Studies; Single-Blind Method; Thienamycins; Treatment Outcome

Meropenem was used in the treatment of 15 newborns (8 preterm) with sepsis, pneumonia or meningitis by intravenous infusion of 15-20 mg/kg daily divided to 3 equal doses. Clinical improvement was achieved in all the cases. No side effects were recorded.

Topics: Bacterial Infections; Dose-Response Relationship, Drug; Humans; Infant, Newborn; Infant, Premature, Diseases; Meningitis, Bacterial; Meropenem; Pneumonia, Bacterial; Sepsis; Thienamycins

Broad-spectrum cephalosporins are drugs of choice for the treatment of meningitis in communities which can afford them. The emergence of cephalosporin-resistant pneumococci demands the clinical trial of alternate agents. Carbapenems are active against the bacteria causing meningitis, but the use of imipenem-cilastatin was frustrated by drug-associated seizures. The safety and efficacy of meropenem, a new carbapenem, were compared to those of cefotaxime in a prospective randomized trial of 190 children with bacterial meningitis. Seizures occurred within 24 h before antibiotic therapy in 16 of 98 patients (16%) randomized to receive meropenem and in 6 of 92 patients (7%) randomized to receive cefotaxime. In patients without seizures before therapy, seizures occurred during therapy in 5 of 82 patients (6%) receiving meropenem and in 1 of 86 patients (1%) receiving cefotaxime (95% confidence interval: -0.7%, 10.6%). None were thought to be drug related. Twenty-four meropenem-treated patients (24%) and 11 cefotaxime-treated patients (12%) had neurological abnormalities before therapy. In patients without pretherapy neurological abnormalities, these abnormalities were present after treatment in 4 of 74 meropenem-treated patients (5%) and in 2 of 81 cefotaxime-treated patients (2%) (95% confidence interval: -3.2%, 9.1%). Of 75 meropenem-treated and 64 cefotaxime-treated patients with pretherapy positive cerebrospinal-fluid cultures, 68 and 59, respectively, had repeat lumbar punctures. Bacterial eradication was found to be 100% in both groups. Our data suggest that meropenem may be a carbapenem agent that is well tolerated and effective in the treatment of bacterial meningitis.

Topics: Adolescent; Cefotaxime; Child; Child, Preschool; Dexamethasone; Female; Hearing Tests; Humans; Infant; Male; Meningitis, Bacterial; Meropenem; Nervous System Diseases; Prospective Studies; Seizures; Thienamycins; Treatment Outcome

Third-generation cephalosporins are presently the agents of choice for the empirical antimicrobial therapy of bacterial meningitis. However, a number of factors associated with these agents, namely the development of resistance by pneumococci, limited activity against some Enterobacteriaceae and Pseudomonas spp., and the possible adverse effects of their bacteriolytic mode of action, indicate that newer classes of antimicrobial agents be evaluated for the treatment of bacterial meningitis. Meropenem is a carbapenem antibiotic which is highly active against the major bacterial pathogens causing meningitis, and penetrates well into the cerebrospinal fluid. Two prospective randomised studies in 56 adult bacterial meningitis patients have compared meropenem 40 mg/kg 8-hourly, up to a maximum of 6 g/day (n = 28) with cephalosporin treatment, i.e. cefotaxime (n = 17) or ceftriaxone (n = 11). Patients were assessed by neurological examination, Glasgow Coma Score and Herson-Todd score. Clinical cure was observed in all 23 evaluable patients treated with meropenem (100%) and with 17 of the 22 evaluable cephalosporin-treated patients (77%). All pre-treatment isolates were eradicated except one isolate of Staphylococcus aureus in a cefotaxime-treated patient. Neurological sequelae were noted in three meropenem and four cephalosporin-treated patients. No patients in either treatment group experienced seizures after the start of therapy. This was despite the fact that a patient in each group had experienced seizures before therapy, several had underlying CNS disorders, and that doses of 6 g/day of meropenem were given. Hearing impairment was recorded in 11 meropenem and nine cephalosporin treated patients. Three patients in the meropenem group and one in the cephalosporin group died during treatment for reasons unrelated to study therapy. Overall, the results of this study indicate that meropenem is an effective and well-tolerated antibiotic for the treatment of bacterial meningitis in adults.

Topics: Adult; Carbapenems; Cefotaxime; Ceftriaxone; Humans; Meningitis, Bacterial; Meropenem; Thienamycins; Treatment Outcome

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Male; Meningitis, Bacterial; Meningitis, Viral; Meropenem; Thienamycins

Gram-negative bacillary meningitis remains a rare occurrence, even in patients with human immunodeficiency virus. Current literature only describes anecdotal cases of spontaneous nosocomial Proteus mirabilis meningitis. This report describes the clinical manifestations and management of a patient with healthcare-associated spontaneous Gram-negative bacillary meningitis in a patient with advanced human immunodeficiency virus disease.. A 23-year-old Congolese female was hospitalized in a human immunodeficiency virus specialized center for ongoing weight loss, chronic abdominal pain, and vomiting 9 months after initiation of treatment for tuberculosis meningitis. Hospitalization was complicated by healthcare-associated Gram-negative bacillary meningitis on day 18. Blood and cerebrospinal fluid cultures confirmed Proteus mirabilis. Antibiotic susceptibility testing showed extended spectrum beta-lactamase resistant to common antibiotics, and sensitive to meropenem. Despite initiation of high-dose meropenem by intravenous infusion (2 g every 8 hours), the patient did not improve, and died after 4 days of meropenem treatment. Gram-negative bacillary meningitis remains rare and is associated with an unfavorable prognosis.. This case report highlights the importance of microbiological identification of pathogens in resource-limited settings. As Gram-negative bacillary meningitis does not present with pleocytosis in patients with advanced human immunodeficiency virus, a negative lumbar puncture cannot exclude this diagnosis. Access to clinical bacteriology in resource-limited settings is essential to enable correct antibiotic treatment and avoid overuse of antibiotics to which there is already resistance. It further plays an essential role in public health by identifying antibiotic susceptibilities. Infection prevention and control measures must be reinforced in order to protect patients from such avoidable healthcare-associated infections.

Topics: Adult; Anti-Bacterial Agents; Cross Infection; Female; Gram-Negative Bacteria; HIV; HIV Infections; Humans; Meningitis; Meningitis, Bacterial; Meropenem; Proteus mirabilis; Young Adult

Campylobacter fetus is an uncommon Campylobacter species, and its infections mainly cause infective endocarditis, aortic aneurysm, and meningitis rather than enteritis. It is more likely to be detected in blood than Campylobacter jejuni or Campylobacter coli, specifically reported in 53% of patients. In our case, C. fetus was detected in both blood and cerebrospinal fluid (CSF) cultures.. A 33-year-old woman, who was on maintenance chemotherapy for acute lymphoblastic leukemia (ALL), presented to our clinic with chief complaints of severe headache and nausea. Blood and CSF cultures revealed C. fetus. We administrated meropenem 2 g intravenously (IV) every 8 h for 3 weeks, and she was discharged without neurological sequelae.. We encountered a case of C. fetus meningitis without gastrointestinal symptoms, neck stiffness or jolt accentuation in a patient with ALL. Undercooked beef was considered the source of C. fetus infection in this case, suggesting that the need for a neutropenic diet and safe food handling be considered.

