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PubMed2004

Detection of metallo beta-lactamase production and antibiotic resistance with E-test method in pseudomonas, acinetobacter and klebsiella strains, in Turkey.

The metallo beta-lactamase (MBL) mediated resistance patterns remain unknown in most countries. We aimed to investigate the existence and antimicrobial resistance of MBL-producing strains among carbapenem-resistant gram-negative bacteria that were isolated from nosocomial infections in patients in an university hospital in Turkey. Fifteen of 52 Pseudomonas aeruginosa strains (29%), 5 of 24 Acinetobacter baumanii strains (21%), and 2 of 2 Klebsiella pneumoniae strains (100%) were found to be metallo enzyme producers, with the Etest MBL technique. The in vitro antibiotic susceptibility of the MBL-positive organisms was investigated by the Etest method. Of the ten drugs tested, isepamicin was the most active agent against the MBL-producing strains. Overall, the rank order of activity of the ten antibiotics, in terms of the percentages of susceptible strains, was: isepamicin, 73%; ciprofloxacin, 64%; amikacin, 59%; aztreonam, 18%; tobramycin, 18%; meropenem, 14%; cefoperazone-sulbactam, 5%; piperacillin-tazobactam, 0%; ticarcillin-clavulanate, 0%; and cefepim, 0%. The meropenem minimum inhibitory concentrations (MICs) of the metallo enzyme-producing and nonproducing carbapenem-resistant strains were compared, and the MBL-producers were found to have higher meropenem MICs than the nonMBL-producing carbapenem-resistant strains. Early preventive measures should be taken against MBL-producing nosocomial pathogens that are associated with wide spread and high antimicrobial resistance.

Acinetobacter baumannii↗

PubMed2005

Study of the synergism between carbapenems and vancomycin or teicoplanin against MRSA, focusing on S-4661, a carbapenem newly developed in Japan.

S-4661 is a methylcarbapenem antibiotic newly developed in Japan. We evaluated the combined actions of carbapenems, including S-4661 and vancomycin or teicoplanin, against 27 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from the blood of patients admitted to Keio University Hospital, using the checkerboard technique. The minimum inhibitory concentrations (MICs) were determined by the Mueller-Hinton agar method. Most of the strains were highly resistant to carbapenems. Synergy with S-4661, panipenem, meropenem or imipenem, and vancomycin was detected against 92% of the strains tested. Synergy with S-4661, panipenem, meropenem or imipenem, and teicoplanin was detected against 74% of the strains tested. The results of our study suggest that combination therapy of vancomycin or teicoplanin with any of S-4661, panipenem, meropenem, or imipenem would be effective for severe infections due to MRSA strains that are resistant to carbapenems.

Anti-Bacterial Agents↗

PubMed1995

Comparison of susceptibility to extended-spectrum beta-lactam antibiotics and ciprofloxacin among gram-negative bacilli isolated from intensive care units.

The in vitro activities of extended-spectrum beta-lactam antibiotics (including piperacillin, cefotaxime, ceftriaxone, ceftazidime, cefepime, imipenem, and meropenems) were assessed and compared with the activity of ciprofloxacin against 366 clinical Gram-negative bacilli isolates from the intensive care units of Taichung Veterans General Hospital. The most prevalent species isolated were Pseudomonas aeruginosa and Acinetobacter baumannii. The activities of ceftazidime, cefepime, imipenem, and meropenem against these isolates were comparable to that of ciprofloxacin. Meropenem was found to be the most potent extended-spectrum beta-lactam antibiotic tested and the MIC50s and MIC90s for most of these multiresistant strains were lower than those of imipenem, ceftazidime, and cefepime, except for Stenotrophomonas maltophilia. The extended-spectrum beta-lactam antibiotics that were still active against S. maltophilia were piperacillin and ceftazidime. More than 50% of Enterobacter spp. were resistant to third-generation cephalosporins and piperacillin, but they remained susceptible to carbapenems and cefepime.

Anti-Bacterial Agents↗

PubMed2003

Synthesis and biological activity of novel 1beta-methylcarbapenems with oxyiminopyrrolidinylamide moiety.

The synthesis and antibacterial activity of novel 1beta-methylcarbapenems 1a-f bearing oxyiminopyrrolidinylamide moiety at C-5 position of pyrrolidine are described. Most compounds exhibited comparable antibacterial activity to meropenem against a wide range of Gram-positive and Gram-negative organisms including Pseudomonas aeruginosa isolates. Of these carbapenems, 1a showed potent and broad spectrum of antibacterial activity and similar stability to DHP-I to meropenem. Against clinical isolates of 40 Gram-negative bacterial species including MDR and ESBL-producing strains, the selected carbapenem 1a possessed excellent in vitro activity except for MDR P. aeruginosa, and was comparable in potency to meropenem.

