meropenem and panipenem

Among the many different structurally distinct classes of beta-lactams, the carbapenem class is regarded as that which is most potent and which has the widest spectrum of antimicrobial activity. Rapidly bactericidal, and demonstrating time-dependent killing, carbapenemes have a spectrum of antimicrobial activity that includes Gram-positive and Gram-negative aerobic and anaerobic pathogens. Their in-vitro activity includes extended-spectrum beta-lactamase (ESBL)-producing pathogens and carbapenems are currently considered to be the treatment of choice for serious infections due to ESBL-producing organisms. However, isolates acquiring resistance under treatment have been reported. Imipenem, meropenem and ertapenem are licensed in the European Community and panipenem and biapenem are also available in Japan and South Korea. Other carbapenemes are under development.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Carbapenems; Ertapenem; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Humans; Imipenem; Infusions, Parenteral; Meropenem; Thienamycins

The aim of this study was to evaluate the usefulness of carbapenems as initial treatment for febrile neutropenia (FN), and in patients unresponsive to this initial therapy, to evaluate the efficacy of subsequent treatment with aminoglycosides (AGs) or ciprofloxacin (CPFX). FN patients were randomized to receive cefepime (CFPM, control), panipenem/betamiprom (PAPM/BP), or meropenem (MEPM). Defervescence, an outcome endpoint, was evaluated 3 days later. Patients with minimal response were given CPFX or AGs, and their responses were reevaluated on day 7. A total of 255 patients were included. The efficacies of CFPM, PAPM/BP, and MEPM were comparable. In patients unresponsive to this initial therapy, the efficacy of subsequent CPFX and AGs treatments was also similar. There was no significant between-arm difference in cumulative efficacy on days 14 and 30. Adverse reactions were infrequent and mild. In conclusion, PAPM/BP and MEPM are as useful as CFPM as initial therapy for FN, and AGs are as efficacious as CPFX in patients unresponsive to the initial therapy.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Carbapenems; Cefepime; Cephalosporins; Female; Fever; Hematologic Diseases; Humans; Male; Meropenem; Neutropenia; Prospective Studies; Thienamycins; Treatment Outcome; Young Adult

Topics: Acinetobacter baumannii; Acinetobacter Infections; beta-Lactams; Cefoperazone; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Sulbactam; Thienamycins

The antianaerobic activity of tomopenem, a new longer-half-life parenteral carbapenem, was compared with other carbapenems. Tomopenem showed broad activity against 63 reference species. The activity of tomopenem against 293 clinical isolates was potent (MIC(90), 0.06 to 4 microg/ml) and comparable to those of meropenem and doripenem and more potent than that of panipenem.

Topics: Anti-Bacterial Agents; Bacteria, Anaerobic; Carbapenems; Doripenem; Meropenem; Microbial Sensitivity Tests; Thienamycins

Although several high-performance liquid chromatography (HPLC) methods for the determination of serum concentrations of carbapenems have been reported, they are complicated and involve column switching. We established a simple and rapid HPLC method for the determination of serum concentrations of carbapenems, and this method is suitable for routine use in the clinical field. With our HPLC method, the serum concentrations of five commercially available carbapenems could be determined by changing only the methanol/phosphate-buffer ratio in the mobile phase. Serum levels of imipenem, panipenem, and meropenem in mice could be monitored when these carbapenems (20 mg/kg) were administered subcutaneously with cilastatin (20 mg/kg). These results suggest that our simple and rapid HPLC method for the determination of the serum concentrations of carbapenems is useful for pharmacokinetic/pharmacodynamic (PK/PD)-based determination of carbapenem dosage regimens.

Topics: Animals; Anti-Bacterial Agents; Carbapenems; Chromatography, High Pressure Liquid; Imipenem; Male; Meropenem; Mice; Thienamycins

Valproic acid (VPA) is a commonly prescribed anticonvulsant drug for the treatment of various forms of epilepsy. Concomitant administration of VPA and carbapenem antibiotics such as panipenem/ betamipron and meropenem has been reported to decrease the serum level of VPA. We observed seven cases which showed a decrease in serum levels of VPA due to concomitant use of VPA and carbapenem from January 2002 to October 2006 in a 750-bed university hospital, the average decrease of 70.4% was observed. Carbapenem antibiotics administrated concomitantly with VPA were panipenem (1 case), meropenem (3 cases), and imipenem (2 cases), and in one other case imipenem and meropenem were used sequentially. We found the VPA serum levels were significantly decreased with meropenem (n=4) more than with other carbapenem antibiotics (n=4, 89.3% vs. 51.5% decrease, P=0.03). Clinicians should be aware of this potential interaction, pay attention to the failure of seizure control due to decreased serum VPA levels with concomitant use of carbapenem antibiotics, and monitor VPA serum levels for those cases.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anticonvulsants; Carbapenems; Drug Interactions; Drug Therapy, Combination; Epilepsy; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Thienamycins; Valproic Acid

