SEARCH · PubMed Health

Results for “Meropenem”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources

PubMed1992

beta-Lactamase production and susceptibility of US and European anaerobic gram-negative bacilli to beta-lactams and other agents.

The susceptibility of 1,476 US and European strains of anaerobic gram-negative bacilli to amoxicillin, amoxicillin/clavulanate, ticarcillin, ticarcillin/clavulanate, cefoxitin, imipenem and metronidazole was determined. All of the Bacteroides fragilis group and 51% of the non-Bacteroides fragilis group were beta-lactamase positive. Amongst the non-Bacteroides fragilis group, beta-lactamase positivity rates were higher for US strains (58%) than for European strains (39%). All strains were susceptible to imipenem and metronidazole. MIC90s of amoxicillin and ticarcillin for all beta-lactamase negative strains were 0.5 and 2 micrograms/ml, respectively. The addition of clavulanate reduced the MIC90s of amoxicillin (> or = 256 micrograms/ml) and ticarcillin (> or = 64 micrograms/ml) to 16 and 8 micrograms/ml, respectively, for the Bacteroides fragilis group, and to 4 micrograms/ml for both agents for the non-Bacteroides fragilis beta-lactamase producing group. Twenty-nine cefoxitin-resistant strains were found, mainly in the Bacteroides fragilis group, while 95 beta-lactamase producing strains (predominantly Bacteroides fragilis group and fusobacteria) did not show synergy between beta-lactams and clavulanate. Of the newe agents tested, meropenem and piperacillin-tazobactam were the most active (100% of strains susceptible), followed by amoxicillin-BRL 42715 (99% of strains susceptible); 94 to 98% of the strains were susceptible to cefoperazone-sulbactam, tosufloxacin, temafloxacin and clindamycin. Only 73% of the strains were susceptible to cefotetan, compared to 91% to cefoxitin; 88% of the strains were susceptible to trospectomycin. Overall, all of the beta-lactam/beta-lactamase inhibitor combinations, imipenem, meropenem, cefoxitin, tosufloxacin, temafloxacin and clindamycin had good activity against beta-lactamase producing strains, while all agents tested had good activity against beta-lactamase negative strains.

Anti-Bacterial Agents↗

PubMed1992

In vitro activity of L-627 against anaerobic bacteria.

The in vitro activity of L-627 against 370 anaerobic bacterial strains including anaerobic cocci, Propionibacterium acnes, Clostridium perfringens, Clostridium difficile, Bacteroides fragilis, other Bacteroides spp. and fusobacteria was determined by the agar dilution method. This activity was compared with that of piperacillin, cefoxitin, imipenem, meropenem, clindamycin, metronidazole and chloramphenicol. L-627, imipenem, meropenem, clindamycin, metronidazole and chloramphenicol were the most active agents tested. L-627 had in vitro activity similar to that of the other carbapenems tested.

Anti-Bacterial Agents↗

PubMed2004

Screening for highly active beta-lactam antibiotics against Agrobacterium tumefaciens.

Quantitative in vitro antibacterial activities, i.e., minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs), of 12 beta-lactam antibiotics against Agrobacterium tumefaciens strains LBA4404 and EHA101 were examined, in order to identify antibiotics effective in eliminating the bacteria in Agrobacterium-mediated plant genetic transformation. The antibacterial activities of beta-lactams tested against strain EHA101 were equal to or less than those tested against strain LBA4404. Cefotaxime, cefbuperazone, and meropenem had high activities against strain LBA4404 (MBC <1 mg l(-1)). Against strain EHA101, however, only meropenem showed activity comparable to that against strain LBA4404. The production of beta-lactamase was observed only in strain EHA101.

Agrobacterium tumefaciens↗

PubMed2004

Rates of antimicrobial resistance among common bacterial pathogens causing respiratory, blood, urine, and skin and soft tissue infections in pediatric patients.

