A Cross-Canada Surveillance of Antimicrobial Resistance in Respiratory Tract Pathogens

OBJECTIVE: To determine the prevalence of antimicrobial resistance in clinical isolates ofStreptococcus pneumoniae, Haemophilus influenzaeandMoraxella catarrhalisfrom medical centres across Canada.METHODS: Fifty laboratories from across Canada were asked to collect up to 25 consecutive clinical isolates ofS pneumoniae,H influenzaeandM catarrhalisat some time between September 1994 and May 1995, and then again between September and December of 1996. A total of 2364S pneumoniae, 575H influenzaeand 200M catarrhalissamples were collected.H influenzaeandM catarrhalisisolates were tested for the production of beta-lactamase.S pneumoniaeisolates were characterized as penicillin susceptible, intermediately resistant or high level penicillin-resistant. Minimal inhibitory concentrations (MICs) were determined using a microbroth dilution technique described by the National Committee of Clinical Laboratory Standards.RESULTS: Between the two collection periods, there was a significant increase in highly penicillin-resistantS pneumoniaefrom 2.1% to 4.4% (P<0.05) and an increase in intermediately penicillin-resistant strains from 6.4% to 8.9% (P<0.05). A significant increase in high level penicillin-resistantS pneumoniaewas noted among paediatric isolates. No significant difference in the susceptibilities of comparator agents was detected. A significant increase in the number of beta-lactamase producingH influenzae, 34% to 43% (P<0.05) was observed. Ninety-five per cent ofM catarrhalisisolates were beta-lactamase producers in both time periods.CONCLUSIONS: During the course of this study, the incidence of penicillin resistance inS pneumoniaedoubled. As a result of this increase, infections due to this organism in sites where poor penetration of beta-lactam antibiotics occur may become increasingly difficult to manage.

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Piperacillin/Tazobactam: A New Beta-Lactam/Beta-Lactamase Inhibitor Combination

Annals of Pharmacotherapy ◽

10.1177/106002809502900510 ◽

1995 ◽

Vol 29 (5) ◽

pp. 501-514 ◽

Cited By ~ 24

Author(s):

Lori L Schoonover ◽

Donna J Occhipinti ◽

Keith A Rodvold ◽

Larry H Danziger

Keyword(s):

Antimicrobial Activity ◽

Clinical Efficacy ◽

Clinical Laboratory ◽

National Committee ◽

Beta Lactamase ◽

Beta Lactam ◽

In Vitro Susceptibility ◽

Tract Infections ◽

Inhibitor Combination ◽

Lactamase Inhibitor

Objective: To discuss the antimicrobial activity, pharmacokinetics, clinical efficacy, and adverse effect profile of piperacillin/tazobactam, a new beta-lactam/beta-lactamase inhibitor combination. Data Sources: Literature was identified by MEDLINE search of the medical literature, review of selected references, and data provided by the manufacturer. Study Selection: In vitro susceptibility data were surveyed from studies following the methods of the National Committee for Clinical Laboratory Standards. Data evaluating clinical efficacy were selected from all published trials and abstracts. Additional information concerning safety, chemistry, and pharmacokinetics was reviewed. Data Synthesis: The antimicrobial activity of piperacillin is enhanced by addition of tazobactam against gram-positive, gram-negative, and anaerobic bacteria. Tazobactam is active against a broad spectrum of plasmid and chromosomally mediated enzymes and has minimal ability to induce class I chromosomally mediated beta-lactamase enzymes. Piperacillin/tazobactam's expanded activity appears encouraging in the treatment of mixed aerobic and anaerobic infections. Direct comparisons of ticarcillin/clavulanate and piperacillin/tazobactam for the treatment of lower respiratory tract infections showed piperacillin/tazobactam to be clinically superior, and in the treatment of skin and soft tissue infections the 2 agents were comparable. For the treatment of intraabdominal infections, piperacillin/tazobactam was at least as effective as imipenem/cilastatin and clindamycin plus gentamicin. Conclusions: The combination of tazobactam with piperacillin results in an antimicrobial agent with enhanced activity against most beta-lactamase–producing organisms. Preliminary data indicate that piperacillin/tazobactam has proven clinical efficacy in the treatment of a variety of infections, especially polymicrobic infections.

