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PubMed2003

Confirmation of extended-spectrum beta-lactamase-producing Serratia marcescens: preliminary report from Taiwan.

Although Serratia marcescens is a common cause of nosocomial infection in Taiwan, strains producing extended-spectrum beta-lactamases (ESBLs) are rare. We detected four clinical isolates of S. marcescens from Taiwan that exhibited resistance to cefotaxime (MICs, > 256 microg/ml) and cefepime (MICs, > or = 32 microg/ml), but were susceptible to imipenem and meropenem. Transconjugants revealed similar MIC profiles when compared to the parental strains. Isoelectric focusing revealed one major transferable beta-lactamase (pI 8.4), which was further identified as CTX-M-3 by polymerase chain reaction and gene sequencing. An AmpC-like enzyme (pI 8.8) was not transferable. All four isolates had significant MIC reductions of > or =3 log(2) dilutions for cefepime in the presence of clavulanic acid, compatible with the presence of an ESBL (CTX-M-3). Clavulanate did not significantly reduce the cefotaxime MIC for one isolate that may co-produce high-level AmpC beta-lactamase (pI 8.8). Since high-level AmpC expression has minimal effect on the activity of cefepime, isolates co-producing AmpC beta-lactamase may be recognized as additional ESBL producers by using cefepime as an ESBL screening agent.

Anti-Bacterial Agents↗

PubMed2003

Occurrence and antimicrobial susceptibility patterns of pathogens isolated from skin and soft tissue infections: report from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 2000).

A total of 1,404 bacterial isolates were recovered from skin and soft tissue infections (SSTIs) from hospitalized patients in 24 sites in the United States (US) and 5 Canadian medical centers as part of the SENTRY Antimicrobial Surveillance Program. Isolates were collected between October and December, 2000. The rank order of pathogens was: Staphylococcus aureus (45.9%), Pseudomonas aeruginosa (10.8%), Enterococcus spp. (8.2%), Escherichia coli (7.0%), Enterobacter spp. (5.8%) and Klebsiella spp. (5.1%). The same order was observed in the US and Canada. Of note, almost 30% of S. aureus were oxacillin-resistant. Vancomycin resistance among enterococci was low (7.8%) representing a marked decrease from earlier SENTRY Program reports. Several antimicrobial agents remained very active against P. aeruginosa and Enterobacteriaceae isolates. In particular amikacin, cefepime, and the carbapenems (imipenem and meropenem) showed an excellent spectrum of activity (>95% susceptible). Extended-spectrum beta-lactamase production was observed in both E. coli (7.1%) and Klebsiella spp. (11.3%). Cefepime remained highly active, even against ceftazidime-resistant isolates of Enterobacter spp. The results of this study have identified the most common causes of SSTIs in hospitalized patients in North America, and can be used to make informed decisions concerning standards of empiric treatment for SSTIs in this region.

Anti-Bacterial Agents↗

PubMed2003

Global patterns of susceptibility for 21 commonly utilized antimicrobial agents tested against 48,440 Enterobacteriaceae in the SENTRY Antimicrobial Surveillance Program (1997-2001).

A total of 48,440 Enterobacteriaceae isolates collected consecutively from patients hospitalized in participant SENTRY Antimicrobial Surveillance Program sites in four international regions (Asia-Pacific, Europe, Latin America, and North America) were tested by reference broth microdilution method against the most commonly used antimicrobial agents. The most active compounds could be divided in 3 groups based on their spectrum of activity. The first group included meropenem and imipenem, with 99.9% susceptibilty (S) rates for the Enterobacteriaceae. The second group includes amikacin (97.3% S) and cefepime (97.2% S); and a third active group had a rank order of susceptibility of: gatifloxacin = levofloxacin (91.7% S) > ceftazidime (91.4% S) > ceftriaxone (91.2% S) > aztreonam (91.1% S) > gentamicin (90.6% S) > piperacillin/tazobactam = ciprofloxacin (90.5% susceptibility). These latter antimicrobial agents presented susceptibility rates of approximately 90% (89.8%-91.7%). Continued resistance surveillance by various programs remain necessary to monitor the in vitro effectiveness of antimicrobial agents currently used in clinical practice.

