meropenem and Pneumococcal-Infections

Meropenem administered as a single iv 3 g dose once every 24 h was used to treat nine ambulatory patients with infective exacerbations of bronchiectasis. Serum meropenem concentrations were measured before dosing and at 30 min after each 30 min infusion. Mean pre-dose concentrations were <0.1 mg/L and mean post-dose concentrations 93.9 +/- 29.5 mg/L (95% confidence interval (CI) 86. 2-101.6, n = 59). A pathogen was cultured from sputum in six patients and eradicated (<100 cfu/g sputum) in all but one by day 6 of therapy. Previous work on animals has shown that a bacteriostatic effect is seen with meropenem when t > MIC is greater than 20-30% of the dose interval. In these nine patients, this could be achieved and was associated with successful outcome for pathogens for which MICs are

Topics: Aged; Bronchiectasis; Female; Haemophilus Infections; Haemophilus influenzae; Half-Life; Humans; Male; Meropenem; Middle Aged; Pneumococcal Infections; Pseudomonas Infections; Respiratory Tract Infections; Thienamycins

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Genomics; Humans; Japan; Macrolides; Meropenem; Microbial Sensitivity Tests; Pneumococcal Infections; Serogroup; Serotyping; Spain; Streptococcus pneumoniae; Taiwan

After the introduction of pneumococcal conjugate vaccines, the incidence of pneumococcal infections due to meropenem-resistant serotype 15A-ST63 strains increased in Japan. By using whole-genome sequencing and comparing sequences with those of clones from the United Kingdom, the United States, and Canada, we clarified the traits of the serotype 15A-ST63 clone. Our analysis revealed that the meropenem-resistant serotype 15A-ST63 strains from Japan originated from meropenem-susceptible strains from Japan. Recombination site prediction analysis showed that the meropenem-resistant strain-specific recombination regions included the pbp1a and pbp2b regions. A detailed analysis of the composition of these genes indicated that resistance seems to be caused by pbp1a recombination. The pbp1a gene in meropenem-resistant isolates was identical to that in multidrug (including meropenem)-resistant serotype 19A-ST320 pneumococci, which have spread in the United States. The global spread of pneumococci of this lineage is noteworthy because serotype 15A is not included in the currently used 13-valent pneumococcal conjugate vaccine.

Topics: Drug Resistance, Bacterial; Humans; Japan; Meropenem; Microbial Sensitivity Tests; Pneumococcal Infections; Serogroup; Streptococcus pneumoniae

Pneumococcal vaccines have reduced the incidences of Streptococcus pneumoniae infections among children and adults, but a relative increase in the prevalence of non-vaccine serotypes has been reported. To follow the changing epidemiology of pneumococcal diseases, capsular serotyping and antimicrobial susceptibility testing was performed on 534 pneumococcal isolates obtained from a hospital in Japan after routine immunization was launched, between October 2014 and May 2016. Serotype distributions and antimicrobial susceptibilities were evaluated among the total patient population, and were compared by age and sample groups and by serotype group, respectively. Serotypes targeted by the 13-valent pneumococcal conjugate vaccine (PCV13) were identified in 14.6%, 44.5%, and 40.2% of the samples from the <5, 5-64, and ≥65 year age groups, respectively. The 23-valent pneumococcal polysaccharide vaccine serotypes (PPSV23) were identified in 42.4%, 68.2%, and 63.1% of the samples, respectively; whereas non-PCV13 serotypes or non-PPSV serotypes (NVT) comprised 46.8% of all isolates. Among NVT, strain 35B was the most frequently isolated, followed by 15A, particularly in sputum samples collected from children <5 years old. Meanwhile, serotype 3, which is targeted by the PCV13 and PPSV23, was the most prevalent among patients aged ≥65 and 5-64 years. Antimicrobial susceptibility testing revealed that 88.9% and 81.0% of serotype 35B was non-susceptible to penicillin and meropenem, respectively, and 89.4% of 15A was non-susceptible to penicillin. Our data suggest rapid effects of pneumococcal vaccines and progression of serotype replacement. Besides invasive potential, the increased prevalence of non-vaccine serotypes with highly non-susceptible to penicillin was a concern. Continuous monitoring of pneumococcal serotypes and antimicrobial susceptibility is necessary for developing optimal preventive strategies.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Carrier State; Child; Female; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Immunization Programs; Incidence; Japan; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Prevalence; Serogroup; Serotyping; Streptococcus pneumoniae; Thienamycins; Vaccination; Young Adult