beta-Lactam antibiotics have been suggested to have some degree of convulsive activity and neurotoxicity in experimental animals as well as in clinical situations. We examined the convulsive activities of a new carbapenem antibiotic, (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(3S,5S)-5-[(sulfamoylamino)methyl]-3-pyrrolidinyl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxic acid monohydrate (doripenem) using several animals and compared them with beta-lactam antibiotics. In intravenous (IV) injection studies, imipenem/cilastatin, at 400/400mg/kg produced seizure discharges on electroencephalogram (EEG) accompanied with clonic convulsions in rats. Meropenem showed only wet dog shaking behavior at 200 and 400mg/kg. Doripenem caused no changes in the EEG and behavior in rats at 400mg/kg. Imipenem/cilastatin IV potentiated the pentylenetetrazol (PTZ)-induced convulsions in mice at 250/250 mg/kg, while meropenem, panipenem/betamipron, cefazolin or doripenem did not cause any marked effects at up to 500 mg/kg. In mouse intracerebroventricular (ICV) injection studies, imipenem, panipenem and cefazolin induced clonic convulsions in a dose-dependent manner in mice. Doripenem and meropenem did not induce convulsions at up to 100 microg/mouse. In dog ICV injection studies, imipenem produced generalized seizure discharge with clonic convulsions at 100 microg/dog. Meropenem also produced spikes or seizure discharges at 100, 300 and 1,000 microg/dog. However, doripenem had no effects on the EEG and behavior in dogs at any doses. In in vitro binding studies, imipenem, panipenem, cefazolin and meropenem inhibited [(3)H]muscimol binding to the GABA(A) receptor in mouse brain homogenates while doripenem did not cause any inhibition at up to 10mM. In addition, doripenem had no influence on the anti-convulsant actions of valproic acid in the PTZ- or bicuculine-induced convulsive model. These results clearly indicate that doripenem has no convulsive activity, suggesting that its neurotoxicity may be negligible in clinical use.

Topics: Alanine; Animals; Anti-Bacterial Agents; Anticonvulsants; Carbapenems; Convulsants; Dogs; Doripenem; Drug Interactions; Electroencephalography; Injections, Intravenous; Injections, Intraventricular; Male; Meropenem; Mice; Mice, Inbred ICR; Pentylenetetrazole; Rats; Rats, Wistar; Seizures; Thienamycins; Valproic Acid

Fifty isolates of Streptococcus pneumoniae and 42 isolates of Haemophilus influenzae were isolated from the blood of children admitted to pediatric wards of hospitals in subprefucture between January 1998 and December 2005. The susceptibilities were measured by a microbroth dilution method using a standard broth and a broth containing 4.5% albumin. Against S. pneumoniae, penicillin G, ampicillin, cefotaxime, ceftriaxone, panipenem, meropenem, vancomycin, cefditoren, cefcapene, cefteram, faropenem and tebipenem were used and against H. influenzae, ampicillin, piperacillin, cefotaxime, ceftriaxone, panipenem, meropenem, clavulanic acid/ amoxicillin, cefditoren, cefcapene, cefteram, faropenem and tebipenem were used. Against S. pneumoniae, tebipenem was the highest antimicrobial activity in oral antibiotics (MIC90; < or = 0.06 microg/ml) and panipenem showed the highest activity for intravenous antibiotics (MIC90; < or = 0.12 microg/ml). Against H. influenzae, cefditoren was the highest activity for oral antibiotics (MIC90; < or = 0.06 microg/ml) and meropenem showed the highest activity for intravenous antibiotics (MIC90; < or = 50.06 microg/ml). The MIC90s measured by albumin containing broth were higher than those measured by standard broth. Protein binding rates of ceftriaxone, cefditoren, and faropenem were greater than 90%, and the MIC90 of these antibiotics measured by albumin addition methods were over 4-fold higher than those measured by standard methods.

Topics: Administration, Oral; Anti-Bacterial Agents; Carbapenems; Cephalosporins; Child; Haemophilus influenzae; Humans; Injections, Intravenous; Meropenem; Microbial Sensitivity Tests; Protein Binding; Streptococcus pneumoniae; Thienamycins

Between April 2001 and March 2003, we studied minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of 7 strains of Streptococcus pneumoniae and 8 strains of Haemophilus influenzae isolated from children with meningitis. The age range of the patients was from 4 months to 5 years. Susceptibilities of ampicillin (ABPC), cefotaxime (CTX), panipenem (PAPM), and vancomycin (VCM) in S. pneumoniae and those of ABPC, CTX, ceftriaxone (CTRX), and meropenem (MEPM) in H. influenzae were measured. MICs of ABPC, CTX, PAPM, and VCM to S. pneumoniae were < or = 0.06-2, < or = 0.06-0.5, < or = 0.06, and 0.25-0.5 microgram/ml and MICs of ABPC, CTX, CTRX, and MEPM to H. influenzae were 0.12-64, < or = 0.06-0.5, < or = 0.06-0.12, and < or = 0.06-0.25 microgram/ml, respectively. In 5 of all strains, difference between MIC and MBC to ABPC was observed. Four strains out of them had mutations of penicillin binding protein genes measured by PCR methods.

