meropenem and Staphylococcal-Infections

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

Pharmacokinetic and clinical evaluations in pediatrics were made on meropenem (SM-7338, MEPM), a new parenteral dehydropeptidase-1 stable carbapenem used without any inhibitors, at 33 medical institutions. The results are summarized as follows. 1. Pharmacokinetic studies. MEPM at a dose of 10, 20, or 40 mg/kg was administered to 53 children by 30-minute drip infusion. Peak plasma concentrations (Cmax's) and plasma half-lives (T1/2's) of these doses were 28.5, 47.2 and 130.0 micrograms/ml, and 0.80, 0.93 and 0.94 hours, respectively. A clear dose response was observed in Cmax's and T1/2 values were quite similar to those observed in adults. In the first 6 hours after administration, 54.4 to 68.1% of the administered drug was recovered in urine. The cerebrospinal fluid (CSF) levels of MEPM in patients with purulent meningitis were 0.13 microgram/ml at a dose of 6 mg/kg, and 0.64 to 4.22 micrograms/ml at a dose of 29 to 44 mg/kg within day 4 of onset. The penetration rate of MEPM showed an intermediate value among those for other cephalosporin antibiotics. 2. Clinical study. Clinical efficacies of MEPM were evaluated in 389 cases. The most common doses used were 10 to 20 mg/kg/once, 2 to 3 times a day. The maximum dose was 173 mg/kg/day q.i.d. MEPM gave "excellent" or "good" responses in 242 (97.6%) out of 248 cases in which causative organisms were documented and in 134 (95.0%) out of 141 cases in which causative organisms were not identified. Clinical efficacy rates were 100% in 11 patients with purulent meningitis, 85.7% in 7 with septicemia, 98.8% in 173 with pneumonia, and 100% in 65 with UTI. Bacteriologically, 260 strains (96.7%) out of 269 strains were eradicated by MEPM treatment. Eradication rates were 89.2% for Staphylococcus aureus (37 strains) and 100% for Streptococcus pneumoniae (35 strains). The overall eradication rate for Gram-positive bacteria was 94.6%. Among Gram-negative bacteria, 98.3% out of 172 strains were eradicated. The eradication rate of Haemophilus influenzae (73 strains) was 98.6% and Pseudomonas aeruginosa (11 strains) was 90.9%, and all of Branhamella catarrhalis (15 strains), Escherichia coli (42 strains), and Klebsiella pneumoniae (6 strains) were eradicated. Out of 84 cases for which previous antibiotic therapies of 3 days or longer were not successful, MEPM gave "excellent" or "good" responses in 77 cases (91.7%) and excellent bacteriological responses (95.7%).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Bacterial Infections; Child; Child, Preschool; Escherichia coli Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Moraxella catarrhalis; Neisseriaceae Infections; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections; Thienamycins

The authors report three trials of B-lactams and carbapenems for soft tissue infections treated on a surgical service: 1) cefmetazole versus cefoperazone, n = 44; 2) cefotetan versus cefoxitin, n = 24; and 3) meropenem versus imipenem, n = 44. A total of 138 hospitalized patients were enrolled with 112 meeting evaluability criteria. Four hundred twenty-three isolates were cultured (mean, three/patient) of which 67 per cent were aerobes and 33 per cent anaerobes. Cure rates for each trial were: 1) 93 per cent; 2) 92 per cent; 3) 100 per cent. Failures were caused by resistant organisms (Streptococcus group D, Bacteroides fragilis and Pseudomonas) appearing in incompletely drained infection sites. Three patients receiving meropenem had adverse effects (headache, nausea) and one receiving cefoxitin (truncal rash). Operative drainage and debridement remain the critical elements in therapy. Agents with longer half lives allowing twice daily dosing (cefmetazole and cefotetan) were as effective and less expensive than multiple doses of short-acting agents. The extended spectrum carbapenems are most useful for severe infections or resistant organisms.

Topics: Adult; Aged; Bacterial Infections; Carbapenems; Cefmetazole; Cefoperazone; Cefotetan; Cefoxitin; Cephalosporins; Drug Combinations; Drug Resistance, Microbial; Escherichia coli Infections; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Prospective Studies; Remission Induction; Skin Diseases, Infectious; Staphylococcal Infections; Streptococcal Infections; Thienamycins

Respiratory infections are the most frequent cause of hospitalization in tracheostomized children. However, there is a lack of publications to guide their management. The primary objective was to describe the microbiological isolates and their antibiotic susceptibilities of bacterial respiratory infections in a population of tracheostomized children.. The study analyzed 328 respiratory infection episodes: 164 tracheobronchitis (50%), 112 nonspecific respiratory episodes (34.1%), and 52 pneumonias (15.9%). The most commonly isolated microorganisms were Pseudomonas aeruginosa, Serratia marcescens, and Staphylococcus aureus. The antibiotics that exhibited the highest effectiveness were meropenem (92%), imipenem (87%), and levofloxacin (86%). When hospitalization exceeded 7 days, there was a higher chance of isolating Escherichia coli and Klebsiella pneumoniae (p < 0.001 and p = 0.001, respectively), as well as an increased rate of multidrug resistance (27% vs. 7%, p = 0.035). In 75.3% of cases, the microorganism had been previously isolated in a sample taken 7-30 days before the current one, with a higher frequency observed in the case of P. aeruginosa (95.2%) compared to other microorganisms (65.3%, p < 0.001).. Meropenem, imipenem, and levofloxacin provided the most effective coverage for these infections. The risk of multidrug resistance increased with longer hospital stays, especially for E. coli and K. pneumoniae. Recent isolation of P. aeruginosa may justify empirical coverage.

Topics: Adolescent; Anti-Bacterial Agents; Child; Drug Resistance, Bacterial; Escherichia coli; Follow-Up Studies; Humans; Imipenem; Klebsiella pneumoniae; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Respiratory Tract Infections; Retrospective Studies; Staphylococcal Infections; Uncertainty

The genus

Topics: Animals; Anti-Bacterial Agents; Artocarpus; Biofilms; Flavonoids; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus

Antimicrobial resistance is associated with increased morbidity in secondary infections and is a global threat owning to the ubiquitous nature of resistance genes in the environment. Recent estimate put the deaths associated with bacterial antimicrobial resistance in 2019 at 4.95 million worldwide. Lymphatic filariasis (LF), a Neglected Tropical Disease (NTD), is associated with the poor living in the tropical regions of the world. LF patients are prone to developing acute dermatolymphangioadenitis (ADLA), a condition that puts them at risk of developing secondary bacterial infections due to skin peeling. ADLA particularly worsens the prognosis of patients leading to usage of antibiotics as a therapeutic intervention. This may result in inappropriate usage of antibiotics due to self-medication and non-compliance; exacerbating antimicrobial resistance in LF patients. In this perspective, we assessed the possibilities of antimicrobial resistance in LF patients. We focused on antibiotic usage, antibiotic resistance in Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa isolates and looked at genes (mecA and Extended-spectrum beta-lactamase [blaCTX-M, blaSHV and blaTEM]) coding for resistance in multi-drug resistant (MDR) bacterial isolates.. Of the sixty (60) participants, fifty-four (n = 54, 90%) were within 31-60 years of age, twenty (n = 20, 33.33%) were unemployed and thirty-eight (n = 38, 50.67%) had wounds aged (in months) seven (7) months and above. Amoxicillin (54%) and chloramphenicol (22%) were the most frequently used antibiotics for self-medication. Staphylococcus aureus isolates (n = 26) were mostly resistant to penicillin (n = 23, 88.46%) and least resistant to erythromycin (n = 2, 7.69%). Escherichia coli isolates (n = 5) were resistant to tetracycline (n = 5, 100%) and ampicillin (n = 5, 100%) but were sensitive to meropenem (n = 5, 100%). Pseudomonas aeruginosa isolates (n = 8) were most resistant to meropenem (n = 3, 37.50%) and to a lesser ciprofloxacin (n = 2, 25%), gentamicin (n = 2, 25%) and ceftazidime (n = 2, 25%). Multi-drug resistant methicillin resistant Staphylococcus aureus (MRSA), cephalosporin resistant Escherichia coli. and carbapenem resistant Pseudomonas aeruginosa were four (n = 4, 15.38%), two (n = 2, 40%) and two (n = 2, 25%) respectively. ESBL (blaCTX-M) and mecA genes were implicated in the resistance mechanism of Escherichia coli and MRSA, respectively.. The findings show presence of MDR isolates from LF patients presenting with chronic wounds; thus, the need to prioritize resistance of MDR bacteria into treatment strategies optimizing morbidity management protocols. This could guide antibiotic selection for treating LF patients presenting with ADLA.