Anti-Bacterial Agents↗

PubMed1996

Phenotypic detection of mec A-positive staphylococcal blood stream isolates: high accuracy of simple disk diffusion tests.

Detection of oxacillin-resistance in staphylococci by phenotypic methods remains problematic. Although standardized susceptibility test methods are adequate for Staphylococcus aureus, many are less satisfactory for the coagulase-negative staphylococci (CNS). We have studied 108 consecutive blood culture isolates of staphylococci. The mec A gene was detected by PCR in one S. aureus and 55 CNS isolates. Susceptibility testing was performed as follows: oxacillin (1-microgram), ceftizoxime (30-microgram), and cephalothin (30-microgram) by disk diffusion; oxacillin, ceftizoxime, cephalothin, methicillin, ampicillin, ampicillin/ sulbactam, penicillin, cefazolin, imipenem, and meropenem by the broth microdilution method. In addition, isolates were tested by the oxacillin agar screen plate method. The single oxacillin-resistant S. aureus strain was detected by all oxacillin susceptibility test methods and by the ceftizoxime disk and MIC methods. Two oxacillin-susceptible S. aureus were intermediate (minor error) by ceftizoxime broth microdilution (MIC, 16 micrograms/mL). The most sensitive, simple phenotypic methods for detection of oxacillin-resistant CNS (mec A positive) were as follows: oxacillin disk diffusion at 98%, oxacillin screen plate at 91%, oxacillin broth microdilution at 87%, ceftizoxime disk diffusion at 100%, ceftizoxime broth microdilution at 87%, and methicillin broth microdilution at 83%. These results indicate that oxacillin and ceftizoxime disk diffusion tests are the most accurate phenotypic methods in routine clinical use for detection of oxacillin-resistant CNS. Oxacillin broth microdilution MIC testing (2% NaCl supplement) would perform more satisfactorily (100% sensitivity) with an adjusted interpretive breakpoint at < or = 0.5 microgram/mL, in contrast to the lower accuracy of the "so-called" reference agar screen test.

Anti-Bacterial Agents↗

PubMed1998

Clinical strategies for serious infection: a European perspective.

Antimicrobial resistance in nosocomial isolates is of increasing concern to the clinician, particularly in intensive care units. With more expensive drugs and prolonged periods of hospitalization required, resistance can result in increased healthcare costs. For the patient, infection with multiply resistant strains of bacteria is associated with high mortality rates. This review focuses on the prevalence of nosocomial infections throughout Europe, with particular emphasis on the prevalence of resistance to common antimicrobial agents. The beta-lactams are the most frequently prescribed antimicrobials, and the growing importance of extended spectrum beta-lactamases and the hyperproduction of chromosomal beta-lactamase by stably derepressed mutants in the development of microbial resistance are discussed. Given that the most common reason for modification of an initial empiric antibiotic treatment is the isolation of microorganisms not susceptible to the initial choice of treatment, the results from two European multicenter trials comparing the efficacy of the carbapenems, meropenem, and imipenem/cilastatin, for the treatment of serious nosocomial infections, are appraised. In light of these results, it can be concluded that the carbapenems are effective as initial empiric monotherapy for nosocomial infections because of their broad spectrum of efficacy and stability to beta-lactamases.

Bacterial Infections↗

PubMed1998

Expanding the options for risk-based therapy in febrile neutropenia.