Topics: Ampicillin; Cefotaxime; Ceftriaxone; Child, Preschool; Drug Resistance, Bacterial; Haemophilus influenzae; Humans; Infant; Meningitis; Meropenem; Streptococcus pneumoniae; Thienamycins; Vancomycin

We evaluated effects of medium composition, including basic amino acid content and pH, on susceptibility to carbapenems such as imipenem, panipenem and meropenem, in clinical isolates of Pseudomonas aeruginosa. Susceptibility to carbapenems was reduced by basic amino acids in the medium, while susceptibilities to ceftazidime and aztreonam were not. Among carbapenems, susceptibility to panipenem was most sharply reduced by addition of basic amino acids to 1:16 Mueller-Hinton agar (MHA). In 174 of 175 clinical isolates, MICs for carbapenems were affected to different degrees by medium composition. One isolate, in which MICs for carbapenems did not differ between MHA and 1:16 MHA, showed reduced production of porin (OprD). Our results suggest that susceptibility to individual carbapenems, especially panipenem, is difficult to evaluate based on MICs for other carbapenems determined on MHA. For a better prediction of antibiotic efficacy, it may be important to evaluate the susceptibility for each carbapenem individually.

Topics: Amino Acids, Basic; Anti-Bacterial Agents; Aztreonam; Carbapenems; Ceftazidime; Culture Media; Humans; Hydrogen-Ion Concentration; Imipenem; Meropenem; Microbial Sensitivity Tests; Porins; Pseudomonas aeruginosa; Thienamycins

To screen effective useful drugs for disease due to M. abscessus, we determined MIC of 3 cephems [ceftazidime (CAZ), cefoxitin (CFX), flomoxef (FMOX)] and 3 carbapenems [imipenem (IPM), panipenem (PAPM), meropenem (MEPM)] for 8 strains of clinically isolated M. abscessus by micro-dilution method using MGIT system. In all the 8 strains, MICs of CAZ are higher than 32 micrograms/ml. MIC50, MIC90, MIC range of CFX are 32 micrograms/ml, > 32 micrograms/ml and 16- > 32 micrograms/ml respectively, and for FMOX, 16 micrograms/ml, 32 micrograms/ml and 16-32 micrograms/ml; for IPM, 8 micrograms/ml, 16 micrograms/ml and 8-16 micrograms/ml; for PAPM, 4 micrograms/ml, 16 micrograms/ml and 4-16 micrograms/ml; for MEPM, 8 micrograms/ml, 16 micrograms/ml and 8-16 micrograms/ml. From this study, it is concluded that FMOX, IPM, PAPM and MEPM can be clinically useful drugs in the treatment of the disease due to M. abscessus.

Topics: Carbapenems; Cefoxitin; Ceftazidime; Cephalosporins; Drug Resistance, Bacterial; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Thienamycins; Tuberculosis, Pulmonary

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

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

The bactericidal activity of biapenem, a new carbapenem, against various efflux-mutants of Pseudomonas aeruginosa was compared with those of imipenem, panipenem, meropenem and ceftazidime. The bactericidal activity of biapenem against P. aeruginosa KG5001, a strain deficient in MexAB-OprM, MexCD-OprJ and MexXY-OprM, was very strong compared with those of imipenem and meropenem. In terms of bactericidal activities, biapenem and imipenem had similar activities against P. aeruginosa KG5003, a strain overexpressing MexAB-OprM, as against P. aeruginosa KG5001, however meropenem and ceftazidime had weaker activities against KG5003 than KG5001. The bactericidal activity against P. aeruginosa KG5007, a strain overexpressing MexCD-OprJ, was observed only by biapenem. The bactericidal activity of biapenem was strong and not influenced by all of these three efflux systems.

Topics: Anti-Bacterial Agents; Ceftazidime; Cephalosporins; Drug Resistance, Bacterial; Imipenem; Meropenem; Mutation; Pseudomonas aeruginosa; Thienamycins

The carbapenem susceptibility of 32 strains of Pseudomonas aeruginosa recently isolated in Kakogawa municipal hospital was investigated. The MIC ranges of imipenem, panipenem, and meropenem were 0.25-16 mg/L, 0.5-16 mg/L, and < 0.03-4 mg/L, respectively, and meropenem showed the highest antipseudomonal activity among the three carbapenems tested. In the analysis based on the MIC interpretive standards established by NCCLS, the resistance rates of test strains for imipenem, panipenem, and meropenem were 6.3%, 15.6%, and 0%, respectively. We also investigated the in vitro combined effect of imipenem or meropenem with amikacin against another 20 isolates of P. aeruginosa by checkerboard titration assay. Antagonism (minimum FIC index > 2) was not observed in any combinations against all strains tested. Super-additive effects (minimum FIC index < 1) in the combination of imipenem and amikacin were observed in eight (40%) strains tested. In contrast, in the combination of meropenem and amikacin, super-additive effects were observed in 14 isolates (70%). These results suggested that meropenem is superior to imipenem in combined effect with amikacin against P. aeruginosa. In conclusion, meropenem showed higher antipseudomonal activities than other carbapenems tested in both conditions, alone and in combination with amikacin. With regard to the clinical efficacy and prevention of antibiotic resistance, meropenem monotherapy or combination therapy with aminoglycoside is the most superior treatment for pseudomonal infections, and the findings in this study suggest that meropenem is still clinically very useful.