In Japan, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2010. PCV13 has replaced PCV7 since November 2013.. The effectiveness of PCV7 in protecting against invasive pneumococcal disease (IPD) in children aged <5 years was evaluated in a nationwide active population-based surveillance of IPD in 2008-2013 in 10 prefectures in Japan.. 1181 cases were identified; 711 pneumococcal strains were analyzed for serotyping and antimicrobial resistance. Compared with the baseline IPD incidence (25.0 per 100,000), a 98% decline in IPD caused by PCV7 serotypes was found after the introduction of PCV7. This was partially offset by an increased incidence of IPD caused by PCV13 minus PCV7 and non-PCV13 serotypes, resulting in a 57% decline in overall IPD incidence. Absolute increases in the incidence rates of IPD caused by PCV13 minus PCV7 and non-PCV13 serotypes were 2.1 and 2.8 per 100,000 during the study period, respectively. The proportion of meropenem-nonsusceptible strains, especially with serotypes 19A and 15A, increased significantly after PCV7 introduction.. Our data confirmed a 98% decline in IPD incidence caused by PCV7 serotypes in children aged <5 years and serotype replacement after PCV7 introduction. This shows the importance of continuing surveillance of serotypes responsible for IPD and their antimicrobial resistance in Japan.

Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Female; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Infant; Japan; Male; Meropenem; Microbial Sensitivity Tests; Pneumococcal Infections; Population Surveillance; Prospective Studies; Serogroup; Streptococcus pneumoniae; Thienamycins

From February to December 20XX, penicillin-resistant Streptococcus pneumoniae (PRSP) showing MICs of 16-32 microg/mL to cefotaxime (CTX) and 4-8 microg/mL to meropenem (MEPM) were isolated from 6 patients hospitalized at the general hospital S (2 cases) and hospital A (4 cases), close to the hospital S. Five elderly patients among these six cases came from nursing care facilities or nursing care-related medical facilities. All elderly persons (mean age: 81.7 years) were diagnosed as having pneumonia at the time of admission and the problematic PRSP was isolated from sputum samples collected on admission. Notably, all of these PRSP isolates simultaneously showed high resistance to macrolide agents mediated by an erm (B) gene and to fluoroquinolone agents via mutations in the gyrA and parC genes. Eventually, they were identified as multidrug-resistant S. pneumoniae (MDRSP) with high resistance to many agents. The capsule type of all strains was serotype 19F and multilocus sequence typing (MLST) revealed that they belonged to clonal complex (CC) 7993, which has not been reported before. It was thus concluded that the MDRSP that had spread within the nursing facilities was transmitted to the general hospitals via the elderly inpatients with pneumonia caused by these agents. Although one case finally had a poor outcome, the pneumococcal infection was not the direct trigger of the event. The current ratio of MDRSP is concluded to be very low. However, general hospitals that accept patients for therapeutic purposes from nursing-care facilities have to share epidemiological information in a timely manner with the nursing homes to prevent nosocomial infections.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Meropenem; Pneumococcal Infections; Skilled Nursing Facilities; Streptococcus pneumoniae; Thienamycins

