meropenem and Haemophilus-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

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

A 59-year-old man presented with a three-month history of back pain, and enhanced computed tomography demonstrated an acutely expanding aneurysm of the descending thoracic aorta with slight erosion of the corresponding vertebrae. Because of suspected infectious or inflammatory etiology, he was managed with a combination of emergency aortic repair using prosthetic graft with omental flap and antibiotic chemotherapy. Haemophilus influenzae was identified from perioperative specimens and the postoperative course was uneventful.

Topics: Aneurysm, Infected; Anti-Bacterial Agents; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Blood Vessel Prosthesis Implantation; Emergencies; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Meropenem; Middle Aged; Surgical Flaps; Thienamycins; Treatment Outcome

By Etest determination of the susceptibilities of 229 Haemophilus influenzae strains isolated in Korea to 10 antibiotics, the isolates were found to be antibiotic nonsusceptible in the following order: ampicillin (58.1%), trimethoprim-sulfamethoxazole (52%), cefaclor (41.1%), clarithromycin (25.8%), chloramphenicol (14.0%), amoxicillin-clavulanic acid (13.5%), meropenem (11.7%), cefixime (10.9%), cefuroxime (9.2%), and levofloxacin (1.3%). The prevalences of each resistance class were 23.6% for beta-lactamase-negative ampicillin-susceptible (BLNAS) strains; 37.6% for strains with the TEM-1 type beta-lactamase gene; 1.3% for strains with the ROB-1 type beta-lactamase gene; 29.3% for the beta-lactamase-negative ampicillin-resistant (BLNAR) strains with a mutation in the ftsI gene, which encodes PBP 3; and 8.3% for beta-lactamase-positive amoxicillin-clavulanate-resistant (BLPACR) strains, which showed both resistance mechanisms (i.e., a beta-lactamase gene and a mutation in the ftsI gene). The MIC50s of all beta-lactams, including cephem and meropenem agents, for the BLNAR strains were two to three times higher than those for the BLNAS strains. This study confirms that the prevalence of BLNAR and BLPACR strains is relatively high and for the first time confirms the presence of H. influenzae strains carrying blaROB-1 in Korea. Even though mutations in another gene(s) might be involved in beta-lactam resistance, these results suggest that mutations in the ftsI gene are important for the development of resistance to beta-lactams in H. influenzae strains in Korea.

Topics: Ampicillin Resistance; beta-Lactamases; Drug Resistance, Bacterial; Genes, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Korea; Microbial Sensitivity Tests; Mutation; Penicillin-Binding Proteins; Species Specificity

Equivalent MIC breakpoints to detect beta-lactamase negative ampicillin resistant Haemophilus influenzae (BLNAR) were controversial. We studied the relationship of drug resistance with gene alterations in 74 clinical isolates of H. influenzae. Out of 74 isolates, 26 showed MIC of ampicillin (ABPC) > or = 1 microg/ml. All isolates, except one, with MIC of ABPC > or = 4 microg/ml were found to produce beta-lactamase, while all 19 isolates with MIC of ABPC at 1 or 2 microg/ml were non-producing. Twenty-six ABPC resistant isolates were subjected to the analysis of genes involved in the drug resistance such as pbp3-1 pbp3-2, and TEM by the Haemophilus influenzae gene detection kit (Wakunaga Pharmaceutical Co., Ltd.) according to the supplier's instructions. Three (21.4%) of 14 beta-lactamase non-producing isolates with ABPC-MIC of 1 microg/ml had mutations of pbp3-1 gene, while all 5 non-producing isolates with ABPC-MIC of 2 microg/ml showed mutations of both pbp3-1 and pbp3-2 genes. Accordingly, it seems appropriate to set ABPC-MIC > or = 2 microg/ml for detection of BLNAR. In this study, six (8.1%) of 74 isolates were found to be BLNAR, and all of these six isolates were derived from patients of 5 year-old or younger.

Topics: Ampicillin Resistance; Anti-Bacterial Agents; beta-Lactamases; Child, Preschool; Drug Resistance, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Molecular Epidemiology; Prevalence; Reagent Kits, Diagnostic; Thienamycins

The in vitro activity of ampicillin, cefotaxime, meropenem, panipenem, imipenem and biapenem was assayed using ampicillin-susceptible, beta-lactamase-positive and beta-lactamase-negative ampicillin-resistant (BLNAR) Haemophilus influenzae isolated recently in Japan. Against ampicillin-susceptible isolates, cefotaxime was the most potent (MIC(90) 0.016 mg/mL). Both cefotaxime and meropenem (MIC(90) of both, 0.5 mg/L) were the most potent against beta-lactamase-positive isolates. Against BLNAR isolates, meropenem (MIC(90) 0.5 mg/L) was the most potent. In murine bronchopneumonia caused by ampicillin-susceptible and BLNAR H. influenzae, cefotaxime showed the best efficacy, followed by meropenem. Our results indicate that meropenem could be a useful intravenous agent for infections caused by H. influenzae, including BLNAR strains.

Topics: Ampicillin Resistance; Animals; Anti-Bacterial Agents; beta-Lactamases; Bronchopneumonia; Haemophilus Infections; Haemophilus influenzae; Humans; Meropenem; Mice; 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

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

Meropenem, a new parenteral carbapenem demonstrated increased activity as compared to imipenem against 336 strains of Neisseria gonorrhoeae, 119 strains of Haemophilus influenzae, and 110 strains of H. ducreyi. Neither carbapenem was affected by the beta-lactamase activity of the organisms tested. Ceftriaxone and ciprofloxacin demonstrated activity superior to that of both carbapenems while the activity of ceftazidime was similar to that of meropenem.

Topics: Anti-Bacterial Agents; Canada; Carbapenems; Gonorrhea; Haemophilus ducreyi; Haemophilus Infections; Haemophilus influenzae; Humans; Kenya; Meropenem; Microbial Sensitivity Tests; Neisseria gonorrhoeae; Thienamycins