Anti-Bacterial Agents↗

PubMed2005

Simulation of antibiotic pharmacodynamic exposure for the empiric treatment of nosocomial bloodstream infections: a report from the OPTAMA program.

OBJECTIVE: We developed a model to predict the pharmacodynamic exposure of antibiotics against bacteria commonly implicated in nosocomial bloodstream infections to determine which dosage regimens would provide the greatest likelihood of obtaining a bactericidal effect. METHODS: Pharmacodynamic exposures were simulated for 5000 subjects receiving standard doses of ceftazidime, cefepime, piperacillin/tazobactam, meropenem, imipenem, or ciprofloxacin. Exposures were indexed to the MICs of bacteria weighted by their prevalence in causing nosocomial bloodstream infections, derived from 2002 SENTRY data. Enterococci were excluded. MIC data were derived from the 2003 Meropenem Yearly Surveillance Test Information Collection resistance study. The probabilities of achieving bactericidal exposures (ie, target attainment) for each antibiotic regimen were compared. The effect of increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) on attainment of bactericidal targets was tested. RESULTS: All dosage regimens except ciprofloxacin and ceftazidime 1 g q8h achieved >90% likelihood of bactericidal exposure. The rank order of target attainment was as follows: imipenem 500 mg q6h, 100.0%; imipenem 1 g q8h, 99.9%; cefepime 2 g q12h, 99.4%; meropenem 1 g q8h, 98.4%; cefepime 1 g q12h, 98.2%; piperacillin/tazobactam 3.375 g q6h, 97.9%; piperacillin/tazobactam 4.5 gq8h, 95.0%; ceftazidime 2 g q8h, 94.2%; ceftazidime 1 g q8h, 71.7%; ciprofloxacin 400 mg q8h, 63.3%; and ciprofloxacin 400 mg q12h,63.0%. Target attainments dropped to <90% for all agents when MRSA was modeled at > or =10% prevalence. CONCLUSIONS: The results of this model analysis suggest that standard doses of the carbapenems, piperacillin/tazobactam, and cefepime, and higher doses of ceftazidime, may provide optimal likelihood of achieving bactericidal exposure against pathogens implicated in nosocomial bloodstream infections, excluding MRSA and enterococci. When MRSA rates are > or =10%, therapy with an antibiotic that has activity against this phenotype should be empirically initiated.

Anti-Bacterial Agents↗

PubMed2005

Prevalence and antimicrobial susceptibility data for extended-spectrum beta-lactamase- and AmpC-producing Enterobacteriaceae from the MYSTIC Program in Europe and the United States (1997-2004).

This article presents prevalence and susceptibility data from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program in Europe (1997-2004) and the United States (1999-2004) for Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBL) and/or AmpC beta-lactamases. For ESBL-producing isolates, the prevalence of Escherichia coli and Klebsiella spp. in Europe and Enterobacter spp. in the United States increased over time. For AmpC-producing isolates, the prevalence of Enterobacter spp. and Citrobacter spp. decreased over time in Europe and the United States, respectively. Compared with other antimicrobial agents, meropenem and imipenem had greatest activity against ESBL-producing E. coli and Klebsiella spp. in both Europe (96.9-100.0%) and the United States (100.0%). Such activity was also found for AmpC-producing Enterobacteriaceae in Europe (50.0-100.0%), and Enterobacter spp. and Citrobacter spp. from the United States (100.0% for both). The continued efficacy of carbapenems such as meropenem confirms that these remain first-line agents for treatment of nosocomial infections caused by Enterobacteriaceae-producing ESBL or AmpC beta-lactamases.

Anti-Bacterial Agents↗

PubMed2026

Activity of Aztreonam-avibactam and Ceftazidime-Avibactam against Enterobacterales and Pseudomonas aeruginosa causing infections in patients hospitalized in hematology, oncology, and transplant units from United States medical centres (2019-2024).