Topics: Amikacin; Anti-Bacterial Agents; Carbapenems; Drug Synergism; Drug Therapy, Combination; Imipenem; Meropenem; Pseudomonas aeruginosa; Thienamycins

The rapid bactericidal activities of panipenem (PAPM), imipenem (IPM), and meropenem (MEPM) against Pseudomonas aeruginosa were investigated by using in vitro pharmacodynamic model simulating the human plasma concentrations after intravenous drip infusion at 500 mg for 0.5 hours. Against P. aeruginosa PAO1, PAPM and IPM showed rapider reduction in viable cell counts than MEPM at 0.5 hours after exposure. All drugs showed more than 3 log10 reduction in viable cell counts at 2 hours after exposure and bacterial regrowth was not observed throughout 6 hours. The initial bactericidal activities of the drugs against 4 clinical isolates within 1 hour after exposure were also investigated by the same method. Against P. aeruginosa strain 12,475, the 3 drugs showed similar initial bactericidal activity but PAPM and IPM showed stronger initial bactericidal activity than MEPM against the other strains as did against P. aeruginosa PAO1. The morphological change of a strain 12,489, for which the initial bactericidal activities were different largely, after 0.5 hours exposure to simulated drug-concentrations was investigated by scanning electron microscope. PAPM and IPM induced morphological changes in most of the cells and cell lysis and bulge formation. On the other hand, MEPM induced changes of the surface structure of cells and slightly elongated cells, but not cell lysis.

Topics: Carbapenems; Drug Resistance, Bacterial; Humans; Imipenem; Meropenem; Microscopy, Electron, Scanning; Models, Biological; Pseudomonas aeruginosa; Thienamycins

We determined the antibacterial activities of 4 carbapenems (imipenem, panipenem, meropenem and biapenem) and 2 forth generation cephems (cefozopran and cefepime) against 850 bacterial strains (18 species) isolated during the period from January 1998 through September 2000. The 4 carbapenems showed excellent antibacterial activities against methicillin-susceptible S. aureus (MSSA), S. pneumoniae, E. faecalis, P. aeruginosa, M. (B). catarrhalis, B. fragilis and Peptostreptococcus spp. as compared with the cephems except the activity of panipenem against P. aeruginosa. Meropenem showed the highest antibacterial activity against 10 species of all Gram-negative strains determined. The antibacterial activities of 2 forth generation cephems against 6 species of Enterobacteriaceae were equal to or higher than those of carbapenems except meropenem. All drugs showed low antibacterial activities against methicillin-resistant S. aureus (MRSA).

Topics: Bacteria; Carbapenems; Cefepime; Cefozopran; Cephalosporins; Imipenem; Meropenem; Thienamycins

Comparative antibacterial activity of imipenem (IPM), panipenem (PAPM), meropenem (MEPM) and biapenem (BIPM) was determined against 288 clinical isolates of P. aeruginosa collected from various hospitals in 2000. The order of activity by comparison of MIC50/MIC80/MIC90 was: MEPM (1/4/8 micrograms/ml) > BIPM (1/4/16 micrograms/ml) > IPM (2/4/16 micrograms/ml) > PAPM (8/16/32 micrograms/ml). Moreover, the order of activity against 75 strains of P. aeruginosa (MIC of CAZ, AZT was > or = 16 micrograms/ml and MIC of IPM, MEPM was < or = 8 micrograms/ml) by comparison of MIC50/MIC80/MIC90 was: BIPM (1/2/8 micrograms/ml) > or = MEPM (1/4/8 micrograms/ml) > or = IPM (2/2/8 micrograms/ml) > PAPM (8/16/16 micrograms/ml). Judging from both correlation between the MICs of carbapenems and relationship between class C beta-lactamase activity and drug susceptibility of carbapenems, it becomes apparent that carbapenems, especially BIPM and MEPM will be useful for treatment of antipseudomonal cephem resistant pseudomonas infection.

Topics: beta-Lactamases; Carbapenems; Drug Resistance, Microbial; Imipenem; Meropenem; Pseudomonas aeruginosa; Thienamycins

During October and December of each year of from 1994 to 1996, 3,849 strains of 10 species of bacteria were isolated from clinical materials in 21 institutions nationwide. The minimum inhibitory concentrations (MICs) for these bacteria of four carbapenems (imipenem [IPM], panipenem [PAPM], meropenem [MEPM], and biapenem [BIPM]) and other representative antibacterial agents were measured to investigate annual changes in antibacterial activity. Carbapenems showed potent activity against methicillin-sensitive S. aureus (MSSA), S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, S. marcescens, and the B. fragilis group, with the activity being stable. However, these drugs showed weak activity against methicillin-resistant S. aureus (MRSA) and P. aeruginosa. The antibacterial activity (MIC90) against the tested organisms generally remained stable. Particularly, there was annual improvement of the MIC90 values of IPM and BIPM for S. pneumoniae, as well as the values of IPM and PAPM for H. influenzae, and those of IPM, PAPM, and BIPM for S. marcescens. On the other hand, the activity of carbapenems (including IPM) against MRSA was not necessarily strong, but there was annual improvement of MIC90 values.