Antimicrobial resistance patterns among the principal bacterial pathogens from infections of the respiratory tract, blood, skin and soft tissue, and urinary tract of pediatric patients from the USA, Canada, Germany, France, and Italy were studied using the The Surveillance Network (TSN) database. Among Streptococcus pneumoniae isolates from respiratory tract infections, the prevalence of high-level penicillin resistance (MIC>/=2 microg/ml) ranged from 1.1 (Italy) to 36.2% (USA); erythromycin resistance was higher, ranging from 13.4 (Germany) to 63.8% (France). The prevalence of beta-lactamase-positive Haemophilus influenzae among isolates from lower respiratory tract infections ranged from <10 (Italy and Germany) to 38.4% (USA). Among isolates from blood and skin and soft tissue infections, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) ranged from 7.2% (Canada and Germany) to 27.3% (Italy). The prevalence of Escherichia coli and Klebsiella pneumoniae with putative extended-spectrum beta-lactamases among isolates from blood, urinary tract, and skin and soft tissue infections ranged from 0 (Germany and France) to 29.6% (Italy). With the exception of pseudomonal infections or infections with MRSA, amoxicillin-clavulanate retained moderate activity, whilst ceftriaxone and cefepime were the most effective broad-spectrum injectable agents. Meropenem was the most effective agent against Pseudomonas aeruginosa with <5% resistance. Low levels of resistance, along with acceptable safety profiles and the availability of convenient oral formulations, continue to support the use of ceftriaxone, cefepime, amoxicillin-clavulanate, and meropenem as viable options for the treatment of infections in pediatric patients.

Anti-Bacterial Agents↗

PubMed2005

An epidemiological study of the susceptibility and frequency of multiple-drug-resistant strains of Pseudomonas aeruginosa isolated at medical institutes nationwide in Japan.

The susceptibility of 3233 strains of Pseudomonas aeruginosa, isolated primarily in 2001, as agents of infection at 37 medical institutes with various specialties in seven regions of Japan (ranging from Hokkaido to Kyushu/Okinawa), to 18 antipseudomonal agents known to be active against P. aeruginosa was evaluated, in accordance with the National Committee for Clinical Laboratory Standards (NCCLS) guidelines. Of the 18 antipseudomonal agents, including some combinations of beta-lactamase inhibitors and antibacterial agents, ciprofloxacin had the lowest minimum inhibitory concentration (MIC)(50) (0.25 microg/ml) against P. aeruginosa, followed by meropenem, with an MIC(50) of 0.5 microg/ml. The MIC(50) of 7 of the examined antibacterial agents (ceftazidime, cefozopran, imipenem, biapenem, gentamicin, tobramycin, and levofloxacin) was between 1 and 2 microg/ml. Among the antipseudomonal agents tested, tobramycin showed the lowest MIC(90) (2 microg/ml), which was not significantly different from its MIC(50) (1 microg/ml). The MIC(90) of the other antibacterial agents examined ranged from 8 to 64 microg/ml and more. The susceptibility of the 3233 strains to the 12 antibacterial agents covered by the NCCLS guidelines was determined according to the standard method of the NCCLS guidelines. The frequency of strains resistant to meropenem, gentamicin, or tobramycin was relatively low (7.5%-8.3%). The frequency of strains showing intermediate to severe resistance to tobramycin was particularly low (8.0%). The frequency of strains resistant to aztreonam, imipenem, or levofloxacin was 16.7%-19.0%, about twice as high as the frequency of strains resistant to tobramycin. The susceptibility pattern of the 3233 strains (isolated from seven regions of Japan) to five antibacterial agents (ceftazidime, piperacillin, imipenem, gentamicin, and ciprofloxacin) was evaluated in relation to the regions from which they were isolated. The MIC(50) values of these antibacterial agents did not differ significantly among the regions. However, the MIC(90) values of ceftazidime and gentamicin were higher for strains isolated from the Kansai region than for strains isolated from other regions. The MIC(90) of ciprofloxacin was higher for strains isolated from the Tohoku, Kansai, and Kyushu/Okinawa regions than for strains isolated from other regions. Of the 3233 strains, 89 were classified as multiple-drug-resistant (imipenem, gentamicin, and ciprofloxacin) strains. Of these 89 strains, 42 were isolated from urine, 17 from sputum or pharyngeal mucus, 13 from pus, 8 from blood, 1 from cerebrospinal fluid, and 8 from other specimens. The frequency of multiple-drug-resistant strains was higher among strains isolated from the Tohoku and Kansai regions than in strains isolated from other regions.