Immunosuppression increases the risks and severity of infections and is associated with a higher incidence of infection with multidrug-resistant (MDR) pathogens. We evaluated the antimicrobial susceptibility of Enterobacterales and Pseudomonas aeruginosa from patients hospitalized in hospital units where the frequency of immunosuppressed patients is very high. Bacterial isolates were consecutively collected (1/patient) from 75 US medical centres in 2019-2024 and susceptibility tested by broth microdilution. Enterobacterales (n = 2,407) and P. aeruginosa (n = 485) from patients hospitalized in hematology, oncology, and transplant units were evaluated. Carbapenem-resistant Enterobacterales (CRE) were screened for β-lactamases by whole genome sequencing. Enterobacterales were mainly from bloodstream infection (BSI; 53.6%) and urinary tract infection (19.9%) and P. aeruginosa were mainly from BSI (37.9%) and pneumonia (35.0%). Aztreonam-avibactam, ceftazidime-avibactam, and meropenem-vaborbactam were highly active against Enterobacterales (99.9-99.4% susceptible), including MDR isolates (99.6-98.1% susceptible), but only aztreonam-avibactam exhibited good activity against CRE (95.8% susceptible). Ceftolozane-tazobactam showed good activity against Escherichia coli (95.7% S) and Klebsiella pneumoniae (92.8% S), but limited activity against Enterobacter cloacae species complex (75.9% susceptible). All (100.0%) carbapenemase (CBase)-producing CRE isolates were aztreonam-avibactam-susceptible while 77.4% were ceftazidime-avibactam-susceptible and 67.7% were meropenem-vaborbactam-susceptible. The most common CBases were KPC (41.7%), NDM (12.5%), and OXA-48 types (10.4%). Metallo-β-lactamases represented 23.5% of CBases and were identified in 16.7% of CREs. The most active agents against P. aeruginosa were ceftazidime-avibactam (95.7% susceptible), ceftolozane-tazobactam (94.8% susceptible), and tobramycin (91.5% susceptible). Piperacillin-tazobactam and meropenem were active against 81.4% and 82.5% of P. aeruginosa, respectively, and aztreonam-avibactam inhibited 78.6% of P. aeruginosa at ≤8 mg/L.

Humans↗

PubMed2004

Assessment of pathogen occurrences and resistance profiles among infected patients in the intensive care unit: report from the SENTRY Antimicrobial Surveillance Program (North America, 2001).

Originating from 25 selected intensive care units (ICUs) in North America, a total of 1,321 bacterial strains from blood, respiratory tract, urine and wound sites were processed at a central laboratory as part of the SENTRY Antimicrobial Surveillance Program (2001) to assess their occurrence rates and antimicrobial susceptibility profiles. The rank order of pathogens recovered was Staphylococcus aureus (24.1%), Pseudomonas aeruginosa (12.2%), Escherichia coli (10.1%), Klebsiella spp. (8.9%), Enterococcus spp. (7.2%), coagulase-negative staphylococci (7.0%) and Enterobacter spp. (7.0%). Although oxacillin resistance among S. aureus was 51.4%, no resistance was detected to vancomycin, linezolid and quinupristin/dalfopristin. The most active agents tested against P. aeruginosa were amikacin, cefepime, tobramycin, meropenem and piperacillin/tazobactam (3.1-13.0% resistance). Among agents tested against the Enterobacteriaceae, amikacin, cefepime, imipenem and meropenem showed greatest in vitro activity (0.0-3.4% resistance). Extended-spectrum beta-lactamase-producing phenotype rates were 11.2 and 16.2% in E. coli and Klebsiella spp., respectively. Linezolid was most active against enterococci (1.1% resistance; G2576U ribosomal mutation) whereas 28.4% of isolates were resistant to vancomycin. Cefepime and the carbapenems (imipenem or meropenem) for Gram-negative isolates and linezolid for Gram-positive isolates, provided the broadest spectrum of in vitro activity against contemporary ICU pathogens in North America.

Anti-Bacterial Agents↗

PubMed2005

Trends in antimicrobial susceptibility in UK centres: the MYSTIC Programme (1997-2002).

Trends in antimicrobial susceptibilities in three UK centres participating in the MYSTIC Programme were examined from 1997 to 2002. Isolates were tested using standard methodology to determine the susceptibility breakpoints of meropenem and several other antimicrobial agents including imipenem, ceftazidime, piperacillin/tazobactam, ciprofloxacin and gentamicin. Data are grouped in 2-year blocks. The carbapenems were the most active agents tested against the Enterobacteriaceae (99-100% and 98-100% susceptibility to meropenem and imipenem, respectively) and non-fermenters, including Pseudomonas spp. and Acinetobacter spp. With the exception of susceptibility to ciprofloxacin, which decreased among Enterobacteriaceae at the end of the 6-year period, all antibiotics tested retained their levels of activity. The proportion of extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae increased during the study (4.8% and 11.3% in 1997-1998; 7.4% and 16.7% in 2001-2002, respectively). Both meropenem and imipenem retained their potency against these ESBL- and AmpC-producing isolates (100% for all time periods). All the other antimicrobial agents tested had much lower susceptibility against these resistant isolates and this decreased further over the 6-year period, with the exception of tazobactam, which maintained its low levels. Although all antibiotics tested retained acceptable activity, the carbapenems remained the most active antimicrobial agents against Gram-negative bacteria, including ESBL- and AmpC-producing isolates.