Topics: Adult; Anti-Bacterial Agents; Campylobacter fetus; Campylobacter Infections; Ceftriaxone; Diagnosis, Differential; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Female; Foodborne Diseases; Humans; Meningitis, Bacterial; Meropenem; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome

Cefotaxime, alone or with ampicillin, is frequently used in empirical treatment of acute bacterial meningitis (ABM). Meropenem is a less extensively investigated alternative. The aim of the study was to investigate the effects of empirical treatment with meropenem compared to cefotaxime plus ampicillin on outcome in ABM. The study was based on data from the Swedish quality register for ABM collected between January 2008 and December 2016. Propensity score matching was performed to adjust for baseline differences between the groups. Mortality within 30 days was the primary outcome. The treatment regimens of interest were administered to 623 patients; 328 were given cefotaxime plus ampicillin whereas 295 received meropenem. Using propensity score matching, the 30-day mortality rates were 3.2% in the cefotaxime plus ampicillin group and 3.6% in the meropenem group. For matched cases, the odds ratio (OR) for 30-day mortality for meropenem versus cefotaxime plus ampicillin was 1.15 (confidence interval [CI], 0.41 to 3.22;

Topics: Adult; Age Factors; Aged; Ampicillin; Anti-Bacterial Agents; Cefotaxime; Drug Therapy, Combination; Female; Humans; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Propensity Score; Registries; Sweden; Treatment Outcome

Treatment of anthrax is challenging, especially during the advanced stages of the disease. Recently, the Centers for Disease Control and Prevention (CDC) updated its recommendations for postexposure prophylaxis and treatment of exposed populations (before and after symptom onset). These recommendations distinguished, for the first time, between systemic disease with and without meningitis, a common and serious complication of anthrax. The CDC considers all systemic cases meningeal unless positively proven otherwise. The treatment of patients suffering from systemic anthrax with suspected or confirmed meningitis includes the combination of three antibiotics, i.e., a fluoroquinolone (levofloxacin or ciprofloxacin), a β-lactam (meropenem or imipenem), and a protein synthesis inhibitor (linezolid or clindamycin). In addition, treatment with an antitoxin (anti-protective antigen antibodies) and dexamethasone should be applied. Since the efficacy of most of these treatments has not been demonstrated, especially in animal meningitis models, we developed an anthrax meningitis model in rabbits and tested several of these recommendations. We demonstrated that, in this model, ciprofloxacin, linezolid, and meropenem were ineffective as single treatments, while clindamycin was highly effective. Furthermore, combined treatments of ciprofloxacin and linezolid or ciprofloxacin and dexamethasone failed in treating rabbits with meningitis. We demonstrated that dexamethasone actually hindered blood-brain barrier penetration by antibiotics, reducing the effectiveness of antibiotic treatment of anthrax meningitis in this rabbit model.

Topics: Animals; Anthrax; Anti-Bacterial Agents; Antitoxins; Bacillus anthracis; Central Nervous System; Ciprofloxacin; Clindamycin; Dexamethasone; Disease Models, Animal; Drug Combinations; Imipenem; Levofloxacin; Linezolid; Meningitis, Bacterial; Meropenem; Rabbits; Treatment Failure

Purulent meningitis refers infection of the subarachnoid space by various purulent bacteria and the corresponding inflammation of the leptomeninges. However, purulent meningitis due to Rhodococcus equi is extremely rare.. A 40-year-old man presented with fever and intermittent headache for 6 days. Two hours prior to admission, he developed epileptic seizures.. Brain computed tomography and magnetic resonance imaging showed intracerebral malacic lesions. Bacterial culture of cerebrospinal fluid revealed the presence of R. equi. A diagnosis of purulent meningitis caused by R. equi was made.. The patient was treated with intravenous meropenem (1000 mg every 8 hours) for 19 days; then he was discharged and instructed to continue the intravenous meropenem for two weeks. After a follow-up period of 2 months, the patient had recovered completely.. After a follow-up period of 2 months, the patient had recovered completely.. Central nervous system infection caused by R. equi is rare. Early bacterial culture of CSF is important for timely diagnosis. With sufficient antibiotic therapy, the prognosis can be favorable.

Topics: Actinomycetales Infections; Adult; Anti-Bacterial Agents; Cerebrospinal Fluid; Humans; Male; Meningitis, Bacterial; Meropenem; Rhodococcus equi; Thienamycins

Klebsiella pneumonia (K. pneumonia), primarily a hospital-acquired pathogen, can cause a variety of deep-seated infections with significant morbidities. However, in the current scenario of global rise in antibiotic abuse, unexpected infection could be caused by K. pneumoniae.. A 56-year-old male who presented with intermittent headache and low fever was admitted, he had transsphenoidal surgery for pituitary adenoma 3 years ago. Routine laboratory tests revealed an elevated WBC count of 10.12 × 10/L and C-reactive protein (CRP) 12.9 mg/L. computed tomography (CT) revealed the sellar region with suspicious hemorrhage.. The patient was initially diagnosed with acute residual tumor hemorrhage. But the consequent diagnose of Klebsiella pneumoniae purulent meningitis was made based on the cerebrospinal fluid lab test and cerebrospinal fluid (CSF) and blood culture, and CT scan.. Lumbar puncture examination was made and the antibiotics were adjusted to meropenem and vancomycin according to the antibiotic sensitivity test. But because of the patient's unstable vital signs, his family refuse further lateral ventricular drainage.. The infection was out of control and the patient died of spontaneous breath and heartbeat arrest.. Through this case, we could learn that any clue of suspicious intracranial infection should be carefully considered in the current scenario of global rise in antibiotic abuse. The manifestation of intermittent headache and mild fever could be potential signs of fatal infection, and prompt appropriate measures should be taken timely.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Fatal Outcome; Fever; Headache; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Shock, Septic; Thienamycins; Vancomycin

Shunt infections are seen in 3% to 20% of patients who have cerebrospinal fluid (CSF) shunts. Although the staphylococcal species are the most common cause of shunt-related infections, Gram-negative bacteria are increasingly reported with higher mortality rates. Tigecycline, a glycylcycline, is not approved for children. But in the era of nosocomial infections due to multidrug-resistant pathogens, it can be the life-saving option. We report an infant with ventriculoperitoneal shunt-related meningitis treated with a tigecycline combination regimen. A 5-month-old boy who had a ventriculoperitoneal shunt was admitted with meningitis. Extended spectrum β-lactamase-producing Klebsiella pneumoniae grew in the CSF. At the end of the fourth week of intravenous meropenem plus gentamicin therapy, carbapenem-resistant K pneumoniae grew in the CSF (mean inhibitory concentration value for meropenem >4 μg/mL, by E-test). The infected shunt was removed, and an external ventricular drainage catheter was inserted. With permission, intravenous tigecycline (1.2 mg/kg per dose twice a day) and intrathecal amikacin were added to the meropenem. Intrathecal amikacin could be given for only 7 days. On the sixth day of tigecycline treatment, the CSF was sterilized. Antibiotic therapy was given and consisted of a total of 60 days of meropenem and 20 days of tigecycline therapy. Because no available efficacy and safety data from randomized-controlled studies exist, tigecycline must be used only as salvage therapy, in combination with other drugs, for critically ill children who have no alternative treatment options.

Topics: Amikacin; Drug Therapy, Combination; Humans; Hydrocephalus; Infant; Infant, Premature, Diseases; Infusions, Intravenous; Injections, Spinal; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Minocycline; Off-Label Use; Salvage Therapy; Thienamycins; Tigecycline; Ventriculoperitoneal Shunt

To examine the variables associated with mortality in patients with Acinetobacter baumannii-related central nervous system infections treated with intrathecal colistin.. This multi-centre retrospective case control study included patients from 11 centres in Turkey, as well as cases found during a literature review. Only patients with CNS infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii treated with intrathecal colistin were included in this study. The variables associated with mortality were determined by dividing the patients into groups who died or survived during hospitalisation, and who died or survived from Acinetobacter meningitis.. Among the 77 cases enrolled in the study, 35 were found through a literature review and 42 were cases from our centres. Forty-four cases (57.1%) were male and the median age was 48 years (range: 20-78 years). Thirty-seven patients (48%) died during hospitalisation. The variables associated with increased all-cause mortality during hospitalisation included old age (odds ratio, 1.035; 95% confidence interval (CI), 1.004-1.067; p=0.026) and failure to provide cerebrospinal fluid sterilisation (odds ratio, 0.264; 95% confidence interval, 0.097-0.724; p=0.01). There is a trend (P=0.062) towards higher mortality with using of meropenem during meningitis treatment. Fifteen cases (19%) died from meningitis. There were no significant predictors of meningitis-related mortality.. The mortality rate for central nervous system infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii is high. Old age and failure to provide CSF sterilisation are associated with increased mortality during hospitalisation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Case-Control Studies; Cerebral Ventriculitis; Colistin; Female; Humans; Injections, Spinal; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Outcome Assessment, Health Care; Retrospective Studies; Thienamycins; Young Adult

Caulobacter spp. are Gram-negative bacteria that have rarely been found to be pathogenic in humans.. This report describes the first case, to our knowledge, of meningitis in an adult patient caused by Caulobacter spp. A 75-year-old man was operated for a glioblastoma with no evident signs of primary infection in the wound site. Eight days after surgery, the patient developed signs and symptoms of meningitis. Caulobacter was then isolated on 3 separate occasions in the patient's cerebrospinal fluid. Thereafter, specific antibiotic therapy began. After 2 weeks of therapy, the patient was discharged with complete resolution of any related symptoms.. Caulobacter spp. can cause adult meningitis even where there is no evidence of surgical site infection.