Cerebrospinal Fluid↗

PubMed2006

Bactericidal activities of parenteral antibiotics and genotype of penicillin-binding protein in Streptococcus pneumoniae and Haemophilus influenzae isolated from children's blood.

A total of 16 isolates of Streptococcus pneumoniae and 18 isolates of Haemophilus influenzae were obtained from the blood of children admitted to the pediatric wards of hospitals in Hokkaido Kamikawa subprefecture between January 2003 and December 2005. The ages of the patients with S. pneumoniae or H. influenzae infection ranged from 2 months to 9 years and from 1 month to 4 years, respectively. The diagnoses of S. pneumoniae infection were as follows: pneumonia in 8 patients, occult bacteremia in 5 patients, and meningitis in 3 patients. The diagnoses of H. influenzae were: meningitis in 6 patients, pneumonia in 4 patients, occult bacteremia in 4 patients, epiglotitis in 2 patients, and facial cellulitis in 2 patients. Out of 16 S. pneumoniae isolates, penicillin-resistant strains with a mutation of 3 genes were observed in 7 children, and penicillin intermediate-resistant strains with a mutation of 1 or 2 genes were observed in 8 children. Out of 18 H. influenzae isolates, the beta-lactamase-negative ampicillin-resistant strain with a substitution of 2 points in the ftsI gene was revealed in 2 children, the beta-lactamase-negative ampicillin-resistant strain with a substitution of 1 point in the ftsI gene was observed in 4 children, the beta-lactamase-positive amoxicillin/clavulanic acid-resistant strain with blaTEM-1 and ftsI with 2 substitutions in the ftsI gene was observed in 3 children, and the beta-lactamase-positive ampicillin-resistant strain with blaTEM-1was not observed. The MBC90s of ampicillin, ceftriaxone, cefotaxime, meropenem, panipenem, and vancomycin against S. pneumoniae were 8 microg/ml, 1 microg/ml, 1 microg/ml 1 microg/ml, 0.25 microg/ml, and 0.5 microg/ml, respectively. Those of ampicillin, piperacillin, ceftriaxone, cefotaxime, meropenem, and panipenem against H. influenzae were >128 microg/ml, >128 microg/ml, 0.25 microg/mL, 1 microg/ml, 0.12 microg/ml, and 0.5 g/ml, respectively. It is suggest that the minimum bactricidal concentration (MBC) was dissociated from the minimum inhibitory concentration (MIC) in S. pneumoniae and H. influenzae with abnormal pbp genes.

Ampicillin Resistance↗

PubMed1999

Activities of beta-lactams, fluoroquinolones, amikacin and fosfomycin alone and in combination against Pseudomonas aeruginosa isolated from complicated urinary tract infections.

Using the checkerboard titration method as well as the time-kill curve technique, we investigated the activities of beta-lactams, fluoroquinolones, amikacin, and fosfomycin alone and in combination against Pseudomonas aeruginosa isolated from patients with complicated urinary tract infections. In the checkerboard titration studies, none of 21 combinations demonstrated antagonism against 26 strains tested, and the mean fractional inhibitory concentration (FIC) indices for these combinations ranged between 0.4694 and 0.9828. Corresponding to the respective FIC indices, the bactericidal activity determined in combinations of meropenem with ciprofloxacin or amikacin and ceftazidime with ciprofloxacin at sub-minimum inhibitory concentrations (MICs) produced a great reduction in bacterial counts (>/=2 log10 CFU/ml) within 6 h of administration against most of the strains, including strains resistant to one or both drugs, and these synergistic effects were confirmed morphologically by scanning electron microscopy. In time-lag combinations, the first administration of ciprofloxacin or amikacin supplemented by meropenem with 1-h lag diminished bactericidal activity, in comparison with the simultaneous administration of the drugs. These results suggest that simultaneous combinations of beta-lactams with fluoroquinolones or amikacin may be useful alternatives for the treatment of serious infections due to P. aeruginosa.

Journal Article↗

PubMed2001

Survey of antibiotic resistance in Pseudomonas aeruginosa by The Tokyo Johoku Association of Pseudomonas Studies.