Topics: Amoxicillin; Ampicillin; Anti-Bacterial Agents; Bacteria; beta-Lactamases; Ceftazidime; Chloramphenicol; Ciprofloxacin; Elephantiasis, Filarial; Erythromycin; Escherichia coli; Escherichia coli Infections; Gentamicins; Ghana; Humans; Infant; Meropenem; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Penicillins; Pseudomonas aeruginosa; Staphylococcal Infections; Staphylococcus aureus; Tetracyclines

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Antifungal Agents; Antimicrobial Stewardship; Aspergillosis; Azithromycin; Bacterial Infections; Cohort Studies; Coinfection; COVID-19; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Germany; Humans; Klebsiella Infections; Linezolid; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Practice Patterns, Physicians'; Retrospective Studies; SARS-CoV-2; Staphylococcal Infections; Streptococcal Infections; Sulbactam; Vancomycin; Young Adult

A major determinant of β-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA) is the drug insensitive transpeptidase, PBP2a, encoded by mecA. Full expression of the resistance phenotype requires auxiliary factors. Two such factors, auxiliary factor A (auxA, SAUSA300_0980) and B (auxB, SAUSA300_1003), were identified in a screen against mutants with increased susceptibility to β-lactams in the MRSA strain, JE2. auxA and auxB encode transmembrane proteins, with AuxA predicted to be a transporter. Inactivation of auxA or auxB enhanced β-lactam susceptibility in community-, hospital- and livestock-associated MRSA strains without affecting PBP2a expression, peptidoglycan cross-linking or wall teichoic acid synthesis. Both mutants displayed increased susceptibility to inhibitors of lipoteichoic acid (LTA) synthesis and alanylation pathways and released LTA even in the absence of β-lactams. The β-lactam susceptibility of the aux mutants was suppressed by mutations inactivating gdpP, which was previously found to allow growth of mutants lacking the lipoteichoic synthase enzyme, LtaS. Using the Galleria mellonella infection model, enhanced survival of larvae inoculated with either auxA or auxB mutants was observed compared with the wild-type strain following treatment with amoxicillin. These results indicate that AuxA and AuxB are central for LTA stability and potential inhibitors can be tools to re-sensitize MRSA strains to β-lactams and combat MRSA infections.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactams; Cefoxitin; Cell Wall; DNA, Bacterial; Drug Resistance, Bacterial; Humans; Larva; Lipopolysaccharides; Membrane Proteins; Meropenem; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Models, Animal; Moths; Mutation; Octoxynol; Oxacillin; Penicillin-Binding Proteins; Peptidoglycan; Phenotype; Staphylococcal Infections; Teichoic Acids; Virulence

We investigated the synergistic effect between vancomycin and β-lactams against vancomycin-susceptible (VSSA) and nonsusceptible MRSA isolates [heterogeneous vancomycin-intermediate S. aureus (hVISA) and VISA].. A total of 29 MRSA, including 6 VISA, 14 hVISA, and 9 VSSA isolates, were subjected to a microbroth dilu- tion-minimum inhibitory concentration (MIC) checkerboard using vancomycin combined with cefotaxime, imipenem, or meropenem. To confirm synergistic activity, the representative strains of VISA, hVISA, and VSSA were then selected for the time-kill curve method.. The combination of vancomycin with imipenem, meropenem, or cefotaxime exhibited synergistic effects against 17 (2 VISA, 9 hVISA, and 6 VSSA), 14 (3 VISA, 9 hVISA and 2 VSSA), and 5 (3 VISA and 2 hVISA) isolates, respectively. Additive and indifferent effects were found in the remaining isolates, but no antagonistic effect was observed. Using time-kill assay, the vancomycin combined with either imipenem or cefotaxime demonstrated synergism against both VISA and hVISA isolates, while the synergistic effect with meropenem was obtained only in the VISA isolates.. This study demonstrated in vitro enhanced antibacterial activity of vancomycin plus β-lactams against clinical hVISA or VISA isolates. These combinations may be an alternative treatment for MRSA infections in clinical practice.

Topics: Anti-Bacterial Agents; beta-Lactams; Cefotaxime; Drug Synergism; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus; Vancomycin; Vancomycin Resistance

To evaluate the activity of the reported synergistic and collaterally sensitive antibiotic combination, meropenem/piperacillin/tazobactam (ME/PI/TZ), against a panel of methicillin-resistant Staphylococcus aureus (MRSA) and other methicillin-resistant Staphylococcus species; and to investigate the relationship between ME/PI/TZ susceptibility and the genomic background of clinical isolates of MRSA.. ME/PI/TZ combination and single drug minimum inhibitory concentrations (MICs) were determined for 207 strains (including 121 MRSA, 4 methicillin-sensitive S. aureus [MSSA], 37 vancomycin-intermediate S. aureus [VISA], 6 ceftaroline non-susceptible MRSA, 29 coagulase-negative staphylococci [CoNS], 5 S. pseudointermedius and 5 vancomycin-resistant Enterococci [VRE]) by broth microdilution. Whole genomes of 168 S. aureus strains were sequenced, assembled, and comparatively analysed.. USA300-SCCmec type IV isolates, clonal complex 8 (CC8)-MRSA isolates, including some VISA and ceftaroline (CPT)-intermediate strains, and all tested methicillin-resistant S. epidermidis isolates were highly susceptible to ME/PI/TZ. Isolates with elevated MICs (MICs of >16/16/16 mg/L) clustered with the USA100-SCCmec type II strain. Susceptibility of MRSA to ME/PI/TZ was correlated with susceptibility to ME. No obvious cross-resistance to CPT was observed among high-ME/PI/TZ MIC isolates.. The ME/PI/TZ combination is effective against a variety of clinical MRSA isolates, particularly of the USA300 lineage, which is expanding worldwide. ME/PI/TZ is also effective against drug-resistant CoNS and S. pseudintermedius clinical isolates.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Genome, Bacterial; Genomics; Humans; Meropenem; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Piperacillin; Staphylococcal Infections; Staphylococcus; Staphylococcus epidermidis; Tazobactam; Vancomycin-Resistant Enterococci; Whole Genome Sequencing

Topics: Abdomen; Adult; Anti-Bacterial Agents; Clindamycin; Coinfection; Debridement; Diabetes Mellitus, Type 2; Fasciitis, Necrotizing; Female; Fluid Therapy; Humans; Meropenem; Methicillin-Resistant Staphylococcus aureus; Obesity; Renal Insufficiency, Chronic; Resuscitation; Staphylococcal Infections; Streptococcal Infections; Streptococcus pyogenes; Vancomycin

The rapid emergence of methicillin-resistant Staphylococcus aureus (MRSA) strains has undermined the therapeutic efficacy of existing β-lactam antibiotics (BLAs), prompting an urgent need to discover novel BLAs adjuvants that can potentiate their anti-MRSA activities. In this study, cytotoxicity and antibacterial screening of a focused compound library enabled us to identify a compound, namely 28, which exhibited low cytotoxicity against normal cells and robust in vitro bactericidal synergy with different classes of BLAs against a panel of multidrug-resistant clinical MRSA isolates. A series of biochemical assays and microscopic studies have revealed that compound 28 is likely to interact with the S. aureus FtsZ protein at the T7-loop binding pocket and inhibit polymerization of FtsZ protein without interfering with its GTPase activity, resulting in extensive delocalization of Z-ring and morphological changes characterized by significant enlargement of the bacterial cell. Animal studies demonstrated that compound 28 had a favorable pharmacokinetic profile and exhibited potent synergistic efficacy with cefuroxime antibiotic in a murine systemic infection model of MRSA. Overall, compound 28 represents a promising lead of FtsZ inhibitor for further development of efficacious BLAs adjuvants to treat the staphylococcal infection.