Anti-Infective Agents↗

PubMed2026

Single unscreened carrier triggered ICU outbreak of a KPC-producing Klebsiella pneumoniae which acquired in vivo resistance to ceftazidime-avibactam, and cefiderocol.

BACKGROUND: Carbapenemase-producing Enterobacterales are a major cause of healthcare-associated outbreaks in intensive care units (ICUs), where unrecognized carriers can drive silent transmission. We report an ICU outbreak caused by KPC-producing Klebsiella pneumoniae and the within-host emergence of resistance to ceftazidime-avibactam and cefiderocol in the index case. METHODS: Four ICU patients with five K. pneumoniae isolates identified between July and August 2023 were investigated. Phenotypic, genomic and functional analyses were performed to determine the clonal relatedness of the isolates and elucidate the mechanisms underlying resistance evolution. RESULTS: All isolates belonged to ST512, confirming dissemination of a single high-risk clone. The first isolate recovered from the index patient was susceptible to ceftazidime-avibactam and cefiderocol, but a later isolate obtained during ceftazidime-avibactam therapy acquired resistance to both agents. Genomic analysis revealed a novel KPC variant (KPC-270) carrying a 19-amino-acid duplication. When expressed in Escherichia coli, KPC-270 conferred ceftazidime-avibactam resistance, but it did not fully reproduce the meropenem or cefiderocol phenotype. Efflux inhibition substantially reduced meropenem and cefiderocol MICs in the resistant isolate, and avibactam partially restored cefiderocol activity, supporting multifactorial mechanism. CONCLUSION: This outbreak illustrates how unrecognized multidrug-resistant carriage in the index patient facilitated the nosocomial dissemination of a high-risk ST512 K. pneumoniae clone, followed by rapid resistance evolution during ceftazidime-avibactam therapy. Resistance was multifactorial, involving the novel KPC-270 variant and efflux activity contributing to ceftazidime-avibactam, meropenem and cefiderocol resistance.

Cefiderocol↗

PubMed2002

Geographic variations in activity of broad-spectrum beta-lactams against Pseudomonas aeruginosa: summary of the worldwide SENTRY Antimicrobial Surveillance Program (1997-2000).

With reports of increasing resistance to antimicrobial agents among Pseudomonas aeruginosa clinical isolates worldwide, the activities of cefepime and eight other broad-spectrum beta-lactams against 6969 isolates collected during 1997-2000 from the four regions of the SENTRY Antimicrobial Surveillance Program. P. aeruginosa isolates were tested by the reference broth microdilution method against nine beta-lactam antimicrobial agents (aztreonam, cefepime, ceftazidime, imipenem, meropenem, piperacillin +/- tazobactam, ticarcillin +/- clavulanate), three aminoglycosides (amikacin, gentamicin, tobramycin), and two fluoroquinolones (ciprofloxacin, levofloxacin). The strains were contributed by more than 100 medical centers. National Committee for Clinical Laboratory Standards criteria were used to identify susceptible and resistant isolates. P. aeruginosa strains from Latin America were generally the most resistant to all classes of antimicrobials, compared with strains from other regions. The beta-lactams exhibited a wide range of potency, with carbapenems most active (meropenem, 80-91% susceptible; imipenem, 76-88% susceptible). Piperacillin/tazobactam was the most active penicillin (77-80% susceptible), and cefepime (67-83% susceptible) had an average 2% (range, 0.7-3.5%) greater susceptibility rate than ceftazidime (66-80% susceptible) across all regions. The rank order of beta-lactam activity according to percent resistant isolates in North American P. aeruginosa strains was: meropenem (4.8% resistant) > cefepime (6.8%) > imipenem (8.6%) > piperacillin/tazobactam (10.3%) > piperacillin (12.9%). Only 2.3% and 6.5% of isolates were resistant to amikacin or tobramycin, respectively, and nearly 16% of P. aeruginosa strains were resistant to ciprofloxacin. Compared with other geographic regions, strains of P. aeruginosa remain most susceptible in North America. In all regions, aminoglycosides in combination with carbapenems, cefepime, or piperacillin/tazobactam would provide more potential antipseudomonal activity than fluoroquinolone combinations for wide-spectrum empiric regimens.