Fever in neutropenic cancer patients is often due to the development of an infection. The standard management of febrile neutropenic patients involves the administration of empiric, hospital-based, parenteral antibiotic therapy. Although this treatment strategy has evolved from experience in high-risk patients with hematological malignancies, in whom bacterial infection can result in substantial morbidity and mortality, it has been adopted for all patients with febrile neutropenia, largely because of the inability of clinicians to reliably distinguish between patients who are at high risk for developing such morbidity/mortality and those who are not. The development of risk-assessment models has facilitated the recognition of high-, moderate-, and low-risk subgroups among febrile neutropenic patients and allows the administration of outpatient antibiotic therapy to the moderate- and low-risk groups, with the same degree of efficacy and safety as hospital-based therapy. Monotherapy with the carbapenems (imipenem/cilastatin and meropenem), with their broad spectrum of activity and established efficacy in high-risk patients, represents realistic options for risk-based treatment of febrile neutropenic patients within and outside the hospital setting.

Anti-Bacterial Agents↗

PubMed1998

Antimicrobial susceptibility patterns for pathogens isolated from patients in Latin American medical centers with a diagnosis of pneumonia: analysis of results from the SENTRY Antimicrobial Surveillance Program (1997). SENTRY Latin America Study Group.

Pneumonia is the most common fatal hospital-acquired infection, with attributable mortality rates ranging from 30 to 60%. Rapid initiation of optimal antimicrobial therapy is essential for obtaining treatment success. In this report the antimicrobial susceptibility of 556 strains from the lower respiratory tract were collected by the SENTRY Antimicrobial Surveillance Program (1997). These strains were isolated from hospitalized patients with pneumonia in 10 Latin American centers (6 countries) as part of this 68-center worldwide program. The isolates were susceptibility tested against more than 70 drugs (35 reported) by the reference broth microdilution method. Klebsiella pneumoniae and Escherichia coli phenotypically consistent with extended spectrum beta-lactamase (ESBL) production were characterized further by ribotyping and pulsed-field gel electrophoresis. The five most frequently isolated species were (n/%): Pseudomonas aeruginosa (149/26.8%), Staphylococcus aureus (127/22.8%), Acinetobacter spp. (66/11.9%), Klebsiella spp. (56/10.1%), and Enterobacter spp. (40/7.2%). P. aeruginosa demonstrated high rates of resistance to a majority of the antimicrobial drugs tested. Carbapenems, amikacin, and piperacillin/tazobactam demonstrated the highest susceptibility rates (73.8-77.2%) against P. aeruginosa, however the lowest resistance rate was observed for cefepime (6.7%). Acinetobacter spp. also showed very high rates of resistance and the most active compounds were imipenem and meropenem (89.0% susceptibility) followed by the tetracyclines. Cephalosporin susceptibilities among Klebsiella spp. were low: cefoxitin, 73.0%; ceftazidime, 69.4%; and ceftriaxone, 65.9%. Approximately 37% and 28% of K. pneumoniae and E. coli isolates, respectively, were considered ESBL producers based on NCCLS criteria. Ceftriaxone was active against only 52.5% of Enterobacter spp. isolates, whereas cefepime was active against 90.0% of isolates (MIC50, < or = 0.12 microgram/mL). Oxacillin resistance was detected in nearly 50% of S. aureus isolates. The most active drugs against S. aureus were vancomycin, teicoplanin, and quinupristin/dalfopristin (MIC90, 1 microgram/mL). In summary, our study of pneumonias in Latin American medical centers demonstrated a greatly increased prevalence of Acinetobacter spp. and higher resistance rates among Gram-negative bacilli when compared with similar controlled studies from North America.

Anti-Bacterial Agents↗

PubMed1999

Determination of the antimicrobial activity of 29 clinically important compounds tested against fastidious HACEK group organisms.

HACEK group organisms are very fastidious organisms (Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominus, Eikenella corrodens, Kingella spp.) that can produce serious invasive infections such as endocarditis. Problems with susceptibility testing methods and their rarity of isolation limit available information of therapeutic choices, particularly among newer antimicrobial agents. Forty-two HACEK strains were tested by the Etest (AB BIODISK, Solna, Sweden) method against 29 antimicrobial agents. Nearly all compounds exhibited activity with best potency observed among the tested beta-lactamase inhibitor combinations, "third- or fourth-generation" cephems, meropenem, fluoroquinolones, and rifampin. Numerous therapeutic options appear possible for initial parenteral treatment followed by oral "step-down" or switch therapy. Each case of HACEK infection therapy should be guided by accurate susceptibility tests, for which the Etest seems preferred for these fastidious species.