Topics: Animals; Bacterial Proteins; beta-Lactams; Binding Sites; Cefuroxime; Cytoskeletal Proteins; Drug Synergism; Methicillin-Resistant Staphylococcus aureus; Mice; Small Molecule Libraries; Staphylococcal Infections; Staphylococcus aureus

A 17-year-old woman was admitted to our hospital because of a high fever, consciousness disturbance, and delirious behavior. Methicillin susceptible Staphylococcus aureus (MSSA) infection was confirmed by blood culture. Transthoracic echocardiogram showed no abnormality at first. Diffusion-weighted brain MRI showed a high intensity lesion in the middle portion of the splenium, which was shown as low intensity on apparent diffusion coefficient map. Then, antibiotics therapy was started against suspected bacterial meningitis, while the lumbar puncture was not performed because of the decreased number of platelets. Since the systolic murmur appeared at the apex on day 12, the diagnosis with infectious endocarditis was made by transthoracic echocardiogram. The MRI abnormalities disappeared on day 16 and we diagnosed her with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) associated with infectious endocarditis. This case suggests that MERS can occur associated with infectious endocarditis caused by Staphylococcus aureus.

Topics: Adolescent; Anti-Bacterial Agents; Corpus Callosum; Diffusion Magnetic Resonance Imaging; Drug Therapy, Combination; Echocardiography; Endocarditis, Bacterial; Female; Humans; Infectious Encephalitis; Meropenem; Mitral Valve Annuloplasty; Severity of Illness Index; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

OBJECTIVE To evaluate the effects of vaporized hydrogen peroxide (VHP) sterilization on the in vitro antimicrobial efficacy of meropenem-impregnated polymethyl methacrylate (M-PMMA) beads. SAMPLE 6-mm-diameter polymethyl methacrylate beads that were or were not impregnated with meropenem. PROCEDURES Meropenem-free polymethyl methacrylate and M-PMMA beads were sterilized by use of an autoclave or VHP or remained unsterilized. To determine the antimicrobial efficacy of each bead-sterilization combination (treatment), Mueller-Hinton agar plates were inoculated with 1 of 6 common equine pathogens, and 1 bead from each treatment was applied to a sixth of each plate. The zone of bacterial inhibition for each treatment was measured after 24 hours. To estimate the duration of antimicrobial elution into a solid or liquid medium, 1 bead from each treatment was transferred every 24 hours to a new Staphylococcus aureus-inoculated agar plate or a tube with PBS solution, and an aliquot of the eluent from each tube was then applied to a paper disc on an S aureus-inoculated agar plate. All agar plates were incubated for 24 hours, and the zone of bacterial inhibition was measured for each treatment. RESULTS In vitro antimicrobial efficacy of M-PMMA beads was retained following VHP sterilization. The duration of antimicrobial elution in solid and liquid media did not differ significantly between unsterilized and VHP-sterilized M-PMMA beads. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that M-PMMA beads retained in vitro antimicrobial activity and eluted the drug for up to 2 weeks after VHP sterilization.

Topics: Animals; Anti-Bacterial Agents; Horse Diseases; Horses; Hydrogen Peroxide; In Vitro Techniques; Meropenem; Microspheres; Osteomyelitis; Polymethyl Methacrylate; Staphylococcal Infections; Staphylococcus aureus; Sterilization

Topics: Aged; Anti-Bacterial Agents; Craniotomy; Drug Resistance, Multiple, Bacterial; Empyema; Enterobacteriaceae Infections; Humans; Male; Meningeal Neoplasms; Meropenem; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Seizures; Spinal Puncture; Staphylococcal Infections; Surgical Wound Infection; Treatment Outcome; Vancomycin

Methicillin and vancomycin resistant Staphylococcus aureus infections are an emerging global health concern leading to increasing morbidity and mortality. Continuous increase in drug resistance has underlined the need for discovery and development of new antibacterial agents acting via novel mechanisms to overcome this pressing issue. In this context, a number of 1,2,3-triazole linked 4(3H)-quinazolinone derivatives were designed and synthesized as potent antibacterial agents. When evaluated against ESKAP pathogen panel, compounds 7a, 7b, 7c, 7e, 7f, 7g, 7h, 7i, 9a, 9c, 9d and 9e exhibited significantly selective inhibitory activities towards Staphylococcus aureus (MIC = 0.5-4 μg/mL). To understand and confirm the specificity of these compounds, the compounds 7a and 9a were tested against E. coli and A. baumannii in combination with sub-lethal concentrations of Polymyxin B nonapeptide (PMBN) and were found to be inactive. This clearly indicated that these compounds possess specific and potent activity towards S. aureus and are inactive against gram-negative pathogens. Encouragingly, the compounds were also found to be non toxic to Vero cells and displayed favourable selectivity index (SI = 40 to 80). Furthermore, 7a and 9a were found to possess potent inhibitory activity when tested against multidrug resistant S. aureus including strains resistant to vancomycin (MIC values 0.5-32 μg/mL), indicating that the compounds are able to escape current drug-resistance mechanisms. With the potent anti-bacterial activity exhibited the new series of 1,2,3-triazole linked 4(3H)-quinazolinones have emerged as promising candidates for treating multidrug resistant Staphylococcus aureus infections.

Topics: Anti-Bacterial Agents; Dose-Response Relationship, Drug; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Structure; Quinazolinones; Staphylococcal Infections; Structure-Activity Relationship; Triazoles

Raoultella Ornithinolytica (RO) is an encapsulated, Gram- negative, nonmotile aerobic rob which was reclassified from Klepsiella genus belonging in the family of Enterobacteriaceae. It is a rare human infection and few cases have been reported in post thoracotomy patients. Here we present a case of a left lower lobectomy patient that was complicated by pleural effusion and high fever with positive sputum cultures of Raoultella Ornithinolytica and positive pleural fluid cultures of Staphylococcus hominis. It is related with aquatic life poisoning. There are few cases reported and even fewer postoperatively. The infection is rare in human therefore the bacteria is still underreported.

Topics: Aged; Anti-Bacterial Agents; Carcinoma, Non-Small-Cell Lung; Ciprofloxacin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Male; Meropenem; Pleural Effusion; Postoperative Complications; Sputum; Staphylococcal Infections; Staphylococcus hominis; Treatment Outcome

The combination of piperacillin/tazobactam (TZP) and vancomycin (VAN) provides a wide spectrum of activity against many pathogens acquired in healthcare settings. However, there have been reports of increased potential for nephrotoxicity with this combination. The aim of this study was to evaluate the nephrotoxic effect of TZP+VAN and to compare it with that of TZP and VAN monotherapies as well as VAN + meropenem (MEM), another broad-spectrum combination. A total of 402 patients receiving any of the antimicrobial regimens for >48 h were evaluated retrospectively over a 2-year period (2012-2013). Patients admitted to the intensive care unit, those with a baseline serum creatinine >2.0 mg/dL, patients on haemodialysis or peritoneal dialysis, pregnant women and those in septic shock were excluded. The presence and severity of acute kidney injury (AKI) was assessed according to the AKIN criteria. The incidence of AKI was significantly higher in the TZP+VAN group (41.3%) compared with the TZP (16.0%), VAN (15.7%) and VAN+MEM (10.1%) groups (P < 0.001). In the multivariate analysis, the risk of AKI increased 3.5-fold in patients treated with TZP+VAN and 1.7-fold in those who were receiving a potentially nephrotoxic drug when the antibiotic regimen was started compared with patients treated with VAN alone. Combined use of TZP+VAN carries a much higher risk of AKI than either antibiotic monotherapy regimen. Therefore, this broad-spectrum combination should be used cautiously in patients with a high likelihood of developing kidney injury.