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A TEM-derived extended-spectrum beta-lactamase in Pseudomonas aeruginosa.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.11.2488 ◽

1996 ◽

Vol 40 (11) ◽

pp. 2488-2493 ◽

Cited By ~ 47

Author(s):

P Mugnier ◽

P Dubrous ◽

I Casin ◽

G Arlet ◽

E Collatz

Keyword(s):

Pseudomonas Aeruginosa ◽

Clinical Strain ◽

Beta Lactamase ◽

Beta Lactam ◽

Aminoglycoside Resistance ◽

Double Mutation ◽

Extended Spectrum Beta Lactamase ◽

Beta Lactam Antibiotics ◽

Extended Spectrum ◽

High Level

A clinical strain of Pseudomonas aeruginosa, PAe1100, was found to be resistant to all antipseudomonal beta-lactam antibiotics and to aminoglycosides, including gentamicin, amikacin, and isepamicin. PAe1100 produced two beta-lactamases, TEM-2 (pI 5.6) and a novel, TEM-derived extended-spectrum beta-lactamase called TEM-42 (pI 5.8), susceptible to inhibition by clavulanate, sulbactam, and tazobactam. Both enzymes, as well as the aminoglycoside resistance which resulted from AAC(3)-IIa and AAC(6')-I production, were encoded by an 18-kb nonconjugative plasmid, pLRM1, that could be transferred to Escherichia coli by transformation. The gene coding for TEM-42 had four mutations that led to as many amino acid substitutions with respect to TEM-2: Val for Ala at position 42 (Ala42), Ser for Gly238, Lys for Glu240, and Met for Thr265 (Ambler numbering). The double mutation Ser for Gly238 and Lys for Glu240, which has so far only been described in SHV-type but not TEM-type enzymes, conferred concomitant high-level resistance to cefotaxime and ceftazidime. The novel, TEM-derived extended-spectrum beta-lactamase appears to be the first of its class to be described in P. aeruginosa.

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Stigmasterol: An adjuvant for beta lactam antibiotics against beta-lactamase positive clinical isolates

Steroids ◽

10.1016/j.steroids.2017.10.016 ◽

2017 ◽

Vol 128 ◽

pp. 68-71 ◽

Cited By ~ 6

Author(s):

Tong Woei Yenn ◽

Muhammad Arslan Khan ◽

Nur Amiera Syuhada ◽

Leong Chean Ring ◽

Darah Ibrahim ◽

...

Keyword(s):

Clinical Isolates ◽

Beta Lactamase ◽

Beta Lactam ◽

Beta Lactam Antibiotics

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Characterization of Multidrug Resistant Extended-Spectrum Beta-Lactamase-ProducingEscherichia coliamong Uropathogens of Pediatrics in North of Iran

BioMed Research International ◽

10.1155/2015/309478 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 24

Author(s):

Mohammad Sadegh Rezai ◽

Ebrahim Salehifar ◽

Alireza Rafiei ◽

Taimour Langaee ◽

Mohammadreza Rafati ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Multidrug Resistant ◽

Beta Lactamase ◽

Beta Lactam ◽

Extended Spectrum Beta Lactamase ◽

E Coli ◽

Beta Lactam Antibiotics ◽

Extended Spectrum ◽

Extended Spectrum Beta Lactamases ◽

North Of Iran

Escherichia coliremains as one of the most important bacteria causing infections in pediatrics and producing extended-spectrum beta-lactamases (ESBLs) making them resistant to beta-lactam antibiotics. In this study we aimed to genotype ESBL-producingE. coliisolates from pediatric patients for ESBL genes and determine their association with antimicrobial resistance. One hundred of theE. coliisolates were initially considered ESBL producing based on their MIC results. These isolates were then tested by polymerase chain reaction (PCR) for the presence or absence ofCTX,TEM,SHV,GES, andVEBbeta-lactamase genes. About 30.5% of isolatedE. coliwas ESBL-producing strain. TheTEMgene was the most prevalent (49%) followed bySHV(44%),CTX(28%),VEB(8%), andGES(0%) genes. The ESBL-producingE. coliisolates were susceptible to carbapenems (66%) and amikacin (58%) and showed high resistance to cefixime (99%), colistin (82%), and ciprofloxacin (76%). In conclusion, carbapenems were the most effective antibiotics against ESBl-producingE. coliin urinary tract infection in North of Iran. The most prevalent gene is the TEM-type, but the other resistant genes and their antimicrobial resistance are on the rise.

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Sensitivity to beta-lactam antibiotics and production of beta-lactamase of gram-negative clinical isolates

Antonie van Leeuwenhoek ◽

10.1007/bf00404587 ◽

1985 ◽

Vol 51 (5-6) ◽

pp. 600-602

Author(s):

J. L. Hoekstra ◽

A. W. Houben ◽

E. E. Stobberingh ◽

C. P. A. van Boven

Keyword(s):

Clinical Isolates ◽

Beta Lactamase ◽

Beta Lactam ◽

Gram Negative ◽

Beta Lactam Antibiotics

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Antimicrobial Resistance among Clinical Isolates ofStreptococcus pneumoniae in the United States during 1999–2000, Including a Comparison of Resistance Rates since 1994–1995

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.6.1721-1729.2001 ◽

2001 ◽

Vol 45 (6) ◽

pp. 1721-1729 ◽

Cited By ~ 390

Author(s):

Gary V. Doern ◽

Kristopher P. Heilmann ◽

Holly K. Huynh ◽

Paul R. Rhomberg ◽

Stacy L. Coffman ◽

...