Anti-Bacterial Agents↗

PubMed2000

Cephalosporins, carbapenems, and monobactams.

Nonpenicillin beta-lactams exhibit a variable spectrum of antimicrobial activity, have a wide range of clinical uses and a favorable safety profile. Cefepime's twice-daily dosage and increased activity against Enterobacteriaceae may offer some advantages over older cephalosporins. The carbapenems offer a broad antimicrobial spectrum, and meropenem has an improved safety profile compared with imipenem. Aztreonam is a useful alternative for patients with aerobic gram-negative infections who are allergic to penicillin. The emergence of resistant organisms, however, is an increasing problem with the frequent use of these antibiotics.

Bacterial Infections↗

PubMed2000

In vitro activities of fourteen antimicrobial agents against obligately anaerobic bacteria.

The in vitro activities of fourteen antimicrobial agents were tested against 292 clinical isolates of obligately anaerobic bacteria using the broth microdilution technique. Taking all strains as a group the MIC(50/90) (mg/l) values were metronidazole and imipenem 0.25/1, meropenem 0.25/0.5, trovafloxacin 0.25/1, gatifloxacin and moxifloxacin 0.5/2, levofloxacin 2/16, ciprofloxacin 4/32, clindamycin 0.5/8, amoxycillin/clavulanate 1/4, doxycycline and chloramphenicol 2/4, erythromycin 4/>32 and penicillin G 16/>32.

Anti-Bacterial Agents↗

PubMed2001

Properties of multidrug-resistant, ESBL-producing Proteus mirabilis isolates and possible role of beta-lactam/beta-lactamase inhibitor combinations.

At our institution, isolation rates of clinical strains of ESBL-producing Proteus mirabilis increased to 8.8% of all P. mirabilis isolates during the period 1997-1999. To evaluate the susceptibility of ESBL-producing P. mirabilis strains against commonly used drugs, we studied 50 non-duplicated isolates selected on the basis of synergy between clavulanate and beta-lactams (ceftazidime, aztreonam, cefotaxime, and ceftriaxone). The presence of ESBL-coding genes was confirmed by colony hybridization with bla(TEM-1) and bla(SHV-1) probes. Minimum inhibitory concentrations of several antimicrobial agents for each isolate were obtained using the Etest method. All strains were encoding for TEM-derived enzymes. Gene sequencing showed that at least three different genes (TEM-15, TEM-20, and TEM-52) were present. These enzymes have not been previously reported in P. mirabilis. Isolates were characterized by: (a) reduced susceptibility or resistance to third- and fourth-generation cephalosporins (MIC > or = 2 mg/l), (b) resistance to piperacillin that was abolished by tazobactam (MIC > or = 256 vs. < or = 2 mg/l, respectively), (c) multiple antibiotic resistance that included gentamicin, fluoroquinolones and co-trimoxazole. Therapeutic failure and lack of eradication of ESBL-positive P. mirabilis by third-generation cephalosporins has been repeatedly observed both at our Institution and elsewhere. Piperacillin-tazobactam, as well as amikacin and meropenem appear to be important therapeutic options for infections due to multidrug-resistant, ESBL-producing P. mirabilis isolates.

Anti-Bacterial Agents↗

PubMed2001

Antibiotic selective pressure and development of bacterial resistance.