Topics: Aged; Brain Neoplasms; Caulobacter; Cerebrospinal Fluid; Glioblastoma; Gram-Negative Bacterial Infections; Humans; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Postoperative Complications; Thienamycins; Virulence

A 13-year-old female experienced a recurrence of baclofen pump-related central nervous system (CNS) infection caused by Achromobacter, despite absence of retained foreign material. Due to the failure of meropenem (120 mg/kg/d in divided doses every 8 hours and infused over 30 minutes) in the initial infection, the dose was infused over 4 hours during the recurrence. Meropenem is an antibiotic for which efficacy is time dependent, and 4-hour versus 30-minute infusions have been shown to prolong the time the concentration of the antibiotic exceeds the minimum inhibitory concentration (MIC) of the organism at the site of infection (T>MIC). Meropenem serum concentrations were obtained and indicated that T>MIC was at least 75% of the dosing interval. Our patient improved with no noted recurrences or adverse effects on the extended-infusion meropenem regimen. Utilization of extended-infusion beta-lactam dosing whenever possible in the treatment of serious infections caused by gram-negative organisms should be considered, as this dosing appears to be safe and improves the probability of achieving pharmacokinetic/pharmacodynamic goals.

Topics: Achromobacter denitrificans; Adolescent; Anti-Bacterial Agents; Baclofen; Drug Administration Schedule; Female; Gram-Negative Bacterial Infections; Humans; Infusion Pumps, Implantable; Injections, Spinal; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Muscle Relaxants, Central; Recurrence; Thienamycins

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

Most post-neurosurgical meningitis research has been focused on large cohorts with numerous cases followed over several years. However, the characteristics of post-neurosurgical meningitis in an entire single year are still unclear, and knowledge of these characteristics might influence the selection of appropriate antibiotics and therapeutic strategies for the successful management of this disease. Our aim is to obtain a better understanding of post-neurosurgical meningitis over a single entire year.. Patients with positive meningitis cultures after neurosurgical operations in our hospital during the entire year of 2012 were included in the analysis. We report demographic characteristics, morbidity during different seasons, clinical and bacteriological profiles, sensitivity to antibiotics and causes of the post-neurosurgical meningitis infections in our cohort.. Of the 6407 patients who underwent neurosurgical procedures during the study period, 146 developed post-neurosurgical meningitis and the overall incidence of meningitis was 2.28%. The incidence of meningitis was significantly higher in patients who underwent surgery in the autumn and winter than spring or summer (p=0.000). The most common organisms causing meningitis were Gram-positive bacteria, followed by the Klebsiella and Baumannii species. Compound sulfamethoxazole (52.6%) and vancomycin (10.5%) were the most active antibiotics against Gram-positive bacteria strains, whereas meropenem (43.8%) and polymyxin (18.8%) were active against Gram-negative bacillus strains.. Post-neurosurgical meningitis usually occurs in the autumn and winter of the year in our hospital. Gram-positive organisms, which are sensitive to compound sulfamethoxazole and vancomycin, are the most common causative pathogens of post-neurosurgical meningitis in the northern mainland of China.

Topics: Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; Child; Child, Preschool; China; Drug Resistance, Bacterial; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Neurosurgical Procedures; Polymyxins; Postoperative Complications; Pseudomonas Infections; Retrospective Studies; Seasons; Staphylococcal Infections; Sulfamethoxazole; Thienamycins; Vancomycin; Young Adult

We present a 64-year-old man who was treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemoimmunotherapy for mantle cell lymphoma and developed purulent meningitis, probably caused by Leuconostoc sp. The patient had severe hypogammaglobulinemia, which is a possible complication of rituximab therapy. To our knowledge and after reviewing the available medical literature, this is the first described case of purulent meningitis caused by Leuconostoc sp. in a patient with mantle cell lymphoma that appeared after treatment with the R-CHOP protocol. The diagnosis of purulent meningitis was based on clinical, laboratory and cytological cerebrospinal fluid findings, in addition to blood culture results in which we isolated Leuconostoc sp. The patient was treated with meropenem with full recovery.. Burada mantle hücreli lenfoma tanısı ile R-CHOP (rituksimab, siklofosfamid, doksorubisin, vinkristin, prednizolon) kemoimmünoterapisi ile tedavi edilen ve muhtemelen Leuconostoc cinsi etkene bağlı pürülan menenjit gelişen 64 yaşında bir erkek hastayı sunuyoruz. Hastanın rituksimab tedavisinin olası komplikasyonlarından biri olan ağır hipogammaglobulinemisi bulunmakta olup, bildiğimiz kadarı ile ve mevcut tıbbi literatürün taranması sonrasında, olgumuz R-CHOP protokolü ile tedavi sonrası Leuconostoc cinsi etkene bağlı pürülan menejit gelişen mantle hücreli lenfoma tanılı ilk hastadır. Pürülan menenjit tanısı klinik bulgular, laboratuvar ve beyin-omurilik sıvısının sitolojik bulguları ve Leuconostoc izole ettiğimiz kan kültürünü temel alıyordu. Hasta meropenem tedavisi ile tamamen iyileşti.

Topics: Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Multiple, Bacterial; Gram-Positive Bacterial Infections; Humans; Leuconostoc; Lymphoma, Mantle-Cell; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Opportunistic Infections; Rituximab; Thienamycins

Pantoea calida, a recently described environmental Enterobacteriaceae organism, has not yet been associated with human infection.. We report a case of postoperative meningitis caused by P. calida. After pituitary adenoma resection, a 52-year-old Caucasian woman developed febrile meningitis confirmed by cerebrospinal fluid analysis. P. calida was grown in pure culture from this fluid and was firmly identified with partial rpoB gene sequencing. She was cured by a 14-day course of meropenem.. P. calida must be added to the list of opportunistic Enterobacteriaceae pathogens responsible for postsurgical meningitis. It is easily identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Topics: Adenoma; Anti-Bacterial Agents; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Meningitis, Bacterial; Meropenem; Middle Aged; Pituitary Neoplasms; Thienamycins

Pseudomonas aeruginosa meningitis is an uncommon complication of neurosurgical procedures or head trauma. Here, a case of infectious mid basilar artery aneurysm from Pseudomonas meningitis, and its angiographic remission from timely antibiotic therapy, is reported.