Keyword(s):

United States ◽

Antimicrobial Resistance ◽

Antimicrobial Agents ◽

Rank Order ◽

The United States ◽

Clinical Isolates ◽

Beta Lactam ◽

High Level ◽

Resistance Rates

ABSTRACT A total of 1,531 recent clinical isolates of Streptococcus pneumoniae were collected from 33 medical centers nationwide during the winter of 1999–2000 and characterized at a central laboratory. Of these isolates, 34.2% were penicillin nonsusceptible (MIC ≥ 0.12 μg/ml) and 21.5% were high-level resistant (MIC ≥ 2 μg/ml). MICs to all beta-lactam antimicrobials increased as penicillin MICs increased. Resistance rates among non-beta-lactam agents were the following: macrolides, 25.2 to 25.7%; clindamycin, 8.9%; tetracycline, 16.3%; chloramphenicol, 8.3%; and trimethoprim-sulfamethoxazole (TMP-SMX), 30.3%. Resistance to non-beta-lactam agents was higher among penicillin-resistant strains than penicillin-susceptible strains; 22.4% of S. pneumoniae were multiresistant. Resistance to vancomycin and quinupristin-dalfopristin was not detected. Resistance to rifampin was 0.1%. Testing of seven fluoroquinolones resulted in the following rank order of in vitro activity: gemifloxacin > sitafloxacin > moxifloxacin > gatifloxacin > levofloxacin = ciprofloxacin > ofloxacin. For 1.4% of strains, ciprofloxacin MICs were ≥4 μg/ml. The MIC90s (MICs at which 90% of isolates were inhibited) of two ketolides were 0.06 μg/ml (ABT773) and 0.12 μg/ml (telithromycin). The MIC90 of linezolid was 2 μg/ml. Overall, antimicrobial resistance was highest among middle ear fluid and sinus isolates of S. pneumoniae; lowest resistance rates were noted with isolates from cerebrospinal fluid and blood. Resistant isolates were most often recovered from children 0 to 5 years of age and from patients in the southeastern United States. This study represents a continuation of two previous national studies, one in 1994–1995 and the other in 1997–1998. Resistance rates with S. pneumoniae have increased markedly in the United States during the past 5 years. Increases in resistance from 1994–1995 to 1999–2000 for selected antimicrobial agents were as follows: penicillin, 10.6%; erythromycin, 16.1%; tetracycline, 9.0%; TMP-SMX, 9.1%; and chloramphenicol, 4.0%, the increase in multiresistance was 13.3%. Despite awareness and prevention efforts, antimicrobial resistance with S. pneumoniae continues to increase in the United States.

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Beta-Lactamase Inhibitors: Another Approach to Overcoming Antimicrobial Resistance

Infection Control ◽

10.1017/s0195941700066972 ◽

1987 ◽

Vol 8 (1) ◽

pp. 36-40 ◽

Cited By ~ 13

Author(s):

Richard H. Parker ◽

Mark Eggleston

Keyword(s):

Antimicrobial Resistance ◽

Antimicrobial Agents ◽

Clinical Isolates ◽

Beta Lactamase ◽

Total Resistance ◽

Beta Lactam ◽

Beta Lactamases ◽

The Past ◽

Common Group ◽

Clinical Pathogens

Resistance of most clinical pathogens to beta-lactam antimicrobial agents is currently primarily mediated by the microorganisms' ability to product beta-lactamases. There are a variety of beta-lactamases which are primarily differentiated by whether they are plasmid- or chromosome-mediated and by their substrate and inhibition profiles. The most common group of beta-lactamases produced by clinical isolates are the plasmid-mediated TEM enzymes (Richmond-Sykes type III a) which exist in many Enterobacteriaceae, Hemophilus influenzae, and Neisseria species. Development of new beta-lactam antimicrobial agents during the past decades has resulted in a number of drugs with increased, albeit not total, resistance to beta-lactamases. Another approach has been the development of beta-lactamase inhibitors that can be used with a beta-lactam drug to overcome the resistance created by the beta-lactamase.