Topics: Acute Kidney Injury; Adult; Aged; Creatinine; Drug Therapy, Combination; Female; Humans; Kidney; Logistic Models; Male; Meropenem; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Staphylococcal Infections; Thienamycins; Vancomycin

An 87-year-old woman presented to the emergency department with a 2-week history of progressively worsening shortness of breath, fever and generalised myalgia. She underwent a transcatheter Portico aortic valve implantation for severe symptomatic aortic stenosis 3 months prior to this presentation. Examination revealed a temperature of 40°C and a systolic murmur in the aortic area. Inflammatory markers were elevated, and blood cultures were positive for methicillin-sensitive

Topics: Aged, 80 and over; Anti-Bacterial Agents; Aortic Valve; Daptomycin; Echocardiography, Transesophageal; Endocarditis, Bacterial; Female; Heart Valve Prosthesis; Humans; Meropenem; Prosthesis-Related Infections; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Transcatheter Aortic Valve Replacement

Topics: Anti-Bacterial Agents; Child; Craniotomy; Drainage; Endoscopy; Epidural Abscess; Female; Fusobacterium Infections; Humans; Magnetic Resonance Imaging; Meropenem; Paranasal Sinuses; Pott Puffy Tumor; Staphylococcal Infections; Thienamycins; Tomography, X-Ray Computed; Vancomycin

To find the most prevalent organism in diabetic foot ulcers and its drug sensitivity and resistance to different standard antibiotics.. Adescriptive and cross-sectional study.. Ward 7, Jinnah Postgraduate Medical Center, Karachi, from December 2010 to December 2012.. Ninety-five diabetic patients with infected foot wounds of Wegener grade 2 - 5 who had not received any previous antibiotics were included in the study by consecutive sampling. Pus culture specimen from wounds was taken and the organism isolated was identified. Also the most sensitive group of antibiotics and the most resistant one to that organism was noted.. Staphylococcus aureuswas the most prevalent organism constituting 23.16% (n=22) of the organisms isolated; Escherichia coli with 17.89% (n=17) and Klebsiella with 12.63% (n=12) followed. Males presented more with diabetic foot (n=52) out of 95 patients. The most common age group affected was 41 - 60 years (73 patients). The organisms were most sensitive to Meropenem, effective in 90 (95%) patients and most resistant to Cotrimoxazole (80, 84% patients). Out of the 95 patients, 39 (41%) patients were hypertensive, 30 (31.5%) were obese and 14 (15%) were smokers. Staphylococcus aureus was the most prevalent organism overall irrespective to gender, age groups and co-morbidity of the patients.. Staphylococcus aureuswas the most frequent organism in diabetic foot ulcers; the most effective antibiotic is Meropenem and least effective is Cotrimoxazole.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Cross-Sectional Studies; Diabetic Foot; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella; Klebsiella Infections; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pakistan; Prevalence; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Wound Infection

Infection is a major determinant of clinical outcome among patients in the intensive care unit. However, these data are lacking in most developing countries; hence, we set out to describe the profile of nosocomial infection in one of the major tertiary hospitals in northern Nigeria.. Case records of patients who were admitted into the intensive care unit over a 4-year period were retrospectively reviewed. A preformed questionnaire was administered, and data on clinical and microbiological profile of patients with documented infection were obtained.. Eighty-our episodes of nosocomial infections were identified in 76 patients. Road traffic accident (29/76, 38.2%) was the leading cause of admission. The most common infections were skin and soft tissue infections (30/84, 35.7%) followed by urinary tract infection (23/84, 27.4%). The most frequent isolates were Staphylococcus aureus (35/84, 41.7%), Klebsiella pneumoniae (18/84, 21.4%), and Escherichia coli (13/84, 15.5%). High rate of resistance to cloxacillin (19/35, 54.3%) and cotrimoxazole (17/26, 65.4%) was noted among the S aureus isolates. All the Enterobacteriaceae isolates were susceptible to meropenem, whereas resistance rate to ceftriaxone was high (E coli, 55.6%; K pneumoniae, 71.4%; Proteus spp, 50%).. Infection control practice and measures to curtail the emergence of antimicrobial resistance need to be improved.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Catheter-Related Infections; Ceftriaxone; Cloxacillin; Cross Infection; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Nigeria; Pneumonia, Bacterial; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection; Tertiary Care Centers; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Young Adult

Drug resistant infections are becoming common worldwide and new strategies for drug development are necessary. Here, we report the synthesis and evaluation of 2,4-dinitrophenylsulfonamides, which are donors of sulfur dioxide (SO2), a reactive sulfur species, as methicillin-resistant Staphylococcus aureus (MRSA) inhibitors. N-(3-Methoxyphenyl)-2,4-dinitro-N-(prop-2-yn-1-yl)benzenesulfonamide (5e) was found to have excellent in vitro MRSA inhibitory potency. This compound is cell permeable and treatment of MRSA cells with 5e depleted intracellular thiols and enhanced oxidative species both results consistent with a mechanism involving thiol activation to produce SO2.

Topics: Anti-Bacterial Agents; Drug Design; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Prodrugs; Staphylococcal Infections; Structure-Activity Relationship; Sulfhydryl Compounds; Sulfur Dioxide

Topics: Abdominal Abscess; Anti-Bacterial Agents; Cellulitis; Clindamycin; Combined Modality Therapy; Common Variable Immunodeficiency; Debridement; Drug Substitution; Female; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Infusions, Subcutaneous; Meropenem; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Necrosis; Pyoderma Gangrenosum; Reoperation; Staphylococcal Infections; Thienamycins; Vancomycin; Wound Infection

Invasive infections due to carbapenem-resistant Enterobacteriaceae (CRE) are becoming increasingly more prevalent and provide significant morbidity and mortality. Providing curative therapy and overcoming bacterial resistance are difficult tasks with limited antibiotic options. Alternative antibiotics and approaches to therapy are required, with often a compromise in patient outcome.. To demonstrate the effective use of therapeutic drug monitoring (TDM) in difficult-to-treat infections due to multiresistant gram-negative bacteria.. A case of an elderly woman with an invasive cervical spine infection due to CRE is presented. Her protracted therapeutic course was complicated by multiple treatment failures and severe cervical spine instability. Therapeutic success, as determined by wound healing, cervical spine stability, and continued suppression of inflammatory markers, was obtained by continuous daily ertapenem infusions with TDM guiding the optimal drug dosing.. In this unusual setting, TDM was utilized successfully to achieve favorable serum antibiotic concentrations and lead to control of the infection. TDM may be a useful tool in difficult-to-treat infections caused by multiresistant bacteria.

Topics: Amikacin; Anti-Bacterial Agents; beta-Lactams; C-Reactive Protein; Drug Monitoring; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Ertapenem; Female; Fosfomycin; Humans; Meropenem; Middle Aged; Osteomyelitis; Staphylococcal Infections; Staphylococcus epidermidis; Thienamycins

To investigate the toxicity and corneal pharmacokinetics of meropenem as a potential antimicrobial for bacterial keratitis.. Corneal epithelial cell and keratocyte toxicity was investigated using methyl thiazolyl tetrazolium (MTT) and LIVE/DEAD assays. The penetration of meropenem through the human cornea was measured using an artificial anterior chamber. In one group of corneas, the epithelial and endothelial layers were removed and in a second group these layers were left intact. We applied 50 μL (10 mg/mL) meropenem to the corneal surface and collected samples in the anterior chamber from 45 minutes up to 24 hours. Meropenem concentrations were estimated with a bioassay and HPLC.. Meropenem had significantly higher cellular metabolic activity (MTT assay) at both 5 mg/mL and 2.5 mg/mL compared with moxifloxacin (P = 0.029 and P = 0.018, respectively), with 96% cell viability (LIVE/DEAD assay). The measured values for meropenem concentrations in corneal and aqueous samples were significantly higher using a bioassay than with HPLC (P = 0.004). For both intact and denuded corneas, the concentrations in the anterior chamber increased from 0.48 μg/mL (SD 0.89) and 0.89 μg/mL (SD 0.81) to 6.35 μg/mL (SD 0.81) and 13.48 μg/mL (SD 14.82) using HPLC, and from 0.68 μg/mL (SD 1.50) and 1.31 μg/mL (SD 1.55) to 47.03 μg/mL (SD 5.51) and 43.69 μg/mL (SD 27.22) measured with a bioassay.. Meropenem has very low toxicity in vitro. It has good corneal penetration, achieving anterior chamber concentrations above MIC90 for bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, streptococci, coagulase-negative staphylococci, and the Enterobacteriaceae.