Topics: Adult; Angiography, Digital Subtraction; Anti-Bacterial Agents; Carotid Artery, Internal, Dissection; Cerebral Angiography; Female; Humans; Image Processing, Computer-Assisted; Intracranial Aneurysm; Meningitis, Bacterial; Meropenem; Ofloxacin; Ophthalmic Artery; Pseudomonas Infections; Thienamycins

A 48-year-old man with a history of a penetrating brain injury was referred with a presumptive diagnosis of bacterial meningitis. Examination revealed a brain abscess in addition to meningitis. Blood and cerebrospinal fluid (CSF) cultures were negative for bacteria, and empirical IV antibiotic therapy with vancomycin (VCM) and meropenem was initiated. Despite initial improvement, however, his condition rapidly deteriorated into coma following intraventricular rupture of the abscess and hydrocephalus. Thereafter, an emergency ventriculostomy was performed and the abscess was evacuated. Bacterial cultures of the pus were negative. To manage the hydrocephalus, 150-200 ml of CSF were drained daily. Intraventricular administration of VCM (20 mg q.d.) was added to the IV antibiotic therapeutic regimen after surgery. Although the primary abscess rapidly decreased in size, ependymitis developed in the fourth ventricle. This new lesion, which resulted from CSF dissemination from the primary abscess, was refractory to treatment, and eventually disappeared after the intraventricular VCM dosage was increased from 20 to 30 mg and continued for 30 days. A possible reason for the development of fulminant ependymitis and why it was refractory to treatment despite the shrinkage of the primary lesion may be that physiological CSF flow from the lateral to the fourth ventricle was lost due to CSF drainage, and the stagnant CSF flow coupled with an insufficient VCM level in the fourth ventricle facilitated the rapid growth of pathogens. Although intraventricular antibiotic administration is efficacious for treating ruptured brain abscesses, it may be associated with the unexpected development of secondary lesions.

Topics: Anti-Bacterial Agents; Brain Abscess; Cerebrospinal Fluid Shunts; Ependyma; Humans; Hydrocephalus; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Rupture, Spontaneous; Thienamycins; Vancomycin

Gram-negative bacillary (GNB) ventriculitis and meningitis are rare but serious complications after neurosurgery. Prospective studies on antibiotic treatment for these infections are lacking, and retrospective reports are sparse. At our hospital in Uppsala, Sweden, meropenem has been recommended as empirical therapy since 1996, with the addition of intraventricular gentamicin in cases that do not respond satisfactorily to treatment. In this study, we retrospectively compare the efficacy of combination treatment with intraventricular gentamicin to that of systemic antibiotics alone. In addition, we report our experience of meropenem for the treatment of GNB ventriculomeningitis.. Adult consecutive patients with gram-negative bacteria isolated from cerebrospinal fluid during a 10-year period and with postneurosurgical GNB ventriculitis or meningitis were included retrospectively. Data were abstracted from the medical records.. Thirty-one patients with neurosurgical GNB ventriculitis or meningitis and follow-up for 3 months were identified. The main intravenous therapies were meropenem (n = 24), cefotaxime (n = 3), ceftazidime (n = 2), imipenem (n = 1), and trimethoprim-sulfamethoxazole (n = 1). Thirteen patients were given combination treatment with appropriate intraventricular gentamicin. These patients had a higher cure rate and a lower relapse rate than did those treated with intravenous antibiotics alone (P = .03). Relapse occurred in 0 of 13 patients treated intraventricularly and in 6 of 18 patients treated with systemic antibiotics alone. The mortality rate was 19%; 3 patients in each group died, but in no case was death considered to be attributable to meningitis.. Our results support combination treatment with intraventricular gentamicin for postneurosurgical GNB ventriculomeningitis. Meropenem seems to be an effective and safe alternative for the systemic antibiotic treatment of these neurointensive care infections.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Cerebral Ventriculitis; Cerebrospinal Fluid; Drug Therapy, Combination; Gentamicins; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infusions, Intraventricular; Meningitis, Bacterial; Meropenem; Middle Aged; Retrospective Studies; Surgical Wound Infection; Sweden; Thienamycins; Treatment Outcome; Young Adult

An evaluation committee studied the relationship between initial treatment drug and prognosis in 339 of 466 subjects with bacterial meningitis treated at 108 institutions between April 2004 and January 2007, after excluding those with uncertain diagnosis or non-assessable records. Prognosis was considered unfavorable if meningitis sequelae such as quadriplegia, deafness, or epilepsy were present in 3- month follow-up; Based on this definition, 43 (12.7%) had a poor prognosis. No significant relationship was seen between unfavorable prognosis and age or causative pathogen. More had an unfavorable prognosis if treatment was initiated 4 days or later after onset. The percentage with an unfavorable prognosis was 6.4% (4/64) in the group administered combined panipenem/betamipron (PAPM/BP) plus ceftriaxone (CTRX), 10.5% (6/57) administered MEPM plus cefotaxime (CTX), 14.0% (7/50) administered meropenem (MEPM) plus CTRX, and none of the 23 administered CTRX alone. The percentage with an unfavorable prognosis was 26.2% (11/42) in those administered MEPM, significantly higher than that in those administered PAPM/BP plus CTRX, MEPM plus CTX, or CTRX alone (p < 0.05). We concluded that in initial treatment, it would be more desirable to use MEPM combined with another drug than alone.

Topics: Anti-Bacterial Agents; beta-Alanine; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Drug Therapy, Combination; Humans; Infant; Meningitis, Bacterial; Meropenem; Prognosis; Thienamycins

We reported a case of meningitis caused by group B Streptococcus treated with high dose of meropenem (MEPM). A 67-year-old male was suffering from lumbago, fever up, vomiting and convulsion. He had received tumor resection of spinal cord at 40 years old. At the first consultation to our hospital, he had felt strong neck stiffness with Glasgow Coma Scale 5 (El, V1, M3), and his body temperature was 37.0 degrees C. His laboratory findings were as follows; white blood cell count 14600/microL, C-reactive protein 4.39mg/dL, and marked elevation of the cell count in the cerebrospinal fluid. We had administered high dose of meropenem, 6 g/day, and also vancomycin (VCM) on therapeutic drug monitoring. Since his clinical symptoms and laboratory findings had not shown adequate response after 4 days later, we had changed VCM to linezolid 1200 mg/day, and had also continued MEPM, which had resulted in prompt resolution of the clinical symptoms and laboratory findings. Microbiological examination for cerebrospinal fluid has yielded a growth of serotype III group B Streptococcus (Streptococcus agalactiae). Since there have been few data on 6 g/day MEPM against meningitis in spite of recommendation in several guidelines, further studies would be necessary including pharmacokinetic-pharmacodynamic analysis.

Topics: Acetamides; Aged; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Linezolid; Male; Meningitis, Bacterial; Meropenem; Oxazolidinones; Pulse Therapy, Drug; Serotyping; Streptococcal Infections; Streptococcus agalactiae; Thienamycins; Treatment Outcome; Vancomycin

In this report, we present a case of postneurosurgical meningitis due to Providencia stuartii, which was treated successfully with meropenem therapy lasting 21 days.

Topics: Adult; Anti-Bacterial Agents; Enterobacteriaceae Infections; Humans; Male; Meningitis, Bacterial; Meropenem; Postoperative Complications; Providencia; Thienamycins; Treatment Outcome

The cerebrospinal fluid (CSF) inhibitory titer (CSF-IT) of an antibiotic, which can be used to estimate the duration of time above the agent's MIC in the CSF, was introduced as one of the indices to evaluate the effectiveness of antibiotic selection in treating bacterial meningitis. The CSF-IT was determined via a microdilution method. A suspension of the causative organism was added to a tube containing twofold diluted CSF and double-concentrated Mueller-Hinton broth with supplement. The CSF-IT was determined by the maximum point without turbidity of medium after overnight incubation at 37 degrees C. Concerning the strain of beta-lactamase-negative ampicillin-resistant Haemophilus influenzae (BLNAR), the killing rates of both meropenem and piperacillin were compared in an in vitro pharmacokinetic (PK) model, in which human pharmacokinetics in CSF were simulated. Organisms recovered from the CSF in 37 treated clinical cases of bacterial meningitis were H. influenzae, Streptococcus agalactiae, Streptococcus pneumoniae, Escherichia coli, and Neisseria meningitidis; in these cases, the CSF-IT ranged from 1: 8 to as high as 1: 4 096. In the in vitro PK model, the concentrations of both drugs were higher than the MICs over a period of 24 h; however, the killing rate of piperacillin was higher than that of meropenem, and bacterial regrowth was observed after the administration of meropenem. A CSF-IT value higher than 1: 32 indicates that the antibiotic concentration in the CSF exceeds the MIC for 24 h. The effect of piperacillin on BLNAR depends not only on the time above MIC of 24 h but also on the maximum concentration in the CSF.