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Antibiotic resistance among clinical isolates of Haemophilus influenzae in the United States in 1994 and 1995 and detection of beta-lactamase-positive strains resistant to amoxicillin-clavulanate: results of a national multicenter surveillance study.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.2.292 ◽

1997 ◽

Vol 41 (2) ◽

pp. 292-297 ◽

Cited By ~ 200

Author(s):

G V Doern ◽

A B Brueggemann ◽

G Pierce ◽

H P Holley ◽

A Rauch

Keyword(s):

Haemophilus Influenzae ◽

Antimicrobial Agents ◽

Clinical Laboratory ◽

Rank Order ◽

Medical Center ◽

The United States ◽

Clinical Isolates ◽

National Committee ◽

Beta Lactamase ◽

Amoxicillin Clavulanate

A total of 1,537 clinical isolates of Haemophilus influenzae were recovered in 30 U.S. medical center laboratories between 1 November 1994 and 30 April 1995 and were characterized in a central laboratory with respect to serotype and beta-lactamase production and the in vitro activities of 15 oral antimicrobial agents. Overall, 36.4% of the isolates were found to produce beta-lactamase. The rank order of activity of six cephalosporins on the basis of MICs was cefixime > cefpodoxime > cefuroxime > loracarbef > or = cefaclor > cefprozil. On the basis of current National Committee for Clinical Laboratory Standards (NCCLS) breakpoints ages of isolates found to be resistant or intermediate to these agents were as follows: 0.1, 0.3, 6.4, 16.3, 18.3, and 29.8, respectively (National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 4th ed. M7-A4, 1995). Azithromycin was, on a weight basis, the most potent of the macrolides tested in this study, followed by erythromycin and then clarithromycin. Azithromycin was typically fourfold more active than erythromycin, which was, in turn, slightly more active than clarithromycin. However, when compared on the basis of the frequency of resistance determined by using current NCCLS breakpoints, there was essentially no difference between azithromycin and clarithromycin, i.e., 0.5 and 1.9%, respectively (P = 0.086). Interpretive breakpoints for erythromycin MIC tests versus H. influenzae have not been developed. Resistance to other non- beta-lactam agents was variable, as follows: trimethoprim-sulfamethoxazole, 9.0%; chloramphenicol, 0.2%; tetracycline, 1.3%; and rifampin, 0.3%. Two conspicuous findings in this study were the identification of 39 strains H. influenzae that were beta-lactamase negative but ampicillin intermediate or resistant (BLNAR) and, even more surprisingly, 17 beta-lactamase-positive isolates that were resistant to amoxicillin-clavulanate (BLPACR). Strains of H. influenzae in the first group have heretofore been very uncommon; organisms in the second group have not previously been described in the literature. The percentages of all study isolates comprised of BLNAR and BLPACR organisms were 2.5 and 1.1, respectively. Overall resistance to ampicillin was thus 38.9%, and that to amoxicillin-clavulanate was 4.5%.

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Penicillin-binding proteins 2b and 2x of Streptococcus pneumoniae are primary resistance determinants for different classes of beta-lactam antibiotics.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.4.829 ◽

1996 ◽

Vol 40 (4) ◽

pp. 829-834 ◽

Cited By ~ 169

Author(s):

T Grebe ◽

R Hakenbeck

Keyword(s):

Streptococcus Pneumoniae ◽

Clinical Isolate ◽

Binding Proteins ◽

Point Mutations ◽

Clinical Isolates ◽

Single Amino Acid ◽

Beta Lactam ◽

Penicillin Binding Proteins ◽

Beta Lactam Antibiotics ◽

High Level

High-level resistance to beta-lactam antibiotics in Streptococcus pneumoniae is mediated by successive alterations in essential penicillin-binding proteins (PBPs). In the present work, single amino acid changes in S. pneumoniae PBP 2x and PBP 2b that result in reduced affinity for the antibiotic and that confer first-level beta-lactam resistance are defined. Point mutations in the PBP genes were generated by PCR-derived mutagenesis. Those conferring maximal resistance to either cefotaxime (pbp2x) or piperacillin (pbp2b) were obtained after transformation of the susceptible laboratory strain R6 with the PCR-amplified PBP genes and selection on agar with various concentrations of the antibiotic. In the case of PBP 2x, transformants for which the cefotaxime MIC was 0.16 microgram/ml contained the substitution of a Thr for an Ala at position 550 (Thr550-->Ala), close to the PBP homology box Lys547SerGly, a mutation frequently observed in laboratory mutants and in a high-level cefotaxime-resistant clinical isolate as well. After further selection, transformants resisting 0.3 microgram of cefotaxime per ml were obtained; they contained the substitution Gly550 as the result of two mutations in the same codon. In PBP 2b, Thr446-->Ala, adjacent to another homology box Ser443SerAsn, was the mutation selected with piperacillin. This substitution has been described in all clinical isolates with a low-affinity PBP 2b but was distinct from point mutations found in laboratory mutants. Both pbp2b with the single mutation and a mosaic pbp2b of a clinical isolate conferred a twofold increase in piperacillin resistance. Attempts to select PBP 2b variants at higher piperacillin concentrations were unsuccessful. The mutated PBP 2b also markedly reduced the lytic response to piperacillin, suggesting that such a mutation is an important step in resistance development in clinical isolates.

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