Topics: Anti-Bacterial Agents; Cells, Cultured; Epithelial Cells; Epithelium, Corneal; Eye Infections, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Keratinocytes; Keratitis; Meropenem; Microbial Sensitivity Tests; Staphylococcal Infections; Thienamycins

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

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent multidrug-resistant pathogens worldwide, exhibiting increasing resistance to the latest antibiotic therapies. Here we show that the triple β-lactam combination meropenem-piperacillin-tazobactam (ME/PI/TZ) acts synergistically and is bactericidal against MRSA subspecies N315 and 72 other clinical MRSA isolates in vitro and clears MRSA N315 infection in a mouse model. ME/PI/TZ suppresses evolution of resistance in MRSA via reciprocal collateral sensitivity of its constituents. We demonstrate that these activities also extend to other carbapenem-penicillin-β-lactamase inhibitor combinations. ME/PI/TZ circumvents the tight regulation of the mec and bla operons in MRSA, the basis for inducible resistance to β-lactam antibiotics. Furthermore, ME/PI/TZ subverts the function of penicillin-binding protein-2a (PBP2a) via allostery, which we propose as the mechanism for both synergy and collateral sensitivity. Showing in vivo activity similar to that of linezolid, ME/PI/TZ demonstrates that combinations of older β-lactam antibiotics could be effective against MRSA infections in humans.

Topics: Allosteric Regulation; Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Drug Synergism; Drug Therapy, Combination; Female; Gene Expression; Humans; Linezolid; Meropenem; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Operon; Penicillanic Acid; Penicillin-Binding Proteins; Piperacillin; Staphylococcal Infections; Tazobactam; Thienamycins

The US Food and Drug Administration reported seizures associated with the use of cefepime (primarily in patients with renal impairment who did not receive appropriate dose adjustments of cefepime).. The maximum dose of cefepime in the USA (6 g per day) is higher than that in Japan (4 g per day). We investigated the prevalence of convulsions associated with the use of cefepime by comparing it with that of meropenem.. A retrospective study was undertaken in 183 patients treated with cefepime and 745 patients treated with meropenem over 2 years at Ehime University Hospital. Cefepime or meropenem-associated convulsions were defined according to the following criteria: (1) administration or dose escalation of diazepam, phenytoin, phenobarbital and thiamylal given via the intravenous route (2) convulsions recorded in medical records during administration of cefepime or meropenem.. The prevalence of convulsions was significantly greater in the cefepime treated group than in the meropenem-treated group. Among the patients who had cefepime-associated convulsions, none had renal failure. Cefepime-associated convulsions occurred only in patients with brain disorders.. Cefepime-associated convulsions should be recognized as potential complications even in patients with normal renal function. Brain disorders may increase the risk of cefepime-associated convulsions.

Topics: Adult; Aged; Anti-Bacterial Agents; Brain Diseases; Cefepime; Cephalosporins; Female; Hospitals, University; Humans; Infusions, Intravenous; Japan; Male; Meropenem; Neurotoxicity Syndromes; Prevalence; Pseudomonas aeruginosa; Pseudomonas Infections; Renal Insufficiency; Retrospective Studies; Risk; Seizures; Staphylococcal Infections; Staphylococcus aureus; Thienamycins

To report a case of multidrug-resistant osteomyelitis successfully treated with telavancin, rifampin, and meropenem.. An 18-year-old male with spina bifida was treated primarily in the outpatient setting over the course of 133 days with multiple antimicrobials for a recurrent right calcaneal wound and osteomyelitis infection. Initial cultures were positive for methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus, which were treated with intravenous vancomycin 1 g every 12 hours, increased after 13 days to 1.5 g every 12 hours with addition of rifampin 300 mg twice daily, both of which were discontinued on day 22 due to leukopenia (white blood cell count 3.0 × 10(3)/μL) and neutropenia (absolute neutrophil count 0.2 × 10(3)/μL). Daptomycin 8 mg/kg/day was then initiated with rifampin 300 mg twice daily; treatment was discontinued after 49 days due to an elevated creatine kinase level of 1831 U/L (baseline 86). Intravenous meropenem 1 g every 8 hours was again initiated on day 83 following additional identification of quinolone-resistant Pseudomonas aeruginosa from the soft tissue of the right foot. Intravenous vancomycin 1 g every 12 hours was also restarted at this time for persistent coagulase-negative Staphylococcus and oral rifampin 300 mg twice daily was again added. Adverse events again required the discontinuation of vancomycin on day 91. The eventual drug therapy regimen consisted of telavancin 750 mg/day for 42 days, meropenem for 50 days, and oral rifampin for 50 days. At the end of treatment, the patient's right heel wound had almost completely closed. He was without recurrence or treatment-related adverse events at follow-up 1 year later.. Antimicrobial selection for osteomyelitis infections presents a challenge to the clinician due to patient intolerance, increasing antimicrobial resistance, and variable antimicrobial penetration at the site of infection. To our knowledge, this is the first case report of the successful use of a regimen including telavancin for the treatment of a recurrent, coagulase-negative Staphylococcus osteomyelitis infection.. In this complex case involving a polymicrobial infection of the right calcaneal bone and surrounding soft tissue, eventual drug therapy including telavancin, meropenem, and rifampin resulted in a successful clinical response.

Topics: Adolescent; Aminoglycosides; Anti-Bacterial Agents; Coinfection; Drug Therapy, Combination; Humans; Lipoglycopeptides; Male; Meropenem; Osteomyelitis; Rifampin; Staphylococcal Infections; Thienamycins; Treatment Outcome

The authors report a rare case of piriformis pyomyositis, in a teenage rugby player, who was initially feverish and presented to us with low back pain, sciatica and inability to mobilise due to pain. Subsequent imaging investigations (MRI scan) revealed abscess formation in the piriformis muscle with compression effect on the ipsilateral sciatic nerve. A course of intravenous antibiotic therapy followed by oral antibiotics fully resolved his symptoms and returned inflammatory markers back to normal.

Topics: Abscess; Adolescent; Anti-Bacterial Agents; Floxacillin; Football; Humans; Low Back Pain; Magnetic Resonance Imaging; Male; Meropenem; Pain; Piriformis Muscle Syndrome; Pyomyositis; Rifampin; Sciatica; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Vancomycin

Topics: Administration, Oral; Anti-Bacterial Agents; Aortic Aneurysm, Abdominal; Atherosclerosis; Blood Vessel Prosthesis Implantation; Clindamycin; Drug Therapy, Combination; Endoleak; Humans; Infusions, Intravenous; Male; Meropenem; Middle Aged; Prosthesis-Related Infections; Staphylococcal Infections; Staphylococcus epidermidis; Stents; Thienamycins; Tomography, X-Ray Computed; Vancomycin

The spectrum of disease with pandemic novel H1N1 influenza A (2009) virus ranges from non-febrile, mild upper respiratory tract infection to severe or fatal pneumonia. We report the bronchoscopic findings associated with a fatal case of H1N1 influenza A associated with co-infection with methicillin-resistant Staphylococcus aureus (MRSA) in a previously healthy child, which were more severe than those previously described as associated with seasonal influenza infection alone. The severity of the airway pathology seen on bronchoscopy in this patient may be due to a unique effect of the H1N1 influenza A virus or may be as a result of a destructive synergism between this virus and bacteria such as MRSA.