Macrolide resistance in Streptococcus pneumoniae has emerged as an important clinical problem worldwide over the past decade. The aim of this study was to analyze the phenotypes (serotype and antibiotic susceptibility), genotypes (multilocus sequence type [MLST] and antibiotic resistance gene/transposon profiles) among the 31% (102/328) of invasive isolates from children in New South Wales, Australia, in 2005 that were resistant to erythromycin. Three serotypes--19F (47 isolates [46%]), 14 (27 isolates [26%]), and 6B (12 isolates [12%])--accounted for 86 (84%) of these 102 isolates. Seventy four (73%) isolates had the macrolide-lincosamide-streptogramin B (MLS(B)) resistance phenotype and carried Tn916 transposons (most commonly Tn6002); of these, 73 (99%) contained the erythromycin ribosomal methylase gene [erm(B)], 34 (47%) also carried the macrolide efflux gene [mef(E)], and 41 (55%) belonged to serotype 19F. Of 28 (27%) isolates with the M phenotype, 22 (79%) carried mef(A), including 16 (57%) belonging to serotype 14, and only six (19%) carried Tn916 transposons. Most (84%) isolates which contained mef also contained one of the msr(A) homologues, mel or msr(D); 38 of 40 (95%) isolates with mef(E) (on mega) carried mel, and of 28 (39%) isolates with mef(A), 10 (39%) carried mel and another 11(39%) carried msr(D), on Tn1207.1. Two predominant macrolide-resistant S. pneumoniae clonal clusters (CCs) were identified in this population. CC-271 contained 44% of isolates, most of which belonged to serotype 19F, had the MLS(B) phenotype, were multidrug resistant, and carried transposons of the Tn916 family; CC-15 contained 23% of isolates, most of which were serotype 14, had the M phenotype, and carried mef(A) on Tn1207.1. Erythromycin resistance among S. pneumoniae isolates in New South Wales is mainly due to the dissemination of multidrug-resistant S. pneumoniae strains or horizontal spread of the Tn916 family of transposons.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Child, Preschool; DNA Transposable Elements; Drug Resistance, Bacterial; Erythromycin; Genotype; Humans; Macrolides; Microbial Sensitivity Tests; New South Wales; Pneumococcal Infections; Serotyping; Streptococcus pneumoniae

Increasing pneumococcal resistance to extended-spectrum cephalosporins warrants the search for novel agents with activity against such resistant strains. Ceftaroline, a parenteral cephalosporin currently in phase 3 clinical development, has demonstrated potent in vitro activity against resistant gram-positive organisms, including penicillin-resistant Streptococcus pneumoniae. In this study, the activity of ceftaroline was evaluated against highly cefotaxime-resistant isolates of pneumococci from the Active Bacterial Core surveillance program of the Centers for Disease Control and Prevention and against laboratory-derived cephalosporin-resistant mutants of S. pneumoniae. The MICs of ceftaroline and comparators were determined by broth microdilution. In total, 120 U.S. isolates of cefotaxime-resistant (MIC > or = 4 microg/ml) S. pneumoniae were tested along with 18 laboratory-derived R6 strains with known penicillin-binding protein (PBP) mutations. Clinical isolates were characterized by multilocus sequence typing, and the DNAs of selected isolates were sequenced to identify mutations affecting pbp genes. Ceftaroline (MIC(90) = 0.5 microg/ml) had greater in vitro activity than penicillin, cefotaxime, or ceftriaxone (MIC(90) = 8 microg/ml for all comparators) against the set of highly cephalosporin-resistant clinical isolates of S. pneumoniae. Ceftaroline was also more active against the defined R6 PBP mutant strains, which suggests that ceftaroline can overcome common mechanisms of PBP-mediated cephalosporin resistance. These data indicate that ceftaroline has significant potency against S. pneumoniae strains resistant to existing parenteral cephalosporins and support its continued development for the treatment of infections caused by resistant S. pneumoniae strains.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Bacterial Typing Techniques; Ceftaroline; Cephalosporins; DNA, Bacterial; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Penicillin-Binding Proteins; Pneumococcal Infections; Streptococcus pneumoniae

Broth microdilution was used to determine the MICs of AR-709 and comparator antimicrobial agents for 224 invasive multidrug-resistant isolates of Streptococcus pneumoniae. AR-709 was highly active, with a MIC 50 of 0.25 microg/ml, a MIC 90 of 0.5 microg/ml, and a range of