Pseudomonas aeruginosa resistance (minimum inhibitory concentration [MIC], > or =16 microg/ml defined as resistant) to meropenem, imipenem, panipenem, piperacillin, ceftazidime, cefozopran, cefoperazone, sulbactam/cefoperazone, amikacin, and tobramycin, as well as cross-resistance profiles, were investigated in P. aeruginosa strains isolated at eight hospitals in the Johoku area, Tokyo, during November 1998. Overall, 8.3% of isolates were imipenem-resistant and 4.6% were ceftazidime-resistant. However, the incidence of antibiotic-resistant P. aeruginosa was distinctly different at each hospital. P. aeruginosa resistance to imipenem ranged from (MIC) 1 to 64 microg/ml (MIC90 32 microg/ml), and its resistance to ceftazidime ranged from 2 to more than 128 microg/ml (MIC90, 64 microg/ml). Meropenem (MIC range, < or =0.25 to 16 microg/ml) was more active than panipenem (MIC range, 2 to 64 microg/ml). Cefozopran was more active than piperacillin, cefoperazone, or sulbactam/cefoperazone, but many strains were resistant to cefoperazone (17/57). Our analysis found cross-resistance to many beta-lactams, but the degree of cross-resistance was very variable.

Anti-Bacterial Agents↗

PubMed2004

Pharmacodynamic comparisons of antimicrobials against nosocomial isolates of escherichia coli, klebsiella pneumoniae, acinetobacter baumannii and pseudomonas aeruginosa from the MYSTIC surveillance program: the OPTAMA Program, South America 2002.

The OPTAMA (Optimizing Pharmacodynamic Target Attainment using the MYSTIC [Meropenem Yearly Susceptibility Test Information Collection] Antibiogram) Program provides insight into the appropriate antibiotic options for empiric therapy for common nosocomial pathogens. In this report, South America is represented by Brazil, Colombia, Peru, and Venezuela. A 5000-subject Monte Carlo Simulation estimated pharmacodynamic target attainment for meropenem, imipenem, ceftazidime, cefepime, piperacillin/tazobactam, and ciprofloxacin against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Pharmacokinetic parameter variability was derived from existing healthy volunteer data, and minimum inhibitory concentration (MIC) data came from the 2002 MYSTIC program. Piperacillin/tazobactam and ciprofloxacin displayed the lowest target attainment against all bacterial species (14% to 24% for A. baumannii, 26% to 37% for P. aeruginosa, and 48% to 66% for the Enterobacteriaceae). Overall, the carbapenems had the highest probabilities of attainment against the Enterobacteriaceae (98% to 100%) and A. baumannii (73% to 74%), whereas cefepime obtained the greatest target attainment against P. aeruginosa (65%). Because no single regimen had high target attainment against A. baumannii and P. aeruginosa, the use of combination therapy to treat these pathogens in South America may be justified. Because of the lack of agreement with percent susceptibility for certain antimicrobial regimens, the use of pharmacodynamic target attainment may be a more accurate predictor of microbiologic success.

Acinetobacter baumannii↗

PubMed2005

Comparative activity of doripenem and three other carbapenems tested against Gram-negative bacilli with various beta-lactamase resistance mechanisms.

Doripenem (formerly S-4661), a novel carbapenem antimicrobial, was compared with ertapenem, imipenem, and meropenem using reference broth microdilution test methods against wild-type and various resistant microbial subsets (380 strains). Doripenem and meropenem were consistently more potent than ertapenem or imipenem when tested against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. Ertapenem exhibited minimum inhibitory concentration (MIC) elevations for some isolates producing AmpC and extended-spectrum beta-lactamases, in contrast to greater enzyme stability for doripenem and other carbapenems tested. Multiple beta-lactamase (TEM, SHV, CTX-M, OXA, CMY types)-producing Escherichia coli had doripenem MIC values at </=0.016 mug/mL (with higher values for ertapenem). Doripenem appears to be a promising, potent carbapenem for parenteral use against contemporary Gram-negative bacilli producing various beta-lactamases.