Topics: Bacteria; Carbapenems; Drug Resistance, Microbial; Humans; Imipenem; Japan; Meropenem; Multicenter Studies as Topic; Thienamycins; Time Factors

The frequency and the antibacterial sensitivity of Streptococcus pneumoniae strains isolated from 6 key hospitals (in 5 areas) and 1 otorhinolaryngology clinic in Gifu Prefecture from February to March, 1999, were investigated with several antibiotics. A total of 128 strains of Streptococcus pneumoniae were isolated throughout the study: 47 strains (36.7%) of penicillin-susceptible S. pneumoniae (PSSP), 51 strains (39.8%) of penicillin-intermediate S. pneumoniae (PISP), and 30 strains (23.4%) of penicillin-resistant S. pneumoniae (PRSP); the resistant bacteria being relatively prominent. In these hospitals, PSSP was isolated by 38.8% in all the key hospitals and by 30% in the otolaryngology clinic with almost no discernible difference. PISP was isolated by 63.3%, higher in the otolaryngology clinic and PRSP by 28.6%, higher in the key hospitals conversely. The MIC90s in PISP and PRSP were determined with the antibiotics. In result, only cefditoren (CDTR) showed favorable antibacterial activities with the MIC90 of 0.78 microgram/ml among penicillins or oral cephems. The MIC90s of carbapenems such as imipenem (IPM), meropenem (MEPM), and panipenem (PAPM) were less than 0.39 microgram/ml; particularly, PAPM showed the highest antibacterial activities. Among new quinolones such as tosufloxacin (TFLX), levofloxacin (LVFX), sparfloxacin (SPFX), and ciprofloxacin (CPFX), TFLX showed the highest antibacterial activities with the MIC90 of 0.39 microgram/ml. Other agents showed very low antibacterial activities as the MIC90s were 25 micrograms/ml in minocycline (MINO) and more than 100 micrograms/ml in clarithromycin (CAM) and clindamycin (CLDM).

Topics: Amoxicillin; Anti-Bacterial Agents; Cefaclor; Cefdinir; Cefixime; Cefmenoxime; Cefpodoxime; Ceftizoxime; Cephalosporins; Ciprofloxacin; Clarithromycin; Clindamycin; Drug Resistance, Microbial; Fluoroquinolones; Humans; Imipenem; Japan; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Minocycline; Naphthyridines; Ofloxacin; Penicillin G; Penicillins; Streptococcus pneumoniae; Thienamycins

Minimum inhibitory concentration (MIC) has been generally used to evaluate the activity of antimicrobial agents. However, there is some discrepancy between clinical efficacy and the MIC value. We studied the relationship between initial bactericidal activity of imipenem (IPM), panipenem (PAPM), meropenem (MEPM), ceftazidime (CAZ) and amikacin (AMK) and the respective MIC values against Pseudomonas aeruginosa PAO1. Initial bactericidal activity was defined as percent reduction of initial bacterial cell concentration (10(6) cells/ml) after 1 hour incubation following addition of antibiotic. The concentration of antibiotic used in this experiment was the blood level of each antibiotic at 3 hours after administration by drip infusion of the usual dose (IPM, PAPM and CAZ were 1 g for 1 hour drip infusion, MEPM was 1 g for 0.5 hours drip infusion and AMK was 200 mg for 1 hour drip infusion, respectively). The antibiotic concentration of IPM, PAPM, MEPM, CAZ and AMK were 8.77 micrograms/ml, 6.37 micrograms/ml, 4.12 micrograms/ml, 12.0 micrograms/ml and 5.18 micrograms/ml, respectively. MICs of IPM, PAPM, MEPM, CAZ and AMK were 2 micrograms/ml, 64 micrograms/ml, 1 microgram/ml, 1 microgram/ml and 2 micrograms/ml, respectively. Initial bactericidal activity of IPM, PAPM, MEPM, and CAZ against P. aeruginosa PAO1 was 98.2%, 86.1%, 48.1%, and 43.4% reduction in bacterial concentration, respectively. AMK shows the strongest initial bactericidal activity with more than 99.9%. The killing speed of IPM was obviously the most rapid among the three carbapenems. The MIC of PAPM was significantly higher than the other antibiotics, and the initial bactericidal activity of PAPM was second to IPM. We can classify antibiotics into two groups based on initial bactericidal activity against P. aeruginosa; one class is antibiotics having rapid initial killing such as AMK, IPM and PAPM, the other is CAZ, MEPM showing slow initial killing.

Topics: Amikacin; Anti-Bacterial Agents; Ceftazidime; Cephalosporins; Imipenem; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Thienamycins

The relationship between morphological changes and endotoxin release induced in vitro by carbapenems in a clinical isolate of Pseudomonas aeruginosa was examined. The time-course and magnitude of endotoxin release induced varied among imipenem, panipenem, meropenem and biapenem and related to the morphological changes caused by these agents which variously affected cell shape, cell-wall disintegration and cell lysis. The amount of endotoxin released by carbapenem-treated cells correlated with both the cell-wall morphology and bacterial shape immediately before lysis. Meropenem and biapenem caused markedly increased endotoxin release during cell lysis and cell-wall disintegration, whereas imipenem and panipenem caused much less release of endotoxin.

Topics: Carbapenems; Endotoxins; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins

Research groups were formed in 21 institutions nationwide to investigate carbapenem resistance. The activities of various antibacterial agents, principally carbapenems, were tested against clinical isolates collected from these institutions. The broth microdilution method was used to determine the minimum inhibitory concentrations (MIC) of 17 antibacterial agents for 1,241 strains of 11 bacterial species isolated at all institutions between October and December 1996. The results were as follows: Carbapenems exhibited strong antibacterial activities against MSSA and Streptococcus pneumoniae and showed low activities against MRSA. Their activities against Enterococcus faecalis were comparable to that of ampicillin and piperacillin. The carbapenems showed high activities against Haemophilis influenzae, Escherichia coli, Klebsiella pneumoniae. Enterobacter cloacae. Serratia marcescens and Bacteroides fragilis group. Their activities were greater than that exhibited by other beta-lactam antibacterial agents, but some resistant strains of Serratia marcescens were detected. The antibacterial activity of carbapenems against Pseudomonas aeruginosa was comparable to that of CAZ, and there were some resistant strains.