Aminoglycosides↗

PubMed1998

Clinical strategies for serious infection: a North American perspective.

In the United States, as in Europe, clinical strategies for serious infection are being increasingly driven by growing numbers of cephalosporin-resistant and multiresistant gram-negative bacilli. In a survey of nearly 400 hospital intensive care units in North America, resistance rates of Klebsiella to third-generation cephalosporins increased (from 3.6 to 14.4%) between 1990 and 1993. Resistance rates in Enterobacter are even higher, approaching 40%. Much of this resistance, which is due mainly to production of type-1 and extended spectrum beta-lactamases, appears to have arisen through overuse of third-generation cephalosporins and from poor hand-washing practices. In some American cities, a major reservoir of resistant organisms are nursing homes, where there is evidence of overuse of oral antibiotics. Currently, the most reliable agents available for the treatment of resistant gram-negative pathogens are the carbapenems, imipenem/cilastatin and meropenem, and the aminoglycoside, amikacin. A recent clinical study of meropenem monotherapy in patients with nosocomial pneumonia showed statistically significantly better clinical and microbiologic outcome compared with a standard regimen of ceftazidime plus tobramycin. The enhanced in vitro activity of meropenem against a number of key organisms may have been responsible for the superior results. Although the newer cephalosporins, cefepime and cefpirome, show greater stability to chromosomal type-1 beta-lactamases than ceftazidime, they have variable activity against extended spectrum beta-lactamase producers and can be rendered ineffective by permeability changes which occur in certain organisms. Carbapenems, on the other hand, possess good activity against virtually all of the pathogens which produce the clinically important beta-lactamases, and represent a reliable option for treatment.

Critical Illness↗

PubMed1999

In vitro activity of ciprofloxacin, levofloxacin, and trovafloxacin, alone and in combination with beta-lactams, against clinical isolates of Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Burkholderia cepacia.

We tested three fluoroquinolones (ciprofloxacin, levofloxacin, and trovafloxacin), each combined with each of four beta-lactams (cefoperazone, ceftriaxone, imipenem, and meropenem) for synergy against clinical isolates of nosocomial strains of Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Burkholderia cepacia. The ciprofloxacin-beta-lactam combinations showed synergy against none or only a small fraction (7 to 10%) of the P. aeruginosa and B. cepacia isolates. Ciprofloxacin-cefoperazone, -ceftriaxone, and -meropenem were synergic against 50%, 25%, and 30% of the S. maltophilia isolates, respectively. Among the levofloxacin combinations, only those with cefoperazone and imipenem showed significant synergy, and this only against B. cepacia (50% and 30%, respectively). Trovafloxacin-cefoperazone and -imipenem showed modest synergy against P. aeruginosa (23% and 27%, respectively), as did trovafloxacin-cefoperazone and -ceftriaxone against B. cepacia (30%). The trovafloxacin-imipenem combination was synergic against all isolates of B. cepacia. Because of their synergy, the following combinations may be useful in the nosocomial setting: trovafloxacin-cefoperazone or -imipenem against P. aeruginosa; ciprofloxacin-cefoperazone, -ceftriaxone, or -meropenem against S. maltophilia; levofloxacin-cefoperazone and trovafloxacin-imipenem against B. cepacia.

Anti-Infective Agents↗

PubMed2001

In-vitro activities of various antibiotics, alone and in combination with amikacin against Pseudomonas aeruginosa.

The in-vitro activities of various antibiotics, either alone or in combination with amikacin were assessed using clinical isolates of Pseudomonas aeruginosa. The minimum inhibitory concentrations (MIC) of these antibiotics were determined by microbroth dilution method against 50 clinical strains. The MIC values showed that 96, 94, and 74% of the isolates were susceptible or moderately susceptible to amikacin, meropenem and ceftazidime, respectively. The in vitro activities of ceftazidime and meropenem in combination with amikacin were determined by microbroth chequerboard technique and results were interpreted using the fractional inhibitory concentration (FIC) index. With a FIC index of < or =0.5 as borderline, synergistic interactions were more frequent with ceftazidime (70.8%) than with meropenem (40%). No antagonism was observed.