This study evaluates the development of resistance in Gram-negative rods to cefotaxime and ceftazidime, ofloxacin and ciprofloxacin, gentamicin and amikacin, meropenem and ampicillin/sulbactam over a five year period of use (1994-1998) at the University Hospital in Olomouc, Czech Republic. The development of bacterial resistance was linked with antibiotic use and hence selective pressure which was specific for the type of antibiotic and the bacterial species. Statistically significant correlations were found for the use of ofloxacin and resistance in Escherichia coli, Proteus vulgaris and Providencia rettgeri; cefotaxime and Enterobacter cloacae; ceftazidime and Acinetobacter spp., Enterobacter agglomerans and Proteus vulgaris; and gentamicin and Proteus mirabilis.

Aminoglycosides↗

PubMed2001

Nosocomial bloodstream infections in a Turkish university hospital: study of Gram-negative bacilli and their sensitivity patterns.

Treatment of nosocomial bacteraemia is usually governed by the surveillance results of the particular unit. Such results are especially important when antimicrobial resistance rates are high. Multiresistant isolates including Gram-negatives producing extended-spectrum beta-lactamases have been frequently reported in tertiary care units in Turkey. In this study, antimicrobial susceptibilities of Gram-negative blood isolates (n=348) were determined by microbroth dilution tests. The results showed carbapenems (meropenem and imipenem) to be uniformly more potent in vitro than any other drug against the Enterobacteriaceae. Quinolone antibiotics were more active in vitro than aminoglycosides against a range of bacteria. Gram-negative bloodstream isolates were highly resistant to many antimicrobial agents in the hospital. In order to prevent hospital infection and antimicrobial resistance, surveillance of aetiological agents must be performed regularly.

4-Quinolones↗

PubMed2001

Antimicrobial susceptibility of potentially pathogenic halophilic vibrios isolated from seafood.

Susceptibility patterns to 27 antimicrobial agents and beta-lactamase production were investigated in potentially pathogenic halophilic vibrios from seafood. The effect of salinity on the response to the drugs in vitro was also studied. All isolates were uniformly sensitive to choramphenicol, imipenem, meropenem but resistant to lincomycin. All were highly sensitive to oxolinic acid, trimethoprim-sulphamethoxazole, doxycycline, flumequine, cefotaxime, nalidixic acid and ciprofloxacin. Some strains of V. harveyi, V. alginolyticus and V. parahaemolyticus apparently had mechanisms of resistance to several beta-lactam antibiotics other than by the production of beta-lactamases. Sixty-nine strains produced penicillinase but a low correlation between beta-lactamase activity and resistance to beta-lactam antibiotics was noted. The salt concentration affected the in vitro susceptibility of halophilic vibrios and the effect of salinity depended on both the individual strains and the antimicrobial tested.

Animals↗

PubMed2002

Susceptibility patterns of Gram-negative bacteria from a Polish intensive care unit, 1997-2000.

The susceptibility of Gram-negative bacterial strains (n=400) isolated from clinical specimens of children hospitalized in a Polish intensive care unit (ICU) between 1997 and 2000 was tested. Meropenem, imipenem and ciprofloxacin were most active (>90% susceptibility) against the tested isolates, with no observed reduction in activity over 4 years. Extended-spectrum beta-lactamases and AmpC beta-lactamase producers among Enterobacteriaceae isolates from this ICU continued to be a serious therapeutic problem, although the carbapenems were highly active against these resistance phenotypes. Resistance to aminoglycosides (gentamicin, tobramycin) and ceftazidime was a characteristic of >40% of tested isolates.

Anti-Bacterial Agents↗

PubMed2002

In vitro activity of ertapenem (MK-0826) against multi-drug resistant Streptococcus pneumoniae compared with 13 other antimicrobials.