Topics: Adult; Anti-Bacterial Agents; Child; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Infant, Newborn; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Piperacillin; Thienamycins

Topics: Anti-Bacterial Agents; Bacteria; Cerebrospinal Fluid; Humans; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Thienamycins

Meropenem (MEM; 2 g/8 hr; minimum inhibitory concentration [MIC] = 256 mg/L) plus sulbactam (SUL; 1 g/8 hr; MIC = 128 mg/L) (two-drug-therapy period), and subsequent additional intravenous colistin (COL; 2.5 mg/kg/12 hr) and intraventricular (COL, 5 mg/day; MIC = 1 mg/L) (three-drug-therapy period) were sequentially used in a patient with postneurosurgery bacteremic meningitis due to a multidrug-resistant Acinetobacter baumannii (MDRAB) isolate (AB(1)). We detected 4- to 32-fold increases in peak or trough cerebrospinal fluid bactericidal titer and serum bactericidal titer in three-drug-therapy period when comparing to those in two-drug-therapy period. The time-kill study with MEM, SUL, and COL alone or varied combinations (all at 1 x MIC) against AB(1) and another genetically nonrelated MDRAB isolate (AB(134) [MICs of MEM = 64 mg/L, SUL = 16 mg/L, and COL = 1 mg/L]) was performed. The two-drug combinations (MEM + SUL, MEM + COL, and SUL + COL) each elicited different inhibitory effect on AB(1) and AB(134) at 6 hr. Bacterial regrowth at 24 hr was observed in the experiments in which the MDRAB isolate was inhibited earlier by COL alone (AB(1) and AB(134)), by MEM plus SUL (AB(1)), and by MEM plus COL (AB(134)), but not in SUL plus COL, and MEM + SUL + COL. Combined use of COL with MEM and/or SUL may provide good therapeutic options, even though MEM and SUL are in vitro resistance to the MDRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Neurosurgical Procedures; Postoperative Complications; Sulbactam; Thienamycins; Time Factors

Opportunistic infections contribute to morbidity and mortality of patients undergoing hematopoietic stem cell transplantation and treatment for malignancies. Rothia mucilaginosa, a gram-positive bacterium, is responsible for rare, but often fatal meningitis in severely immunocompromised patients. We describe two cases of meningitis from discrete strains of R. mucilaginosa on our pediatric bone marrow transplant unit, summarize the published cases of R. mucilaginosa meningitis in oncology and stem cell transplant patients, and provide updated recommendations regarding the use of antibiotic therapy in this patient population.

Topics: Actinomycetales Infections; Adolescent; Anti-Bacterial Agents; Ceftazidime; Cerebrospinal Fluid Shunts; Child; Cord Blood Stem Cell Transplantation; Drug Therapy, Combination; Fatal Outcome; Female; Humans; Immunocompromised Host; Leukemia, Megakaryoblastic, Acute; Male; Meningitis, Bacterial; Meropenem; Micrococcaceae; Opportunistic Infections; Postoperative Complications; Rifampin; Sepsis; Thienamycins; 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

Acinetobacter baumannii is a prolific nosocomial pathogen renowned for its multidrug-resistant nature. We report a case of community-acquired meningitis due to A. baumannii. The case highlights the potential pathogenicity of this organism and raises concerns that this highly adaptable organism may soon evolve into a significant community pathogen, too.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Anti-Inflammatory Agents; Ceftriaxone; Community-Acquired Infections; Cross Infection; Dexamethasone; Humans; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Thienamycins

Acinetobacter baumannii is a major cause of nosocomial infections in many hospitals and appears to have a propensity for developing multiple antimicrobial resistance rapidly.. We report two cases with post-surgical meningitis due to multidrug resistant A. baumannii which were successfully treated with high-dose intravenous meropenem therapy.. Multidrug resistant Acinetobacter spp. in intensive care units are a growing concern. High-dose meropenem is used in the treatment of these infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Middle Aged; Thienamycins

Topics: Acinetobacter baumannii; Adolescent; Adult; Aged; Amikacin; Anti-Bacterial Agents; Carbapenems; Cefepime; Cefoperazone; Cephalosporins; Ciprofloxacin; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Thienamycins; Turkey

To describe the use of and cerebral spinal fluid (CSF) penetration of a prolonged infusion meropenem regimen in a patient with Serratia marcescens meningitis.. A 54-year-old female was diagnosed with S. marcescens meningitis associated with an epidural abscess 57 days after surgery for a herniated spinal disk. Meropenem 2000 mg every 8 hours was administered as a prolonged (3 h) infusion for the purpose of optimizing pharmacodynamic exposure. Meropenem concentrations were measured from the patient's blood and CSF (via a lumbar drain). The prolonged infusion regimen resulted in concentrations in both serum and CSF above the meropenem minimum inhibitory concentration (MIC) of 0.047 microg/mL for 100% of the dosing interval. After 6 days of therapy, the patient showed no further signs of infection and was subsequently discharged to a rehabilitation facility. At follow-up, she had completed a 4 week course of the prolonged infused therapy without relapse or adverse events.. Gram-negative infections of the central nervous system result in high morbidity and mortality. These infections are often difficult to treat because of poor antibiotic penetration coupled with increasing antibiotic resistance. Although there are 2 other case reports that describe the use of prolonged infusion of meropenem, our patient had a lumbar drain in place, thereby allowing us to collect multiple CSF samples and more accurately assess meropenem exposure at the site of infection. CSF penetration was 6.4% in this patient, resulting in 100% time above the MIC throughout the dosing interval.. In this patient with meropenem-susceptible S. marcescens meningitis, the use of a high-dose prolonged infusion of meropenem resulted in adequate exposure at the site of infection and a successful clinical response.

Topics: Anti-Bacterial Agents; Drug Administration Schedule; Female; Humans; Meningitis, Bacterial; Meropenem; Middle Aged; Serratia Infections; Serratia marcescens; Thienamycins

Risk factors, therapy and outcome of 15 cases of nosocomial meningitis due to Pseudomonas aeruginosa is reviewed. No difference in risk factors was found, however mortality for Ps. aeruginosa was significantly higher (33.3 vs 15.1% p<0.04).

Topics: Adolescent; Anti-Bacterial Agents; Cefotaxime; Ceftazidime; Chi-Square Distribution; Child, Preschool; Chloramphenicol; Cross Infection; Drug Therapy, Combination; Female; Gentamicins; Humans; Infant; Infant, Newborn; Male; Meningitis, Bacterial; Meropenem; Pseudomonas Infections; Retrospective Studies; Risk Factors; Survival Analysis; Thienamycins

A high-performance micellar electrokinetic capillary chromatography (MEKC) has been demonstrated for the determination of meropenem in human plasma and in cerebrospinal fluid (CSF) and application in meningitis patients after intravenous (IV) administration. Plasma sample was pretreated by means of solid-phase extraction (SPE) on C(18) cartridge and CSF sample was by direct injection without sample pretreatment, with subsequent quantitation by MEKC. The separation of meropenem was carried out in an untreated fused-silica capillary (40.2 cm x 50 microm I.D., effective length 30 cm) and was performed at 25 degrees C using a background electrolyte consisting of Tris buffer (40 mM, pH 8.0) solution with sodium dodecyl sulfate (SDS) as the running buffer and on-column detection at 300 nm. Several parameters affecting the separation and sensitivity of the drug were studied, including pH, the concentrations of Tris buffer and surfactant. Using cefotaxime as an internal standard (IS), the linear ranges of the method for the determination of meropenem in plasma and in CSF were all over 0.5-50 microg/mL; the detection limits (signal-to-noise ratio=3) of meropenem in plasma and in CSF were 0.2 microg/mL and 0.3 microg/mL, respectively.

Topics: Adult; Anti-Bacterial Agents; Chromatography, Micellar Electrokinetic Capillary; Humans; Meningitis, Bacterial; Meropenem; Reproducibility of Results; Thienamycins

Shewanella putrefaciens is a facultatively anaerobic, non-motile, Gram-negative, non-fermentative bacterium. It is found in various environments and has been isolated worldwide. S. putrefaciens is a rare cause of brain abscesses and meningitis. This is a case report of a cerebellar abscess and meningitis caused by Shewanella putrefaciens and Klebsiella pneumoniae in a river trap fisherman.