Anti-Bacterial Agents↗

PubMedDate not supplied

Extended spectrum beta-lactamase-producing Klebsiella pneumoniae chronic ambulatory peritoneal dialysis peritonitis treated successfully with polymyxin B.

Peritonitis is not an infrequent complication of inpatients with chronic ambulatory peritoneal dialysis (CAPD). CAPD peritonitis may be related to the catheter or secondary to perforation of an intra-abdominal viscus. The most common organisms usually associated with CAPD peritonitis are Staphylococcus aureus and Staphylococcus epidermidis (coagulase-negative staphylococci). Rarely, aerobic gram-negative bacilli have been the causative agents of CAPD peritonitis. The treatment of CAPD peritonitis usually requires removal of the peritoneal catheter and treatment with parenteral antibiotics active against the causative pathogen. We report a case of CAPD-associated peritonitis caused by an extended spectrum beta-lactamase-producing strain of Klebsiella pneumoniae. The case presented had this strain of multidrug-resistant K. pneumoniae present in blood cultures and the peritoneal fluid. Extended spectrum beta-lactamase-producing bacteria, for example, K. pneumoniae, are multidrug-resistant and sensitive to few antibiotics. This isolate was intermediately sensitive to amikacin and meropenem, but the patient did not clinically improve on these 2 antibiotics. Polymyxin B therapy was initiated after lack of clinical improvement after dialysis catheter removal and 1 week of meropenem and amikacin therapy. The patient responded rapidly to therapy with polymyxin B. Polymyxin B has a unique mechanism of action on bacterial cells and is highly active against all multidrug-resistant gram-negative organisms except Proteus species and Serratia marcescens. No toxicity was observed during therapy. Polymyxin B is being used increasingly as a therapeutic alternative to multidrug-resistant gram-negative organisms.

Adult↗

PubMed2004

Antimicrobial resistance among non-fermentative Gram-negative bacilli isolated from the respiratory tracts of Italian inpatients: a 3-year surveillance study by the Italian Epidemiological Survey.

The Italian Epidemiological Survey evaluated antibiotic susceptibility of non-fermentative Gram-negative bacilli isolated from inpatient respiratory-tract specimens collected throughout Italy during 1997-1999. The minimal inhibitory concentrations of 14 antibiotics for 1474 Pseudomonas aeruginosa strains, 307 Stenotrophomonas maltophilia strains and 114 Acinetobacter baumannii strains were determined in 57 clinical microbiology laboratories by means of a standardised micro-dilution method. The most active drugs against P. aeruginosa isolates were meropenem (81% susceptible) and amikacin (80% susceptible). Imipenem and meropenem proved to be the only agents active against A. baumannii isolates, although 13 and 16%, respectively, of strains were resistant to these drugs. Trimethoprim-sulphamethoxazole (TMP-SMZ) showed activity only against S. maltophilia isolates (83% susceptible). A total of 185 multidrug-resistant P. aeruginosa isolates (resistant to piperacillin, ceftazidime, gentamicin, and imipenem) were found. Resistance rates and trends showed consistent regional variations, including sharp increases from 1997 to 1999 in imipenem resistance among P. aeruginosa isolates from central and southern Italy.

Acinetobacter Infections↗

PubMed2004

In vitro activity of parenteral Beta-lactams, levofloxacin and tobramycin alone or in combination against extended-spectrum Beta-lactamase producing Klebsiella pneumoniae.

MICs and time-kill studies were performed for four clinical isolates of extended-spectrum Beta-lactamase (ESBL)-producing Klebsiella pneumoniae. MICs (mg/L) were: piperacillin/tazobactam 8, cefepime 1-2, meropenem 0.03-0.06, levofloxacin 0.5-8 and tobramycin 0.25-32. For monotherapy, only meropenem maintained bactericidal activity over the 24 h for all isolates. Levofloxacin and tobramycin maintained bactericidal activity against the isolate susceptible to each drug. Piperacillin/tazobactam and cefepime did not maintain bactericidal activity against any isolate. Combination therapy with piperacillin/tazobactam or cefepime combined with levofloxacin or tobramycin were able to provide dramatic killing against ESBL K. pneumoniae, but did not always maintain bactericidal activity. Future studies should evaluate different antimicrobial combinations against pathogens producing specific ESBL enzymes to define their utility as an alternative to carbapenems.