Topics: Carbapenems; Drug Resistance, Microbial; Gram-Negative Bacteria; Gram-Positive Cocci; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Thienamycins; Time Factors

The susceptibility of 260 strains of Pseudomonas aeruginosa to several antibiotics and the mechanism of resistance to carbapenems were investigated. The number of strains of P. aeruginosa moderately resistant or resistant to ofloxacin, ceftazidime and imipenem (IPM) were 76 (29.2%), 31 (11.9%) and 30 (11.5%), respectively. There was no clear relationship between the drug resistance of P. aeruginosa and serum type. Fourteen strains (46.6%) out of 30 IPM-resistant strains were susceptible to meropenem (MEPM). Twenty seven (90.0%) IPM-resistant strains showed cross resistant to panipenem (PAPM), and 12 strains (44.4%) out of the 27 strains showed high susceptibility to MEPM. P. aeruginosa becomes resistant to IPM and PAPM only by the decrease in the outer membrane permeability of these carbapenems. In contrast, P. aeruginosa becomes equally resistant to MEPM by concurrent occurrence of the increase in the efflux of the antibiotics and the decrease in the outer membrane permeability of the antibiotics. The possibility that both mechanisms are taken place concurrently in P. aeruginosa is considered to be low, and it was also supported by the results of the present study.

Topics: Anti-Infective Agents; beta-Lactam Resistance; Carbapenems; Ceftazidime; Cephalosporins; Imipenem; Meropenem; Ofloxacin; Pseudomonas aeruginosa; Thienamycins

Eleven clinical strains of MRSA which were detected as heterogeneously-resistant to vancomycin (hetero-VRSA) on Mu3-medium (a newly devised hetero-VRSA detecting medium) were subjected to a study to explore the therapeutic possibility of combination therapy. Combination effects of teicoplanin with six different beta-lactam antibiotics (imipenem, panipenem, meropenem, flomoxef, sulbactam/ampicillin, cefoselis), arbekacin, and minocycline were evaluated on the strains of Mu3, Mu50 and the above 11 strains. Combination of teicoplanin with five beta-lactam antibiotics individually (except for cefoselis) showed a synergistic effect, while that with cefoselis showed synergistic or additive effect. Neither indifference nor antagonism effect was observed in combination of seicoplanin with beta-lactam antibiotics on these MRSA strains. The degree of synergistic effect in combination with teicoplanin was the strongest in imipenem, followed by panipenem > meropenem > flomoxef > sulbactam/ampicillin > cefoselis in this order. The average FIC index of the beta-lactam antibiotics against these strains was 0.113, 0.124, 0.163, 0.230, 0.264 and 0.388, respectively. Arbekacin and minocycline showed variable of effects in combination with teicoplanine. In the case of arbekacin, the ratio of synergy, addition, indifference, and antagonism were 30.8, 30.8, 0 and 38.4%, respectively, and in the case of minocycline, they were 15.4. 7.7, 0 and 76.9%, respectively. Vancomycin activity against hetero-VRSA and VRSA is antagonized with beta-lactam antibiotics, while teicoplanin activity is synergistic or additive. It is known that MRSA is relatively easy to emerge resistance to teicoplanin. Therefore, teicoplanin is not desirable for a monotherapy. However, in a combination with beta-lactam antibiotics, teicoplanin appeared to be a promising agent for the treatment of MRSA infection.

Topics: Anti-Bacterial Agents; Drug Synergism; Drug Therapy, Combination; Imipenem; Meropenem; Methicillin Resistance; Staphylococcus aureus; Teicoplanin; Thienamycins; Vancomycin Resistance

Antibacterial activities of four carbapenems, imipenem, panipenem, meropenem, and biapenem, were determined using 353 strains belonging to 18 bacterial species which were isolated from clinical materials at Ehime University Hospital. The MIC values of these carbapenems against MRSA were widely distributed between 0.1 and 100 micrograms/ml, and MIC90 values of these 4 carbapenems were 25-50 micrograms/ml. Any of these carbapenems prevented the bacterial growth of enterobacteriaceae of 8 bacterial species excluding S. macrescens at concentrations of 1 microgram/ml or less. The MIC values against P. aeruginosa showed relatively wide distribution, being 0.39-25 micrograms/ml for imipenem, 0.2-25 micrograms/ml for panipenem, 0.1-12.5 micrograms/ml for meropenem, and 0.2-12.5 micrograms/ml for biapenem. From those results, it was confirmed that any of the carbapenems tested had a wide antibacterial spectrum and strong antibacterial activities.