Topics: Adult; Brain Abscess; Cerebellar Diseases; Gram-Negative Bacterial Infections; Head; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis, Bacterial; Meropenem; Otitis Media; Radiography; Shewanella putrefaciens; 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

A 43-year-old man with no past history of underlying disease was admitted to an affiliated hospital, complaining of high fever and severe headache. Polynuclear dominant pleocytosis in the cerebrospinal fluid (CSF) suggested bacterial meningitis. He was immediately treated with several antibiotics, then his clinical symptoms improved, although intractable headache relapsed after withdrawal of the initial therapy. Thereafter he consulted our hospital for a second opinion. CSF examination in our hospital demonstrated mononuclear dominant pleocytosis with normal sugar value. However, bacterial culture of the CSF specimen yielded a gram-negative bacillus that was finally identified as a Campylobacter fetus on Skirrow's culture. Treatment with meropenem and other antibiotics improved both the clinical symptoms and CSF findings. Thus, meningitis with a Campylobacter fetus could manifest a chronic and atypical clinical course, careful attention should be paid to establish an early diagnosis.

Topics: Adult; Anti-Bacterial Agents; Campylobacter fetus; Campylobacter Infections; Chronic Disease; Humans; Male; Meningitis, Bacterial; Meropenem; Thienamycins

Enterococcal meningitis is an uncommon disease usually caused by Enterococcus faecalis and Enterococcus faecium and is associated with a high mortality rate. Enterococcus casseliflavus has been implicated in a wide variety of infections in humans, but never in meningitis.. A 77-year-old Italian female presented for evaluation of fever, stupor, diarrhea and vomiting of 3 days duration. There was no history of head injury nor of previous surgical procedures. She had been suffering from rheumatoid arthritis for 30 years, for which she was being treated with steroids and methotrexate. On admission, she was febrile, alert but not oriented to time and place. Her neck was stiff, and she had a positive Kernig's sign. The patient's cerebrospinal fluid was opalescent with a glucose concentration of 14 mg/dl, a protein level of 472 mg/dl, and a white cell count of 200/muL with 95% polymorphonuclear leukocytes and 5% lymphocytes. Gram staining of CSF revealed no organisms, culture yielded E. casseliflavus. The patient was successfully treated with meropenem and ampicillin-sulbactam.. E. casseliflavus can be inserted among the etiologic agents of meningitis. Awareness of infection of central nervous system with Enterococcus species that possess an intrinsic vancomycin resistance should be increased.

Topics: Aged; Ampicillin; Anti-Bacterial Agents; Cerebrospinal Fluid; Enterococcus; Female; Gram-Positive Bacterial Infections; Humans; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Sigmoid Diseases; Sulbactam; Thienamycins

Topics: Acinetobacter; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Cerebrospinal Fluid; Drug Therapy, Combination; Female; Humans; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Rifampin; Subarachnoid Hemorrhage; Thienamycins; Ventriculostomy

Topics: Brain Abscess; Drug Administration Schedule; Drug Resistance, Bacterial; Escherichia coli Infections; Humans; Infant, Newborn; Klebsiella Infections; Meningitis, Bacterial; Meropenem; Sepsis; Thienamycins; Treatment Outcome

To report a case of gram-negative bacillary meningitis (GNBM) secondary to multidrug-resistant Pseudomonas aeruginosa that was treated with intravenous meropenem and intrathecal and intravenous amikacin.. A 76-year-old Arabic woman with previous placement of an extraventricular device developed meningitis secondary to P. aeruginosa as a result of a previous pneumonia. The patient was treated with intravenous meropenem and amikacin, with the addition of intrathecal amikacin, until cerebrospinal cultures remained negative for 18 days. She did not experience any adverse effects as a result of the administration of the intrathecal amikacin. Although the meningitis subsequently resolved, the patient eventually died due to Candida glabrata fungemia.. Dual therapy is recommended for patients with P. aeruginosa meningitis. In our patient, the increasing resistance to imipenem and resistance to all other potential antibiotics resulted in the use of an alternative administration technique that has not been well documented in recent literature.. In patients who have GNBM due to P. aeruginosa, the combination of intrathecal and intravenous amikacin may be an option for therapy, especially when clinical options are limited by resistance, severity of illness, and location of the infection. More information is required and further study is needed on this topic.

Topics: Aged; Amikacin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Injections, Spinal; Meningitis, Bacterial; Meropenem; Pseudomonas aeruginosa; Thienamycins

The treatment of gram-negative infection of the central nervous system (CNS) presents a clinical challenge due to antibiotic resistance and difficulties with penetration into the cerebrospinal fluid (CSF). Two patients with gram-negative CNS infections were treated successfully with high-dose, prolonged infusions of meropenem. The CSF meropenem concentrations exceeded the minimum inhibitory concentration of the pathogen for virtually the entire dosing interval in both cases. Our experience demonstrates that dosage modification to maximize pharmacodynamic targets and bactericidal activity may be practically applied to optimize antibiotic treatment for difficult-to-treat CNS infections.

Topics: Adult; Cross Infection; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Pseudomonas aeruginosa; Serratia marcescens; Thienamycins; Time Factors

Pseudomonas stutzeri is a saprophytic microorganism that rarely causes severe infections. In this report, a 28 days old male patient with meningomyelocele at birth was presented. The patient was admitted to the hospital with fever, and diagnosed as meningitis on the basis of physical examination and leukocytosis (blood: 16.380/mm3, cerebrospinal fluid (CSF): 130/mm3; 90% PMNL). Following diagnosis ceftriaxone therapy was started led to improvement in clinical and laboratory findings. However on the 20th day, the clinical signs and symptoms became worse, and the patient was diagnosed to develop a second meningitis attack by laboratory examination of CSF. P. stutzeri was isolated from the CSF culture, and the isolate was found to be resistant to ceftriaxone. Upon this result the therapy has changed to meropenem. On the 5th day of the therapy, the patient has slightly improved and he was discharged due to the wishes of his parents, however he died two days after discharge. This first case of P. stutzeri meningitis in neonates was presented to withdraw attention to this clinical entity.

Topics: Anti-Bacterial Agents; Ceftriaxone; Cerebrospinal Fluid; Drug Resistance, Bacterial; Fatal Outcome; Humans; Infant, Newborn; Male; Meningitis, Bacterial; Meningomyelocele; Meropenem; Pseudomonas Infections; Pseudomonas stutzeri; Recurrence; Thienamycins; Treatment Failure

Comamonas testosteroni, a lesser-known member of the genus, has shown little apparent capacity for causing infections in humans. We here present a case of purulent meningitis due to C. testosteroni, which occurred in a patient who had recurrent cholesteatoma. Ceftriaxone treatment was not effective in this patient even though in vitro the bacteria were susceptible to the drug. The patient responded well to meropenem therapy.

Topics: Anti-Bacterial Agents; Cefotaxime; Cholesteatoma; Comamonas testosteroni; Gram-Negative Bacterial Infections; Humans; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Thienamycins

Epidemiological and microbiological studies were carried out using 575 strains of Haemophilus influenzae isolated from clinical specimens at Kitakyushu municipal medical center from January 1996 through December 1999. The strains isolated multiply were excluded. The strains of H. influenzae did not increase for 4 years, and were detected more in summer season, peaked in July, and less in winter season. Like the cases of Streptococcus pneumoniae, most (91.8%) of the strains was detected in the specimens from the respiratory tract, and also they were isolated mainly from infants under 4-years old (25.6%) and adults over 65-years old (24.2%) MICs of 7 antimicrobial agents, such as ampicillin (ABPC), sulbactam/ABPC, cefaclor, imipenem, panipenem, meropenem (MEPM), and levofloxacin (LVFX) were determined using broth microdilution methods. Among 575 strains of H. influenzae isolated from clinical specimens, 51 ABPC-resistant strains (8.9%) produced beta-lactamase, and 67 strains (11.6%) were beta-lactamase negative ampicillin resistant H. influenzae. The ABPC-resistant strains existed in 20.5%. Both of MEPM and LVFX showed excellent antimicrobial activity against H. influenzae including ABPC-resistant strains. Four cases of meningitis were reviewed. All of H. influenzae isolated possessed type b capsular antigen. All patients recovered by appropriate antimicrobial treatment. But one adult patient developed serious sequela.