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Indoles; Microbial Sensitivity Tests; North America; Pneumococcal Infections; Pyrimidines; Streptococcus pneumoniae; Tetrahydrofolate Dehydrogenase

We report a rare case of multiple vertebral osteomyelitis due to Streptococcus pneumoniae. A 73-year-old man admitted for back pain and a low-grade fever was found in laboratory studies to have severe leukocytosis and increased C-reactive protein, but neither computed tomography (CT) nor vertebral magnetic resonance imaging (MRI) clarified the cause of infection in the painful hip lesion, and paralysis developed. in the left leg MRI eventually indicated a vertebral abscess involving multiple lesions at C4-7 and L4-5. We had started antibiotics before blood culture clarified Streptocccus pneumonaie, and antibiotics acted more effectively thereafter. The clinical course was good, little paralysis remained.

Topics: Aged; Anti-Bacterial Agents; beta-Alanine; Cervical Vertebrae; Clindamycin; Drug Therapy, Combination; Fosfomycin; Humans; Lumbar Vertebrae; Male; Meropenem; Osteomyelitis; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae; Thienamycins; Treatment Outcome

A collection of 307 pneumococcal isolates form 84 children and 223 adults admitted to Siriraj Hospital were separated into two groups, penicillin-susceptible (PSSP) and penicillin-nonsusceptible (PNSP). Each group was tested for susceptibilities to 12 drugs (cefuroxime, amoxicillin, chloramphenicol, tetracycline, cefotaxime, ceftriaxone, imipenem, meropenem, ciprofloxacin, ofloxacin, erythromycin and co-trimoxazole). PSSP were susceptible to cefuroxime (87.5%), amoxicillin (100%), chloramphenicol (84.7%), tetracycline (45.8%), cefotaxime (99%), ceftriaxone (99%), imipenem (99%), meropenem (100%), ciprofloxacin (76%), ofloxacin (99%), erythromycin (94.8%) and co-trimoxazole (61.5%). PNSP were resistant to most drugs, except for amoxicillin (99%), ofloxacin (99%) and ciprofloxacin (86.3%). Twenty-two pneumococcal isolates belonging to the three most common serotypes (6, 19, 23) were randomly selected for studies of the pbp2b gene with RFLP. There were 7 distinct pbp2b RFLP patterns. RFLP pattern 1 was the most predominant resistant pattern. The RFLP pattern 2 was found only in PSSP.

Topics: Adolescent; Adult; Aminoacyltransferases; Child; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Genotype; Humans; Imipenem; Meropenem; Middle Aged; Penicillin-Binding Proteins; Penicillins; Pneumococcal Infections; Polymerase Chain Reaction; Streptococcus pneumoniae; Thailand; Thienamycins

We investigated pneumococcal susceptibility to meropenem in isolates from a tertiary children's hospital where pneumococci are commonly resistant to penicillin and cefotaxime.. From July 1998 to August 1999, meropenem susceptibilities were determined by E-test for all Streptococcus pneumoniae isolates from blood or cerebrospinal fluid and for penicillin-nonsusceptible pneumococcal isolates from other sites.. Isolates that were penicillin-susceptible or penicillin-intermediate were all susceptible to meropenem. Of 29 penicillin-resistant isolates, 27 were nonsusceptible to meropenem (13 intermediate, 14 resistant). Cefotaxime-susceptible isolates were all susceptible to meropenem. Of 11 cefotaxime-intermediate isolates, 10 were nonsusceptible to meropenem (9 intermediate, 1 resistant). Of 20 cefotaxime-resistant isolates, 17 were nonsusceptible to meropenem (4 intermediate, 13 resistant).. Meropenem resistance is common among pneumococci with decreased susceptibility to penicillin or cefotaxime. The role of this agent in the treatment of invasive infections caused by pneumococci that are resistant to penicillin and cefotaxime may be limited.

Topics: beta-Lactam Resistance; Child; Hospitals, Pediatric; Humans; Meropenem; Microbial Sensitivity Tests; Pneumococcal Infections; Streptococcus pneumoniae; Tennessee; 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

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