Topics: Bacteria; Enterobacteriaceae; Imipenem; Meropenem; Methicillin Resistance; Pseudomonas aeruginosa; Staphylococcus aureus; Thienamycins

The in vitro antibacterial activity of biapenem (BIPM), a new carbapenem antibiotic, was compared with those of imipenem (IPM), panipenem (PAPM), meropenem (MEPM), ceftazidime (CAZ) and piperacillin (PIPC) against 280 isolates of 9 respiratory pathogens. The MIC90s of biapenem (BIPM) for methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa, and Haemophilus influenzae were 0.12, 32, 0.25, 0.06, 4 and 8 micrograms/ml, respectively. In comparison with other antibiotics, the activity of biapenem (BIPM) for P. aeruginosa was as potent as meropenem (MEPM), but for H. influenzae it was slightly less than those of other antibiotics, and for other respiratory pathogens it was as potent as those of other antibiotics. The MIC90s of biapenem (BIPM) for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Serratia marcescens were 0.06, 1, 1, 0.5 microgram/ml, respectively, and which were equal to or somewhat lower than those of other antibiotics. Biapenem (BIPM) showed strong activity against Gram-positive and Gram-negative pathogens, especially P. aeruginosa in general. Based on these results, biapenem (BIPM) is seemed to be highly useful antibiotic for the treatment of respiratory infections with several organism.

Topics: Bacteria; Carbapenems; Ceftazidime; Cephalosporins; Drug Resistance, Microbial; Humans; Imipenem; Meropenem; Penicillins; Piperacillin; Respiratory Tract Infections; Thienamycins; Time Factors

In order to evaluate antimicrobial activity of meropenem (MEPM), minimum inhibitory concentrations (MICs) of MEPM and control drugs were determined against clinical isolates in 1997. The results were as follows; 1. Antimicrobial activities of MEPM against Gram-positive bacteria were stronger than those of cephems (CEPs) and were approximately equal to those of imipenem (IPM) and panipenem (PAPM). 2. Carbapenems showed strong antimicrobial activities against Enterobacteriaceae, Glucose non-fermentative Gram-negative rods and Bacteroides fragilis group that were multiple drug resistant including the third generation CEPs. Antimicrobial activities of MEPM against these organisms were stronger than those of IPM and PAPM. By comparing antimicrobial activities of MEPM against Gram-negative bacteria in 1997 with those obtained in 1993, increase of resistance was not observed. 3. MIC-ranges of MEPM were low against the resistant strains of Pseudomonas aeruginosa to IPM and PAPM. It was considered that these resistant strains were not expressing oprD products (D2 porin protein), forming main outer membrane porin channels of carbapenems and basic amino acids.

Topics: Bacteria; Carbapenems; Cephalosporins; Drug Resistance, Microbial; Humans; Imipenem; Meropenem; Thienamycins; Time Factors

Antimicrobial activities of meropenem (MEPM), imipenem (IPM), panipenem (PAPM), ceftazidime (CAZ), cefozopran (CZOP), aztreonam (AZT), norfloxacin (NFLX) and tetracycline (TC) against clinically isolated Gram-negative bacilli [271 strains of Enterobacteriaceae and 242 strains non-fermentative Gram-negative bacteria (NFB)] were investigated. Among carbapenem antibiotics, MEPM showed the lowest MIC90, which activity was about four-hold higher than those of IPM and PAPM. The activity of IPM was equal or slightly superior to that of PAPM. Resistance to IPM (> 16 micrograms/ml) was observed in 3 strains of Enterobacteriaceae (1.1%) and 14 strains of NFB (5.8%). It is conceivable that these strains produce metallo-beta-lactamase. Referring to the correlation among MICs of MEPM, IPM and PAPM, 3 strains in 3 species of Enterobacteriaceae showed cross resistance to carbapenems; while 14 strains of NFB showed cross resistance to MEPM and IPM, 15 strains to MEPM and PAPM, and 29 strains to IPM and PAPM, and all of these strains were Pseudomonas aeruginosa. Fifteen of 29 strains of IPM-resistant and 77 of 92 strains of PAPM-resistant P. aeruginosa were susceptible to MEPM. Thirty-three strains (12%) of the Enterobacteriaceae were resistant to CAZ and AZT (> or = 32 micrograms/ml) and these were considered as ESBL-producing strains.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Aztreonam; Carbapenems; Cefozopran; Ceftazidime; Cephalosporins; Drug Resistance, Microbial; Enterobacteriaceae; Gram-Negative Bacteria; Humans; Imipenem; Meropenem; Monobactams; Norfloxacin; Tetracycline; Thienamycins

The anti-H. influenzae activity of meropenem (1a) was much higher than those of imipenem (4). panipenem (2b) and biapenem (7). To clarify the major structural features responsible for the anti-H. influenzae activity of carbapenem compounds, the structure-activity relationship to the anti-H. influenzae activity was investigated. The anti-H. influenzae activities of meropenem (1a) and 1 beta-methyl-panipenem (2a) were much higher than those of desmethyl-meropenem (1b) and panipenem (2b). respectively. Two carbapenems (5, 6) and imipenem (4), that have a strong basic C-2 side chain, showed lower anti-H. influenzae activity than meropenem (1a) having a weakly basic C-2 side chain and N-acetyl thienamycin (3) having a neutral C-2 side chain, respectively. As a result, we found that the introduction of the 1 beta-methyl group or the reduction of the basicity (cationic character) of the C-2 side chain increased the antimicrobial activity and bactericidal activity of carbapenems against H. influenzae due to their increased affinity for PBP-4 and PBP-5.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Carrier Proteins; Haemophilus influenzae; Hexosyltransferases; Imipenem; Meropenem; Methylation; Muramoylpentapeptide Carboxypeptidase; Penicillin-Binding Proteins; Penicillins; Peptidyl Transferases; Protein Binding; Structure-Activity Relationship; Thienamycins