Topics: Adult; Aged; Ampicillin; Anti-Infective Agents; beta-Lactamases; Cefaclor; Cephalosporins; Child, Preschool; Female; Haemophilus influenzae; Humans; Imipenem; Infant; Infant, Newborn; Levofloxacin; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Middle Aged; Ofloxacin; Respiratory System; Seasons; Sulbactam; Thienamycins

Topics: Aged; Anesthesia, Spinal; Drug Administration Schedule; Drug Resistance, Microbial; Humans; Male; Meningitis, Bacterial; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Recurrence; Thienamycins

Topics: Animals; Carbapenems; Central Nervous System; Haemophilus influenzae; Humans; Meningitis, Bacterial; Meropenem; Neurotoxicity Syndromes; Randomized Controlled Trials as Topic; Seizures; Thienamycins

Topics: Adult; Anti-Infective Agents; Anti-Inflammatory Agents; Brain Abscess; Humans; Magnetic Resonance Imaging; Male; Meningitis, Bacterial; Meropenem; Neutrophils; Nocardia Infections; Sarcoidosis, Pulmonary; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination

Meningitis caused by Campylobacter jejuni is rare, we describe a case following neurosurgery for intra-cranial haematoma in a chronic alcoholic patient. Conventional culture of CSF and blood was supplemented by polymerase chain reaction (PCR) detection of Campylobacter jejuni.

Topics: Adult; Alcoholism; Brain; Campylobacter Infections; Campylobacter jejuni; Humans; Male; Meningitis, Bacterial; Meropenem; Polymerase Chain Reaction; Thienamycins

Topics: Aged; Blood-Brain Barrier; Cefepime; Cefotaxime; Cephalosporins; Cerebrospinal Fluid; Cerebrospinal Fluid Shunts; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Hydrocephalus; Male; Meningitis, Bacterial; Meropenem; Postoperative Complications; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins

A case is reported of a patient who developed Acinetobacter meningitis after an external ventricular drainage system had been fitted for control of intracranial pressure. During the process, nine strains of Acinetobacter isolated from her cerebrospinal fluid were indistinguishable by analysis of total genomic DNA by pulse-field gel electrophoresis. The first eight strains were sensitive to meropenem and imipenem (MICs < 1 g/l). The MIC of the last one, which had been recovered after 32 days during two courses of treatment with meropenem, increased to > 32 g/l for meropenem, while with imipenem the increase was minimal (MIC = 1.5 g/l). The microorganism persisted in the central nervous system despite the administration of different antimicrobials, including intraventricular aminoglycosides and six changes in the external ventricular system. The patient died 68 days after admission to the intensive care unit from bilateral cerebral ischemic lesions, intraventricular hemorrhage and cerebral edema with endocraneal hypertension, the Acinetobacter ventriculitis also contributing to this state.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Cerebrospinal Fluid; Drug Resistance, Microbial; Female; Humans; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Thienamycins

The choice of an antibiotic for the treatment of a serious paediatric infection is generally a difficult problem. The arrival of Carbapenem resulted an important advance in the field of medicine due to its broad-spectrum, low incidence of resistances and good safety profile. Among Carbapenems, Meropenem introduction represents a progress because of its pharmacokinetics characteristics and blood-brain barrier penetration. Meropenem dosage depends on the patient weight, and the way of administration is potentially easier. Meropenem has been compared with the most used paediatric antimicrobial in controlled and randomised clinical trials, showing a high efficacy in the treatment of several infections (respiratory, urinary, intraabdominal, dermatological, septicemia) and in neutropenic and cystic fibrosis patients aged between one month and twelve years old. Meropenem is specially useful in the bacterial meningitis treatment because it penetrates into the cerebrospinal fluid of patients with inflamed meninges and reaches therapeutic concentrations, and because appearance of seizures is low. Adverse reactions produced by Meropenem show a poor incidence and its severity is usually mild. With regard to this characteristics, it can be concluded that Meropenem is an antimicrobial which efficacy and safety profiles guarantee its use in the treatment of severe paediatric infections.

Topics: Bacterial Infections; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Infant, Premature; Meningitis, Bacterial; Meropenem; Neutropenia; Respiratory Tract Infections; Thienamycins; Urinary Tract Infections

Meropenem is a new carbapenem antibiotic of with an antibacterian spectrum similar to that of imipenem, but from which it may mainly be differentiated by the possibility of its administration at high doses and it has no demonstrated proconvulsive effect, properties which make it applicable in the treatment of bacterial meningitis. The clinical and experimental experience in the treatment of bacterial meningitis with this antibiotic is herein reviewed. It has been observed that the efficacy and safety of meropenem in meningitis caused by N. meningitidis, H. influenzae and pneumococci sensitive to penicillin may be similar to that of cefotaxime or ceftriaxone in both the pediatric and adult population. There are very few reports on the treatment of meningitis caused by pneumococci resistant to penicillin. However, given that the activity of meropenem on these pneumococci is similar to that of cefotaxime and that the doses administered are much lower, it does not appear to be recommendable in the treatment of this indication, although it should be tested in all meningeal strain to these characteristics isolated. It may currently be considered that the main indication of meropenem in the infections of the central nervous system is in nosocomial meningitis by multiresistant gram negative bacilli such as those of the Klebsiella-Serratia-Enterobacter and Acinetobacter sp. group. Therefore a limited, albeit favorable, report on the clinical experience with meropenem is herein presented. Meropenem may also be useful in the treatment of meningitis by Pseudomonas aeruginosa in which other treatments have failed.

Topics: Adult; Animals; Blood-Brain Barrier; Child; Cross Infection; Disease Models, Animal; Humans; Meningitis, Bacterial; Meropenem; Rabbits; Thienamycins

In order to evaluate the antimicrobial activity of meropenem (MEPM), minimum inhibitory concentrations (MICs) of MEPM and control drugs were determined against clinical isolates from blood and cerebrospinal fluid that were obtained from January, 1993 to December, 1994. The results are summarized as follows; 1. The MIC-range, 50% MIC (MIC50) and 90% MIC (MIC90) of MEPM were equal to those of imipenem (IPM) and panipenem (PAPM) against Streptococcus pneumoniae including benzylpenicillin (PCG)-insensitive or -resistant S. pneumoniae, Streptococcus agalactiae and Listeria monocytogenes which are Gram-positive strains, and were stronger than those of ampicillin (ABPC) and cefotaxime (CTX). 2. The MIC-range, MIC50 and MIC90 of these 3 drugs of carbapenems (MEPM, IPM and PAPM) were different against Escherichia coli and Haemophilus influenzae which are Gram-negative strains. The MIC90 of MEPM was < or = 0.025 microgram/ml and those of IPM and PAPM were 0.2 microgram/ml against E. coli. The MIC90 of MEPM was 0.1 microgram/ml, that of IPM was 25 micrograms/ml and that of PAPM was 6.25 micrograms/ml against H. influenzae. Thus, the antimicrobial activity of MEPM was stronger than those of IPM and PAPM. The MIC90's of IPM and PAPM against H. influenzae were high with the MIC of IPM at 12.5 approximately 25 micrograms/ml and the MIC of PAPM at 3.13 approximately 12.5 micrograms/ml against 3 IPM-resistant strains among 17 isolates. 3. The MIC90 of ABPC was 0.39 microgram/ml and that of CTX was 0.1 microgram/ml against 20 strains of S. pneumoniae including 6 strains of PCG-insensitive or resistant S. pneumoniae. The MIC90 of ABPC and CTX were higher than those of 3 carbapenem drugs. There were E. coli of 8 strains with ABPC-high resistance (the MIC of ABPC was > 100 micrograms/ml) and 2 strains for which MIC of CTX were 0.39 microgram/ml and 3.13 micrograms/ml. It was found that 29.4% of H. influenzae were beta-lactamase producing strains. 4. It appeared that antimicrobial activities of carbapenems, particularly MEPM were strong against clinical isolates from blood and cerebrospinal fluid. MEPM will be first choice drug by empiric therapy in infections including sepsis and purulent meningitis.