Topics: Anti-Bacterial Agents; Bronchoscopy; Child; Fatal Outcome; Female; Fibrinolytic Agents; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Lung; Meropenem; Methicillin-Resistant Staphylococcus aureus; Oseltamivir; Respiratory Distress Syndrome; Respiratory Insufficiency; Staphylococcal Infections; Thienamycins; Tissue Plasminogen Activator; Vancomycin

Topics: Abscess; Acetamides; Acute Disease; Adult; Anti-Bacterial Agents; Bacterial Toxins; Cellulitis; Drainage; Drug Therapy, Combination; Exotoxins; Fever; Humans; Iraq; Leg; Leukocidins; Linezolid; Magnetic Resonance Imaging; Male; Meropenem; Military Personnel; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We report a unique case of a toddler (the only one reported) successfully operated on for a medulla oblongata abscess and comment on the influence of neuroimaging modalities in the preoperative planning of the surgical approach.. We report a case of a 20-month-old child with a solitary medulla oblongata abscess. The abscess appeared to be in close proximity to the anterior medulla oblongata, but preoperative planning based on diffusion tensor imaging (DTI) tractography motivated us to try to remove this lesion through a midline suboccipital approach. The ventral medulla oblongata abscess was surgically removed via a telovelar approach. At the anterior wall of the 4th ventricle, a fenestration was made with pus release and evacuation of the cavity. The child was discharged 1 week later with an uneventful and full recovery.. Modern imaging modalities of the nervous system can be very helpful in preoperative planning. Functional visualization of the nervous system provided by modern imaging techniques, such as the DTI tractography, can alter the classic topographic concept of surgical approach. In the case presented, approaching an anterior medulla oblongata abscess based on DTI tractography data, through a suboccipital midline transventricular approach, proved to be an effective and safe technique.

Topics: Ampicillin; Anti-Bacterial Agents; Brain Abscess; Diffusion Tensor Imaging; Female; Humans; Infant; Medulla Oblongata; Meropenem; Neurosurgical Procedures; Staphylococcal Infections; Staphylococcus hominis; Thienamycins; Vancomycin

Ceftobiprole, a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) (P. Hebeisen et al., Antimicrob. Agents Chemother. 45:825-836, 2001), was evaluated in a subcutaneous skin infection model with Staphylococcus aureus Smith OC 4172 (methicillin-susceptible S. aureus [MSSA]), S. aureus OC 8525 (MRSA), Pseudomonas aeruginosa OC 4351 (having an inducible AmpC beta-lactamase), and P. aeruginosa OC 4354 (overproducing AmpC beta-lactamase). In the MSSA and MRSA infection models, ceftobiprole, administered as the prodrug ceftobiprole medocaril, was more effective in reducing CFU/g skin (P < 0.001) than were cefazolin, vancomycin, or linezolid based on the dose-response profiles. Skin lesion volumes in MSSA-infected animals treated with ceftobiprole were 19 to 29% lower than those for cefazolin-, vancomycin-, or linezolid-treated animals (P < 0.001). In MRSA infections, lesion size in ceftobiprole-treated mice was 34% less than that with cefazolin or linezolid treatment (P < 0.001). Against P. aeruginosa, ceftobiprole at similar doses was as effective as meropenem-cilastatin in reductions of CFU/g skin, despite 8- and 32-fold-lower MICs for meropenem; both treatments were more effective than was cefepime (P < 0.001) against the inducible and overproducing AmpC beta-lactamase strains of P. aeruginosa. Ceftobiprole was similar to meropenem-cilastatin and 47 to 54% more effective than cefepime (P < 0.01) in reducing the size of the lesion caused by either strain of P. aeruginosa in this study. These studies indicate that ceftobiprole is effective in reducing both bacterial load and lesion volume associated with infections due to MSSA, MRSA, and P. aeruginosa in this murine model of skin and soft tissue infection.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Bacterial Proteins; beta-Lactamases; Cephalosporins; Colony Count, Microbial; Dose-Response Relationship, Drug; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Half-Life; Immunocompromised Host; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Hairless; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Skin Diseases, Infectious; Staphylococcal Infections; Staphylococcus aureus

Clostridium difficile (CD) infection is almost always confined to the colon causing a spectrum of illness ranging from diarrhoea to fulminant colitis. CD infection of the small intestine has been described but the identification of CD toxin in the stoma effluent of a patient with an end ileostomy is rare. We describe a 91-year-old woman, with a history of proctocolectomy for ulcerative colitis, presenting with profuse ileostomy diarrhoea after a course of antibiotics. Ileostomy effluent was positive for CD toxin but the patient died despite appropriate treatment. This suggests that the small intestine is susceptible to CD infection in antibiotic-treated patients many years after a colectomy. CD enteritis should be considered in all patients with increased ileostomy diarrhoea despite the absence of a colon.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Colectomy; Colitis, Ulcerative; Enterocolitis, Pseudomembranous; Fatal Outcome; Female; Humans; Ileostomy; Infusions, Intravenous; Intestine, Small; Meropenem; Postoperative Complications; Staphylococcal Infections; Thienamycins

AFN-1252, a potent inhibitor of enoyl-acyl carrier protein reductase (FabI), inhibited all clinical isolates of Staphylococcus aureus (n = 502) and Staphylococcus epidermidis (n = 51) tested, including methicillin (meticillin)-resistant isolates, at concentrations of 4 microg/ml) against clinical isolates of Streptococcus pneumoniae, beta-hemolytic streptococci, Enterococcus spp., Enterobacteriaceae, nonfermentative gram-negative bacilli, and Moraxella catarrhalis. These data support the continued development of AFN-1252 for the treatment of patients with resistant staphylococcal infections.

Topics: Anti-Bacterial Agents; Benzofurans; Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); Enterobacteriaceae; Enterococcus; Microbial Sensitivity Tests; Moraxella catarrhalis; Pyrones; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus; Staphylococcus epidermidis; Streptococcus pneumoniae

Topics: Anti-Bacterial Agents; Back Pain; Cefepime; Cephalosporins; Diagnosis, Differential; Drainage; Epidural Abscess; Fever; Humans; Male; Meropenem; Middle Aged; Myelography; Paresis; Prognosis; Radiography, Abdominal; Shivering; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Time Factors; Tomography, X-Ray Computed

Two investigational anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) beta-lactams, ceftaroline (a cephalosporin) and ME1036 (a carbapenem), were subjected to susceptibility testing by reference broth microdilution methods using 152 strains of community-acquired MRSA from the United States (47 medical centers). Ceftaroline and ME1036 were 64- and >128-fold more potent than ceftriaxone, respectively. All isolates had the Panton-Valentine leukocidin genes and staphylococcal cassette chromosome mec type IV, while 67.8% of isolates displayed pulsed-field gel electrophoresis clonal type USA300-0114.

Topics: Anti-Bacterial Agents; beta-Lactams; Carbapenems; Ceftaroline; Cephalosporins; Community-Acquired Infections; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus; United States

Since its first isolation in 1997, vancomycin-intermediate Staphylococcus aureus (VISA) has been a clinical concern because it may lead to treatment failure. Up to the present, there were two reports of clinical VISA cases in Korea. We now report two additional cases of VISA with the minimum inhibitory concentration (MIC) of 4 microg/mL. The first patient was a 59 yr-old man who had undergone total hip replacement arthroplasty in 1999 due to avascular necrosis of femur heads. He had recurrent episodes of infected hip caused by methicillin-resistant Staphylococcus aureus (MRSA) and was treated with vancomycin. He underwent replacement operation of prosthesis. Cultures of joint fluid and joint tissue grew S. aureus. Vancomycin MIC as determined by a broth microdilution method was 4 microg/mL for the both isolates. The patient was treated with high enough doses of vancomycin to maintain serum trough concentrations at 20-25 microg/mL for 52 days and was discharged. The second patient was a 57 yr-old man with diabetes. He lost consciousness from drinking. After recovery of consciousness, he was diagnosed with aspiration pneumonia. MRSA and Acinetobacter baumannii were cultured from sputum and the patient was treated with vancomycin and meropenem. During hospitalization, bed sores developed in his ankle and back. A wound culture from the sore grew S. aureus with vancomycin MIC of 4 microg/mL. Since infection was localized, systemic antibiotics did not seem necessary, and the patient was transferred to another hospital for isolation and management.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Humans; Joints; Male; Meropenem; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Pressure Ulcer; Staphylococcal Infections; Thienamycins; Vancomycin; Vancomycin Resistance