Research groups were formed in 20 institutions nationwide to investigate carbapenem resistance of clinical isolates. Activities of various antibacterial agents, principally carbapenems, were tested against clinical isolates collected from these institutions. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of 17 antibacterial agents for 1,326 strains of 11 bacterial species isolated at the institutions between October and December 1994. The results are as follows: 1. Carbapenems exhibited strong antibacterial activities against MSSA and Streptococcus pneumoniae. Their activities against Enterococcus faecalis were comparable to that of ABPC. Carbapenems showed low activities against MRSA. 2. OFLX exhibited the greatest antibacterial activity against Haemophilus influenzae, followed by MEPM. Antibacterial activities of the other carbapenems were comparable to those of FMOX, CTM, and ABPC. 3. The carbapenems showed high activities against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Bacteroides fragilis group. Their activities were greater than those exhibited by other beta-lactam antibacterial agents. The carbapenems also exhibited stronger antibacterial activities against Serratia marcescens than the other beta-lactam antibacterial agents, but some resistant strains were detected. 4. The antibacterial activities of carbapenems against Pseudomonas aeruginosa were comparable to those of CAZ, AZT, AMK.

Topics: 4-Quinolones; Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Carbapenems; Cephalosporins; Drug Resistance, Microbial; Gram-Negative Bacteria; Gram-Positive Cocci; Haemophilus influenzae; Humans; Imipenem; Meropenem; Monobactams; Penicillins; Pseudomonas aeruginosa; Serratia marcescens; Thienamycins

We determined in vitro combined effects of vancomycin (VCM) plus carbapenems (CRBs) on 12 methicillin-resistant Staphylococcus aureus (MRSA) which are resistant to CRBs. Combinations of VCM plus imipenem (IPM) and VCM plus panipenem (PAPM) and VCM plus meropenem (MEPM) indicated synergistic effects, fractional inhibitory concentration (FIC) indices of < or = 0.05, against 67%, 75%, 67% of the strains, respectively. Against forty two percent of strains tested, 1 MIC of VCM was equal to 1 MBC, and similarly, IPM, PAPM and MEPM had 1 MIC = 1 MBC against 42%, 67% and 75% of the strains tested, respectively. Combinations of VCM plus IPM and VCM plus PAPM and VCM plus MEPM showed synergistic effects, hence a fractional bactericidal concentration (FBC) index of < or = 0.50, against 42%, 50%, 75% of the strains, respectively, and the combination of VCM plus MEPM was most synergistic. These results suggest that combination therapy of VCM with CRB is useful for the treatment of MRSA infection in patients with renal dysfunction.

Topics: Anti-Bacterial Agents; Carbapenems; Imipenem; Meropenem; Methicillin Resistance; Staphylococcus aureus; Thienamycins; Vancomycin

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

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

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

The neurotoxicity of meropenem was much lower than that of both imipenem and panipenem after intraventricular administration to mice. To clarify the major structural features responsible for the induction of convulsions by carbapenem antibiotics, the structure-activity relationship on convulsant activity was investigated in N-acetyl-2-pyrroline and cyclopentene derivatives which correspond to the 5-membered ring containing the C-2 side chain of carbapenem antibiotics. Among these derivatives, compounds with strong basicity in the side chain showed convulsant activity similar to that of the parent carbapenem compounds. In addition to the strength of the basicity of the amino group, the distance from the carboxyl to the amino group and steric crowding around the amino group also appeared to play an important role in the induction of convulsions. The results of gamma aminobutyric acid (GABAA) receptor binding assays indicated that the induction of convulsions was caused predominantly by the inhibition of GABAA-mediated inhibitory transmission. However, the in vivo convulsant activity of some of these compounds did not correlate with their in vitro inhibitory effect on GABAA receptor binding.

Topics: Animals; Imipenem; Meropenem; Mice; Mice, Inbred ICR; Receptors, GABA; Seizures; Structure-Activity Relationship; Thienamycins

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Carbapenems; Drug Synergism; Enzyme Inhibitors; Imipenem; Meropenem; Pseudomonas aeruginosa; Sulbactam; Thienamycins

We compared the antimicrobial activities of penems in human urine with those in Mueller-Hinton broth in order to clarify the usefulness of penems for urinary tract infections. Furthermore, we also investigated the influence of urine components, such as pH, magnesium concentration and calcium concentration, on the antimicrobial activities of penems. Three penems, i.e., imipenem, panipenem and meropenem were employed. And two bacterial strains, i.e., Escherichia coli NIHJ JC-2 and Pseudomonas aeruginosa 18s, were tested. There was no significant difference in MBCs between human urine and Mueller-Hinton broth against E. coli. However, MBCs of penems in human urine was lower than those in Mueller-Hinton broth against P. aeruginosa. On the other hand, MBCs of penems against these two strains were low when urine pH was high or urine calcium concentration was low. No influence of urine magnesium concentration on MBCs of penems was seen. From these results, it was suggested that we should measure the antimicrobial activities of penems not only in Mueller-Hinton broth, but also in human urine, when we administer penems to patients with urinary tract infections. And we should foresee the clinical effects of penems against urinary tract infections paying attention to urine pH of the patients.

Topics: Cations, Divalent; Escherichia coli; Humans; Hydrogen-Ion Concentration; Imipenem; Meropenem; Pseudomonas aeruginosa; Thienamycins; Urinary Tract Infections; Urine