Topics: Ampicillin; Blood; Cefotaxime; Cephalosporins; Cerebrospinal Fluid; Escherichia coli; Humans; Imipenem; Listeria monocytogenes; Meningitis, Bacterial; Meropenem; Penicillins; Sepsis; Streptococcus agalactiae; Streptococcus pneumoniae; Thienamycins

Topics: Abdomen; Bacterial Infections; Drug Approval; Humans; Meningitis, Bacterial; Meropenem; Thienamycins; United States; United States Food and Drug Administration

This paper on bacterial meningitis looks at aspects inherent in the aetiology and mechanisms underlying neurological damage and pharmacological treatment. Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis are the pathogens most commonly responsible and are able to colonise the host's respiratory mucosae, invade the vascular space, cross the haematoliquoral barrier and survive in the cerebrospinal fluid. The presence of germs in the subarachnoid spaces leads to the onset of inflammation and neurological damage. The most often used pharmacological treatments include, apart from antibiotics, anti-inflammatory drugs (although we have clinical data for corticosteroids only), pentoxyphillin and monoclonal antibodies. Initially empiric, antibiotic therapy is based on the use of drugs that act against the probable pathogenic agents, are capable of surmounting the haematoliquoral barrier and are well tolerated. Prior to the Eighties, the antibiotic of choice was ampicillin associated or otherwise with aminoglycosides. Subsequently, the availability of new drugs (cefotaxime and ceftriaxone) and the appearance of resistance led to changes in therapeutic protocols. Of the carbapenemics, wide spectrum antibiotics with high resistance to beta lactamase, imipenem /cilastatin proved effective although there was a high risk of inducing convulsions in patients with previous neurological damage or kidney failure. Meropenem was able to surmount the haematoliquoral barrier in sufficient concentrations and was well tolerated in patients with prior neurological changes. It has proved effective in clinical studies carried out up to the present.

Topics: Aminoglycosides; Ampicillin; Anti-Bacterial Agents; Ceftriaxone; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Escherichia coli; Haemophilus influenzae; Humans; Imipenem; Meningitis, Bacterial; Meropenem; Neisseria meningitidis; Streptococcus pneumoniae; Thienamycins

Topics: Campylobacter fetus; Campylobacter Infections; Drug Resistance, Microbial; Humans; Infant, Newborn; Meningitis, Bacterial; Meropenem; Thienamycins

Meropenem and comparator antibiotics, including ceftriaxone, ceftazidime, benzyl penicillin and a combination of ampicillin plus gentamicin, were evaluated in a model of bacterial meningitis in the guinea-pig. The model is an acute infection in which challenge with each organism, if untreated, causes an increase in numbers of white blood cells, elevation of protein concentrations and 6-8 log10 cfu/mL of bacteria in the CSF. Infections caused by Haemophilus influenzae, Neisseria meningitidis, three strains of Streptococcus pneumoniae (two penicillin-resistant), Escherichia coli, Pseudomonas aeruginosa and Listeria monocytogenes all responded to meropenem, which was as active as the comparator agents in all studies, and was more active in most. Of particular note were the results seen against S. pneumoniae (penicillin-resistant) infections, in which meropenem was significantly more effective than ceftriaxone. Also notable were results from the P. aeruginosa infection where meropenem, at low doses, was more effective than ceftazidime. Activity against L. monocytogenes was equivalent to that produced by treatment with the combination of ampicillin plus gentamicin, even when treatment was delayed. These results show that, in an animal model, meropenem penetrates into CSF in concentrations sufficient to produce significant reductions in the numbers of common and less common pathogens.

Topics: Ampicillin; Animals; Carbapenems; Ceftazidime; Ceftriaxone; Cephalosporins; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Drug Evaluation; Drug Resistance, Microbial; Escherichia coli Infections; Gentamicins; Guinea Pigs; Haemophilus Infections; Haemophilus influenzae; Listeriosis; Meningitis, Bacterial; Meropenem; Neisseria meningitidis; Penicillin G; Pneumococcal Infections; Thienamycins

Topics: Accidental Falls; Adult; Brain Injuries; Cross Infection; Humans; Male; Meningitis, Bacterial; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins

In a rabbit Escherichia coli meningitis model, endotoxin liberation and concentrations of leukocytes, tumor necrosis factor (TNF), and lactate were compared after a single intravenous dose of cefotaxime, cefpirome, meropenem, chloramphenicol, or gentamicin. These antibiotics caused a 2- to 10-fold increase in cerebrospinal fluid concentrations of free (filterable) endotoxin within 2 h of starting treatment. By contrast, free endotoxin concentrations increased almost 100-fold in untreated animals 4 h later as bacteria continued to multiply. An initial enhancement of inflammation in the central nervous system occurred in all treatment groups compared with untreated controls. No significant differences were observed between treatment groups except for lower TNF concentrations in chloramphenicol-treated animals. Antibiotic therapy in E. coli meningitis, irrespective of the agent used, may result in an increase in free endotoxin and enhancement of inflammation, but the amount of endotoxin liberated is considerably smaller than that shed by untreated bacteria.

Topics: Animals; Anti-Bacterial Agents; Cefotaxime; Cefpirome; Cephalosporins; Chloramphenicol; Endotoxins; Escherichia coli Infections; Gentamicins; Inflammation; Male; Meningitis, Bacterial; Meropenem; Rabbits; Thienamycins

Topics: Adult; Humans; Male; Meningitis, Bacterial; Meropenem; Pseudomonas Infections; Thienamycins

Pharmacokinetic and clinical studies on meropenem (MEPM, SM-7338), a new developed carbapenem, were performed and the following results were obtained. 1. Absorption/excretion: Pharmacokinetics of MEPM was studied in 9 children using doses of 10 mg/kg and 20 mg/kg by a 30 minute-drip infusion. Peak plasma levels and plasma half-lives of the 2 doses were 28.4 and 43.0 micrograms/ml, and 0.70 and 0.80 hours, respectively. Their urinary recovery rates were 42.5 to 67.6% and 29.9 to 62.6%, respectively. Cerebrospinal fluid levels and penetration rates of MEPM in a patient with purulent meningitis were 0.66 to 4.01 micrograms/ml and 1.6 to 12.2%, respectively. 2. Clinical study: Forty-nine patients were treated with MEPM at doses exceeding 100 mg/kg/day with purulent meningitis and 30 to 60 mg/kg/day with other infections. MEPM gave "excellent" or "good" responses in 48 cases, an efficacy rate of 98.0%. Only one patient with subdural abscess showed fair response. Diarrhea and rash were observed in 1 case each. Abnormal laboratory test results were noted in 5 patients including elevation of GOT, GPT and eosinophils. In no cases the treatment had to be discontinued.

Topics: Absorption; Adolescent; Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Female; Half-Life; Humans; Infant; Liver; Male; Meningitis, Bacterial; Meropenem; Thienamycins

A new carbapenem antibiotic, meropenem (MEPM), was evaluated for its safety and efficacy in 33 infants and children. MEPM was effective in all the 32 evaluable cases including 4 cases of bacterial meningitis and 5 cases of Pseudomonas aeruginosa infections. The mean half life of plasma concentrations of MEPM was 0.84 +/- 0.09 hours after 30 minutes intravenous drip infusion. Mild diarrhea (2 cases), transient elevation of transaminases (8 cases), and transient eosinophilia (2 cases) were associated with the MEPM therapy, but none of them was problematic. These data suggest that MEPM is safe in infants and children and could be one of the therapeutic agents for severe infections or infections in compromised hosts.

Topics: Adolescent; Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Female; Half-Life; Humans; Infant; Male; Meningitis, Bacterial; Meropenem; Pseudomonas Infections; Thienamycins