Drug Therapy, Combination↗

PubMed2004

Effective antibiotic regime for postoperative acute cholangitis in biliary atresia--an evolving scene.

PURPOSE: The prompt use of empirical antibiotics is vital in managing post-Kasai cholangitis. The authors published findings of their clinical trial in 1991 and established the use of cefoperazone, with a response rate of 88.9%. Here its clinical use since its introduction is reviewed and the trend in its efficacy is assessed. METHODS: A retrospective review was carried out between 1997 and 2003. All episodes of acute cholangitis in patients who underwent Kasai procedure were recorded. Cholangitis was defined as unexplained fever with derangement of liver enzymes. Cefoperazone was started empirically according to the established protocol, and the response to treatment was analyzed. RESULTS: There were 19 patients with a total of 49 episodes of cholangitis. Cefoperazone was used as the first-line empirical antibiotic in 40 of these episodes. Only 30 showed successful response (75%). For the 10 unresponsive episodes, meropenem was used as second-line antibiotic with complete response in all. CONCLUSIONS: The efficacy of cefoperazone in the treatment of post-Kasai cholangitis has decreased over the last years. This suggests a need for a more effective first-line empirical antibiotic. From this review, meropenem seems to be a suitable candidate, and a future prospective clinical trial is warranted.

Acute Disease↗

PubMed2006

Resistance to antibiotics in clinical isolates of Pseudomonas aeruginosa.

OBJECTIVES: To analyse the global resistance to some antibiotics used to treat nosocomial infections by Pseudomonas aeruginosa, specially to carbapenems, and its relationship with the presence of carbapenemases, OXA, VIM and IMP. METHODS: The study included 229 P. aeruginosa isolates from a Hospital in Northern Spain (year 2002). Susceptibility to antimicrobial agents was determined by the analysis of the MIC. Genetic typing was carried out by RAPD-PCR fingerprinting with primer ERIC-2. Genetic experiments to detect class-1 integrons were performed by PCR with primers 5'CS and 3'CS. Detection of carbapenemases was done by phenotypic (Hodge test and DDST) and genotypic methods (PCR with primers for imp, vim1, vim2 and oxa40 genes). RESULTS: 23.9% of isolates were resistant to ceftazidime, 35.9% to cefotaxime, 5.3% to amikacin, 54.9% to gentamicin, 14.6% to imipenem and 6.6% to meropenem. Isolates resistant to imipenem (33) were furtherly tested. Genetic typing didn't show clonal relatedness among the most of the isolates. Class-1 integrons were present in most isolates (sizes 600-1700 bp). Phenotypic methods for carbapenemases showed 5 positive isolates. Genotypic methods showed the presence of two isolates with the oxa40 gene. CONCLUSIONS: Meropenem, amikacin and imipenem were the most active agents to treat infections caused by Pseudomonas aeruginosa. In our study, the presence of carbapenemase enzymes wasn't high. Phenotypic tests cannot be considered as accurate screening tool to detect carbapenemases. This is the fist report of the oxa40 gene in Pseudomonas aeruginosa isolates.

Anti-Bacterial Agents↗

PubMed2000

Antimicrobial resistance in Burkholderia pseudomallei.

Four strains of Burkholderia pseudomallei were used to determine the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill curves with 13 single antimicrobial agents: ceftazidime, piperacillin, imipenem, amoxicillin/clavulanic acid, doxycycline, cotrimoxazole, kanamycin, rifampicin, ciprofloxacin, trovafloxacin, clarithromycin, azithromycin and meropenem. The time-kill studies were also performed with 33 pairs of combinations of the above antimicrobial agents: 15 combinations which would be expected to be used for acute therapy and 18 combinations for maintenance therapy. The results show that the single and combination antimicrobial agents with bactericidal effects against the four strains of B. pseudomallei which should be used for clinical trials in acute melioidosis are: imipenem, meropenem, and imipenem + azithromycin. The combination antimicrobial agents which should be further studied for the ability to eliminate biofilm and intracellular killing effect are ciprofloxacin + clarithromycin, ciprofloxacin + azithromycin, and imipenem + azithromycin.