We tested ertapenem (MK-0826), a new carbapenem, and 13 other antimicrobials by microbroth dilution against 102 isolates of Streptococcus pneumoniae, selected to include organisms resistant to a variety of drug classes. Ertapenem MICs ranged from < or =0.008 to 4 mg/l, MIC(50)=0.5 mg/l, and MIC(90)=2 mg/l. Based on MIC(90), ertapenem potency was 4-fold greater than cefuroxime, 2-fold greater than amoxycillin/clavulanate, =penicillin, 2-fold less than meropenem and ceftriaxone, and 4-fold less than imipenem. Other drug classes including macrolides, tetracycline and fluoroquinolones were less potent overall than the carbapenems. Linezolid (MIC(90)=1 mg/l) was the only agent tested for which all isolates were fully susceptible. Activity of ertapenem decreased as MICs to penicillins, cephalosporins, other carbapenems and macrolides increased. Isolates resistant to clindamycin, tetracycline or fluoroquinolones showed no obvious decrease in ertapenem activity when compared with susceptible isolates with the majority of isolates resistant to these drug classes inhibited by ertapenem at concentrations less than 1 mg/l. Ertapenem may prove useful as an alternative to ceftriaxone and other agents in the treatment of community-acquired pneumonia (CAP) due to S. pneumoniae, including infections caused by organisms with reduced susceptibilities to other antimicrobial agents.

Anti-Bacterial Agents↗

PubMed2002

In vitro activity of 15 antimicrobial agents against clinical isolates of Clostridium difficile in Kuwait.

A total of 73 clinical isolates of Clostridium difficile isolated from stool/rectal swabs of patients admitted to the intensive care units at Mubarak Hospital, Ibn Sina Hospital Burn unit and Haematology wards at the Kuwait Cancer Control Centre, were investigated for their susceptibility to 15 antibiotics using the Etest. Amoxycillin-clavulanic acid, ampicillin, meropenem, metronidazole, penicillin, piperacillin, piperacillin/tazobactam, teicoplanin and vancomycin had excellent activities with MIC(90)s of 0.38, 0.5, 1, 0.19, 1.5, 2, 3, 0.25 and 0.75 mg/l, respectively. Of the 73 C. difficile isolates, 86% were resistant to imipenem (MIC(90) >32 mg/l) and almost 97% were resistant to trovafloxacin (MIC(90)>256 mg/l). Forty eight percent of the isolates were resistant to clindamycin. A total of 18 isolates were highly clindamycin-resistant with an MIC of >256 mg/l; 10 of these were toxin producers. Multiple antibiotic resistance (two or more antibiotics) was noted in 63 isolates. These were more common among the toxigenic strains than the non-toxigenic strains by a ratio of 2.5:1.

Anti-Bacterial Agents↗

PubMed2003

Sustained activity and spectrum of selected extended-spectrum beta-lactams (carbapenems and cefepime) against Enterobacter spp. and ESBL-producing Klebsiella spp.: report from the SENTRY antimicrobial surveillance program (USA, 1997-2000).

Enterobacter spp. and Klebsiella spp. are important clinical pathogens that frequently exhibit resistance to third-generation cephalosporins. In Enterobacter spp. strains, resistance is usually due to derepression of the Amp C locus, whereas plasmid-encoded extended-spectrum beta-lactamases (ESBLs) are primarily responsible for resistance in Klebsiella spp. Here we report the results from the SENTRY Antimicrobial Surveillance Program concerning the rates and trends of resistance to extended-spectrum beta-lactams and other antimicrobial agents in Enterobacter spp. and Klebsiella spp. isolated between 1997 and 2000 in participating hospitals in the United States. Among Enterobacter spp., resistance (MIC>or=32 mg/l) to aztreonam, ceftazidime and ceftriaxone ranged from 12.3 to 21.2% over the 4 years, whereas resistance in Klebsiella (MIC>or=2 mg/l) ranged from 5.9 to 6.8%. There was no trend toward increased resistance to these beta-lactam agents over the monitored period. Carbapenems (imipenem, meropenem) and cefepime had excellent activity against both ceftazidime-susceptible and -resistant Enterobacter spp. and Klebsiella spp. (>99% susceptible), although the minimum inhibitory concentration values of cefepime were higher in ceftazidime-resistant isolates compared with ceftazidime-susceptible isolates. Co-resistance to other antimicrobial agents was common in both tested genus groups.

Carbapenems↗