The Meropenem Yearly Susceptibility Test Information Collection Program is a 9-year-old antimicrobial resistance surveillance network of more than 100 medical centers worldwide, including 15 sites in the United States (US) that monitors the susceptibility of Gram-negative and Gram-positive bacterial pathogens especially to carbapenems. In 2005, the antimicrobial activity of 11 broad-spectrum agents was assessed against 2910 bacterial isolates (2493 Gram-negative and 417 staphylococci) submitted from the US medical centers to a reference laboratory using Clinical and Laboratory Standards Institute susceptibility testing methods and interpretative criteria. Meropenem continued to demonstrate 1) high potency with MIC(90) values 4- to 16-fold lower than imipenem against the Enterobacteriaceae, 2) equal activity against Pseudomonas aeruginosa, 3) 2-fold less activity compared with imipenem against Acinetobacter spp., and 4) 4- to 8-fold less activity compared with imipenem against the oxacillin-susceptible staphylococci. The wide spectrum of activity for carbapenems against Enterobacteriaceae (1657 strains) was confirmed by the overall rank order by percentage susceptibility at breakpoint criteria: imipenem (98.9%) > meropenem (98.7%) > cefepime (97.6%) > piperacillin/tazobactam (92.0%) > ceftriaxone (91.2%) > aztreonam (90.6%) > gentamicin = tobramycin (90.5%) > ceftazidime (90.4%) > levofloxacin (84.9%) > ciprofloxacin (83.9%). Against Acinetobacter spp. isolates, only tobramycin (92.0% susceptible) and carbapenems (92.0-85.6%) exhibited acceptable levels of activity. A continued increase in the resistance rate for both ciprofloxacin and levofloxacin was observed with highest rates found among indole-positive Proteae species (36.5-33.3%) and Escherichia coli (21.6-20.4%) isolates, some documented by molecular typing methods as clonally related. Ongoing surveillance of meropenem and other broad-spectrum antimicrobial agents appears warranted to monitor the potency and spectrum of activity against indicated Gram-negative and-positive pathogens causing serious infections in the hospital setting, and to detect the emergence of new or novel resistance mechanisms that could compromise clinical utility (serine and metallo-carbapenemases).

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Longitudinal Studies; Meropenem; Microbial Sensitivity Tests; Population Surveillance; Staphylococcal Infections; Staphylococcus; Thienamycins; United States

Within last 15 years, analyzing patterns of etiology and resistance in organisms causing neuroinfections, emergence of resistance has been observed in Slovakia in S. haemolyticus to teicoplanin (11%), Ps. aeruginosa and A. baumannii to meropenem (20%) and Candida spp. (non-albicans Candida spp.) to fluconazol (20%). There are no new antibiotics against carbapenem resistant Ps. aeruginosa and Acinetobacter baumannii.

Topics: Anti-Infective Agents; Brain Diseases; Candidiasis; Cross Infection; Drug Resistance, Microbial; Fluconazole; Humans; Meningitis; Meropenem; Pseudomonas Infections; Staphylococcal Infections; Teicoplanin; Thienamycins

Nosocomial infections after spinal surgery are relatively uncommon but potentially serious. The goal of diagnostic evaluation is to determine the extent of infection and identify the microorganism involved. Neuroimaging provides accurate information on correct topography, localization and propagation of the infection. Microbiological data are able to give aetiological causes. In this patient with severe, chronic polymicrobial spine infection with epidural abscess and CSF fistula due to multidrug-resistant organisms, the cure was achieved with long-term antimicrobial specific therapy with quinupristin-dalfopristin (50 days) and linezolid (100 days) with mild side effects. This positive result was due to combined medical and surgical treatment.

Topics: Acetamides; Anti-Bacterial Agents; Bacteria; Cerebrospinal Fluid; Combined Modality Therapy; Cross Infection; Curettage; Device Removal; Discitis; Epidural Abscess; Female; Fistula; Fluconazole; Fungi; Humans; Internal Fixators; Laminectomy; Linezolid; Lumbar Vertebrae; Meropenem; Methicillin Resistance; Middle Aged; Osteomyelitis; Oxazolidinones; Parkinson Disease; Prosthesis-Related Infections; Reoperation; Skin Diseases; Spinal Diseases; Spinal Stenosis; Staphylococcal Infections; Thienamycins; Virginiamycin

The coagulase-negative bacterial species Staphylococcus sciuri is widely distributed in the natural environment. Although principally found in animals, S. sciuri is occasionally isolated from human samples. In this paper, S. sciuri bacteremia which was associated with an indwelling catheter of a patient with acute myeloid leukemia (AML) and neutropenia was presented. An empirical intravenous antibiotic therapy (meropenem, vancomycin) was initiated with the preliminary diagnosis of febrile neutropenia and catheter infection. The catalase and oxidase positive, tube coagulase negative strain isolated from three of the concurrent blood cultures and intravenous catheter culture has been identified as S. sciuri. The isolate was found resistant to penicilin and oxacilline. This case has emphasized the importance of identification of coagulase-negative staphylococci isolated from the cultures of patients with haematological malignancy.

Topics: Anti-Bacterial Agents; Bacteremia; Catheters, Indwelling; Drug Resistance, Bacterial; Female; Humans; Leukemia, Myeloid, Acute; Meropenem; Middle Aged; Neutropenia; Oxacillin; Penicillin Resistance; Staphylococcal Infections; Staphylococcus; Thienamycins; Vancomycin

The bactericidal effect of some antibiotic and antineoplastic agents commonly used in clinical practice was investigated to analyse whether the combinations act synergistically, have indifferent or antagonistic antibacterial effects compared to the effect of the antibiotics alone.. The rate of killing of meropenem, ceftazidime and tobramycin was studied against six different strains of Staphylococcus aureus and Escherichia coli, and the results were compared to the rate of killing of the antibiotics in combination with the cytostatic drugs doxorubicin, etoposide and 5-fluorouracil (5-FU).. Tobramycin showed synergy against two strains of S. aureus after 3 h in the presence of 5-FU and against one strain of S. aureus in the presence of doxorubicin. Meropenem induced an antagonistic bactericidal effect against one isolate of S. aureus after 24 h. Ceftazidime expressed an indifferent bactericidal effect together with the cytostatic agents. The antineoplastic agents had no impact on the bacterial killing of any of the antibiotics against E. coli.. Tobramycin expressed a significantly better bactericidal effect against S. aureus after 3 h in the presence of doxorubicin and 5-FU than tobramycin alone. Meropenem expressed antagonism against one clinical strain of S. aureus, but the cytostatic drugs did not affect the killing of other strains tested. Ceftazidime expressed indifferent bactericidal activity together with the antineoplastic agents.

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Ceftazidime; Cephalosporins; Doxorubicin; Drug Interactions; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Etoposide; Fluorouracil; Meropenem; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Tobramycin

The efficacies of meropenem (MPM) and cloxacillin (CLC) against two Staphylococcus aureus strains were established in vitro. A pharmacodynamic model equation, based on the concept that the killing rate depends on concentration and time, was fitted to the numbers of CFU. The parameters of the equation are maximum killing rate, time point of maximum killing, and 50% effective concentration (EC50). The EC50s for the two strains were 0.047 and 0.040 mg/liter, respectively, for MPM and 0.105 and 0.121 mg/liter, respectively, for CLC. Calculated values of the parameters were used to predict the numbers of CFU at exponentially decreasing concentrations in vitro as well as in an experimental infection model. The prediction for in vitro conditions gave a satisfactory fit (R2, between 0.862 and 0.894). In vivo the numbers were predicted with the assumption that killing rate in vivo is proportional to that in vitro (R2, between 0.731 and 0.973). The proportionality factor ranged between 0.23 and 0.42; this variation was due mainly to covariation with growth rates in control animals, without other significant differences between antibiotics or strains.

Topics: Animals; Anti-Bacterial Agents; Cloxacillin; Colony Count, Microbial; Female; Meropenem; Mice; Microbial Sensitivity Tests; Protein Binding; Staphylococcal Infections; Staphylococcus aureus; Thienamycins

The synthesis and in vitro antibacterial activity of a novel series of 2-alkoxymethyl-4-pyrrolidinylthio-1 beta-methyl carbapenems are described. As a result of these studies, we discovered that FR27743 (19j) containing a novel 2-fluoroethoxymethyl substituent possesses a broad spectrum of antibacterial activity against both Gram-positive and Gram-negative organisms, including Pseudomonas aeruginosa. Furthermore, FR27743 exhibited excellent stability against renal dehydropeptidase-I (DHP-I), good urinary recovery, and superior in vivo activity compared to that for Meropenem against several systemic infections.