Amikacin↗

PubMed2002

Carbapenem-resistant Acinetobacter and role of curtains in an outbreak in intensive care units.

Multiple-antibiotic-resistant Acinetobacter baumanii, including meropenem resistance, was first isolated from a patient in the general intensive care unit of a tertiary-referral university teaching hospital in Birmingham in December 1998. Similar strains were subsequently isolated from 12 other patients, including those on another intensive care unit within the hospital. The outbreak followed an increase in the use of meropenem in both the units. Environmental screening revealed the presence of the multiple-resistant Acinetobacter species on fomite surfaces in the intensive care unit and bed linen. The major source appeared to be the curtains surrounding patients' beds. Typing by pulsed field gel electrophoresis demonstrated that the patients' isolates and those from the environment were indistinguishable. Rigorous infection control measures including increased frequency of cleaning of the environment with hypochlorite (1000 ppm) and twice-weekly changing of curtains were implemented, along with restriction of meropenem use in the units. Isolation of the multiple-resistant Acinetobacter spp. subsequently diminished and it was not detected over a follow-up period of 18 months. To our knowledge, this is the first reported outbreak of carbapenem-resistant Acinetobacter spp. from the UK. This outbreak also highlights environmental sources, particularly dry fabrics such as curtains, as an important reservoir for dissemination of acinetobacters.

Acinetobacter↗

PubMed2006

Prevalence and antibiotic susceptibility of Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae in Estonian intensive care units in comparison with European data.

This prospective cohort study was performed from April to December 2003 for the purpose of collecting a maximum of 50 non-duplicate isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae from each of 4 ICUs to determine minimum inhibitory concentrations. The most prevalent species were Enterobacteriaceae (13%), K. pneumoniae and A. baumannii (both 12%). 60% of A. baumannii strains were susceptible to ampicillin/sulbactam and cefepime, 95% to meropenem and imipenem, and 75% to amikacin. 79% of P. aeruginosa strains were piperacillin/tazobactam, 58% ceftazidime, 81% meropenem, 72% imipenem, 69% ciprofloxacin and 97% amikacin susceptible. The susceptibility of K. pneumoniae to meropenem and imipenem was 99%, to ciprofloxacin was 91% and to amikacin was 98%. Gram-negative bacteria (especially K. pneumoniae and A. baumannii) were prevalent in our ICUs compared to other European studies. Carbapenem susceptibility of Estonian strains was higher, but P. aeruginosa sensitivity to ceftazidime was lower, compared to other EU countries.

Acinetobacter Infections↗

PubMed1995

Differences in therapeutic efficacy among cell wall-active antibiotics in a mouse model of gram-negative sepsis.

The in vivo efficacy of three cell wall-active antibiotics, imipenem, meropenem, and ceftazidime, was compared in mice rendered hypersusceptible to the pathophysiologic effects of lipopolysaccharide by treatment with D-galactosamine. When CF-1 mice were administered Escherichia coli, D-galactosamine, and saline intraperitoneally, an LD50 was achieved at an inoculum of approximately 2 x 10(4) cfu. Administration of antibiotic at 20 mg/kg resulted in significant but widely variable protective efficacy from E. coli lethality among the three antibiotics. At this dose, an approximately 3-fold increase in LD50 was observed with either meropenem or ceftazidime, whereas administration of imipenem resulted in an approximately 8-fold increase in LD50 (P = .0053). When the dose of antibiotic was decreased to 2 mg/kg, neither meropenem nor ceftazidime could provide measurable protection, whereas imipenem was almost fully protective (P < .002). These differences in protective efficacy were also noted with experimental Pseudomonas aeruginosa but not Staphylococcus aureus infection.

Animals↗

PubMed1992

Inactivation of new carbapenem antibiotics by dehydropeptidase-I from porcine and human renal cortex.

The stability of the new carbapenem antibiotics, panipenem, meropenem and LJC 10,627, against porcine and human renal dehydropeptidase-I (DHP-I) was compared with that of imipenem. The order of stability to hydrolysis by renal DHP-I was: LJC 10,627 greater than meropenem greater than panipenem greater than imipenem. After incubation of the drugs with porcine or human enzyme at 30 degrees C for 4 h, the percentages of residual activity were as follows: LJC 10,627, 73.7% and 95.6%, respectively; meropenem, 0.2% and 28.7%, respectively; panipenem, 0% and 4.3%, respectively; and imipenem, 0% and 0.1%, respectively. These results demonstrate that LJC 10,627 has extremely high stability against renal DHP-I.

Animals↗