Anti-Bacterial Agents↗

PubMed2001

Nosocomial pneumonia. Diagnostic and therapeutic considerations.

Many patients with presumed nosocomial pneumonia probably have infiltrates on the chest radiograph, fever, and leukocytosis resulting from noninfectious causes. Because of the high mortality and morbidity associated with nosocomial pneumonias, however, most clinicians treat such patients with a 2-week empiric trial of antibiotics. Before therapy is initiated, the clinician should rule out other causes of pulmonary infiltrates, fever, and leukocytosis that mimic a nosocomial pneumonia (e.g., pre-existing interstitial lung disease, primary or metastatic lung carcinomas, pulmonary emboli, pulmonary drug reactions, pulmonary hemorrhage, collagen vascular disease affecting the lungs, or congestive heart failure). If these disorders can be eliminated from diagnostic consideration, a 2-week trial of empiric monotherapy is indicated. The clinician should treat cases of presumed nosocomial pneumonia as if P. aeruginosa were the pathogen. Although P. aeruginosa is not the most common cause of nosocomial pneumonia, it is the most virulent pulmonary pathogen associated with nosocomial pneumonia. Coverage directed against P. aeruginosa is effective against all other aerobic gram-negative bacillary pathogens causing hospital-acquired pneumonia. The clinician should select an antibiotic for empiric monotherapy that is highly effective against P. aeruginosa, has a good side-effect profile, has a low resistance potential, and is relatively inexpensive in terms of its cost to the institution. The preferred agents for empiric monotherapy for nosocomial pneumonia are cefepime, meropenem, and piperacillin. Single organisms are responsible for nosocomial pneumonia, not multiple pathogens. S. aureus rarely, if ever, causes nosocomial pneumonia but is mentioned frequently in studies based on cultures of respiratory tract secretions. S. aureus, unless accompanied by a necrotizing pneumonia with rapid cavitation within 72 hours, in the sputum indicates colonization rather than infection and should not be addressed therapeutically. Antibiotics associated with a high resistance potential should not be used as monotherapy or included in combination therapy regimens (i.e., ceftazidime, ciprofloxacin, imipenem, or gentamicin). Combination therapy is more expensive than monotherapy and is indicated only when P. aeruginosa is extremely likely, based on its characteristic clinical presentation, or is proved by tissue biopsy. Therapy should not be based on respiratory secretion cultures regardless of technique. Optimal combination regimens include cefepime or meropenem plus levofloxacin or piperacillin or aztreonam or amikacin. Nosocomial pneumonias usually are treated for 14 days. Lack of radiographic or clinical response to appropriate empiric nosocomial pneumonia monotherapy after 14 days suggests an alternate diagnosis. In these patients, a tissue biopsy specimen should be obtained to determine the cause of the persistence of pulmonary infiltrates unresponsive to appropriate antimicrobial therapy.

Anti-Bacterial Agents↗

PubMed1995

Carbapenems.

Carbapenems are broad-spectrum beta-lactam antibiotics that cover an absolute majority of all bacterial pathogens that possess a cell wall. The only clinically important exceptions are X. maltophilia, E. faecium, and some strains of methicillin-resistant staphylococci and penicillin-resistant pneumococci. So far, after several years of clinical use of imipenemcilastatin, emergence of resistance has been a problem mainly restricted to P. aeruginosa. The pharmacokinetics of carbapenems, especially imipenem, are complicated by the renal metabolism, necessitating the imipenem-cilastatin combination. This is not required for meropenem. The safety profile of carbapenems is favorable. With imipenem-cilastatin, nausea constitutes a practical problem in that administration times may have to be prolonged. The risk for neurologic reactions with imipenem-cilastatin has become a factor reducing the possibilities to use high doses. For all indications except bacterial meningitis, the now approved maximal dose of 4 g per day should suffice. In this respect, meropenem has an advantage over imipenem-cilastatin in that it can be used in the treatment of bacterial meningitis without apparent increased risk of seizures. Carbapenems are indicated mainly as empiric monotherapy in serious infections, such as intra-abdominal infections and infections in neutropenic patients. Combinations of carbapenems and other antibiotics should not be used routinely.

Animals↗