Topics: Animals; Carbapenems; Dipeptidases; Drug Stability; Male; Meropenem; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Pseudomonas Infections; Rats; Staphylococcal Infections; Thienamycins; Urine

Several pharmacodynamic parameters are being studied and applied to the design of dosage regimens. The thigh infection model in neutropenic mice has been used in this study to investigate the in vivo postantibiotic effect (PAE) of meropenem against S. aureus, E. coli and P. aeruginosa. The sub-minimum inhibitory concentration (sub-MIC) postantibiotic effect (PA SME) of 1/2, 1/4 and 1/8 x MIC was also determined in vitro on S. aureus and E. coli after pre-exposure of these microorganisms to 10 x MIC of meropenem. The in vitro PAE was also determined. In vivo killing curves using 2 different short dosage regimens were also studied to relate the lethal effect to the time that serum levels were above the MIC. No significant in vivo and in vitro PAEs were observed. The PA SMEs were higher for S. aureus than for E. coli. The 2 short dosage regimens, in vivo, were equally effective in killing S. aureus, but not E. coli. These results suggest that the pharmacodynamics of meropenem on Gram-negative strains may need further study to elucidate the mechanisms and characteristics of these parameters. On the other hand, we need to standardize a reliable in vitro method to monitor regrowth with a good correlation with the in vivo conditions.

Topics: Animals; Drug Evaluation, Preclinical; Drug Resistance, Microbial; Escherichia coli; Escherichia coli Infections; Female; In Vitro Techniques; Meropenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Thienamycins

We studied a newly developed carbapenem, meropenem (MEPM), and obtained the following results. 1. Pharmacokinetics of MEPM in pediatrics was examined in 3 patients. MEPM was injected intravenously at a dose of 16-22 mg/kg by drip infusion for 30 minutes, and its concentrations in serum and urine were determined using bioassay. The average peak value of serum levels of MEPM was 38.4 micrograms/ml and T1/2 beta of MEPM was 1.26 hours. The urinary recovery rate for the first 6 hours after administration was 65.6%. 2. Clinical evaluations of MEPM in pediatrics were done in 14 patients with ages ranging, 1 month to 14 years, with various bacterial infections. Excellent or good clinical responses were observed in all patients, and bacteriological eradication were obtained in 7 out of 8 cases. No serious side effects were observed in any cases, but 2 showed mild and transient GOT, GPT elevations.

Topics: Adolescent; Bacterial Infections; Child; Child, Preschool; Citrobacter freundii; Enterobacteriaceae Infections; Female; Humans; Infant; Male; Meropenem; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus epidermidis; Thienamycins

Forty-five children were treated with meropenem (MEPM) and the clinical efficacy and side effects were evaluated. The ages of the patients ranged from 1 month to 9 years and their body weights from 5.2 to 25 kg. Doses given were 17.2-45.5 mg/kg every 6 to 8 hours for 2 to 24.5 days. Those patients who responded to the MEPM treatment included 15 children with pneumonia, 7 with pharyngitis, 3 with cervical lymphadenitis, 3 with cellulitis, 10 with urinary tract infections and 4 with other infections. Among 42 children, the results were excellent in 29, good in 12 and fair in 1. The drug was well tolerated, although slightly elevated serum concentrations of transaminases occurred in 5 patients, eosinophilia in 2 patients, and neutropenia in 1 patient among 45 patients examined. The pharmacokinetic studies on MEPM were done in 6 patients. Their ages ranged from 2 to 9 years and body weights from 14.5 to 23.2 kg. In 4 patients, plasma concentrations at the end of 30 minutes drip infusion of 20 mg/kg were 29.28 +/- 10.29 micrograms/ml and those 3 hours later were 0.49 +/- 0.26 micrograms/ml. Serum elimination half-lives of the drug were 0.66 +/- 0.12 hours in these patients. Excretion rates of this drug into urine in the first 6 hours after initiation of drug administration were 53 and 40% in 2 of these patients. In 2 patients with 35 and 44 mg/kg of drug administration, plasma concentrations were higher than those given 20 mg/kg of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bacterial Infections; Bifidobacterium; Child; Child, Preschool; Enterobacteriaceae; Escherichia coli Infections; Feces; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Meropenem; Staphylococcal Infections; Streptococcal Infections; Streptococcus pyogenes; Thienamycins

We studied the clinical efficacy of meropenem (SM-7338, MEPM), a new parenteral carbapenem beta-lactam antibiotic, in pediatric field. Thirteen patients with 2 months to 8 years and 8 months of ages, with acute infectious diseases were administered with doses at 39.3 to 76.7 mg/kg/day of MEPM intravenously. The diagnoses consisted of 7 respiratory tract infections, 1 sepsis, 2 orbital cellulitis, 1 parotid abscess, 1 lymphadenitis and 1 pyoderma. The clinical efficacy rate was 84.6% (11/13), and the bacteriological eradication rate was 71.4% (5/7). Clinical laboratory examinations revealed 1 patient with eosinophilia and another with anemia. No other side effects attributable to this drug were observed. It appears that MEPM is a useful antibiotic for moderate to severe acute bacterial infections in children.

Topics: Bacterial Infections; Child; Child, Preschool; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Meropenem; Moraxella catarrhalis; Neisseriaceae Infections; Pneumococcal Infections; Respiratory Tract Infections; Staphylococcal Infections; Thienamycins

Bacteriological and clinical studies have been performed on meropenem (MEPM, SM-7338), a newly developed carbapenem antibiotic, in the pediatric field. 1. Antibacterial activities of MEPM against 24 clinical isolates were determined. MEPM showed excellent activity against Gram-positive bacteria including Staphylococcus aureus and Gram-negative bacteria, especially Escherichia coli and Branhamella catarrhalis. Against Haemophilus influenzae, MEPM had a higher activity than imipenem and flomoxef, but had a lower activity than piperacillin and cefoperazone. 2. Clinical efficacies of MEPM were evaluated in 32 cases with bacterial infections. A poor efficacy was observed in 1 patient with phlegmon but excellent or good efficacies were obtained in other 31 patients with tonsillitis (1), pneumonia (17), UTI (12), or SSSS (1). The overall efficacy rate was 96.9%. All strains except 1 of S. aureus were eradicated by the administration of MEPM, and a high eradication rate of 95.8% (23 out of 24 strains) was obtained. 3. No side effects were observed in 35 evaluated cases. As abnormal laboratory test results, elevated GOT, elevated GPT, eosinophilia and neutropenia were noted in 4, 4, 4 and 2 patients, respectively. 4. Influences on blood coagulation parameters were studied. PIVKA II was elevated upon administration of MEPM in some cases, but no changes in ATT, TT, HPT or Fbg were observed during the treatment. Based on the above results, it has been concluded that MEPM is a safe and effective drug to use in the treatment of pediatric infections. The usual recommended dosage and administration should be 10 to 20 mg/kg of MEPM at a time, using intravenous drip infusion, 3 times a day.

Topics: Adolescent; Bacterial Infections; Child; Child, Preschool; Escherichia coli Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Meropenem; Moraxella catarrhalis; Neisseriaceae Infections; Pneumococcal Infections; Staphylococcal Infections; Streptococcal Infections; Streptococcus pyogenes; Thienamycins

The transferability of meropenem (MEPM) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus. The mean serum concentration was 93.1 +/- 13.5 micrograms/ml at 15 minutes after intravenous administration of MEPM at a dose level of 100 mg/kg. The mean concentration in CSF was maximum at 15 minutes after administration at 4.42 +/- 2.24 micrograms/ml. Pharmacokinetic parameters calculated from these values were as follows: Cmax (CSF/serum) 4.75%, AUC (CSF/serum) 10.4% between 15 and 60 minutes, 13.9% between 15 and 120 minutes and 15.7% between 15 and 180 minutes, T 1/2 for MEPM in CSF: 50.9 minutes, T 1/2 (CSF/serum): 2.19. In comparison to those of imipenem which were obtained in the same way, the transferability of MEPM was similar and in consideration of the antimicrobial potency against the main pathogens of meningitis, it appears worth-while of running clinical trials for this drug.

Topics: Animals; Biological Transport; Half-Life; Meningitis; Meropenem; Rabbits; Staphylococcal Infections; Staphylococcus aureus; Thienamycins