Ceftazidime and Aztreonam Resistance inProvidencia stuartii: Characterization of a Natural TEM-Derived ExtendedSpectrum β-Lactamase, TEM-60

ABSTRACT A plasmid-encoded β-lactamase produced from a clinical strain ofProvidencia stuartii has been purified and characterized. The gene coding for the β-lactamase was cloned and sequenced. It appears to be a new natural TEM-derived enzyme, named TEM-60. Point mutations (Q39K, L51P, E104K, and R164S) are present with respect to the TEM-1 enzyme; the mutation L51P has never been previously reported, with the exception of the chromosomally encoded extended-spectrum β-lactamase PER-1. Kinetic parameters relative to penicillins, cephalosporins, and monobactams other than mechanism-based inactivators were related to the in vitro susceptibility phenotype.

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Characterization of Spontaneous, In Vitro-Selected, Rifampin-Resistant Mutants of Mycobacterium tuberculosisStrain H37Rv

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.44.12.3298-3301.2000 ◽

2000 ◽

Vol 44 (12) ◽

pp. 3298-3301 ◽

Cited By ~ 47

Author(s):

Glenn P. Morlock ◽

Bonnie B. Plikaytis ◽

Jack T. Crawford

Keyword(s):

Point Mutations ◽

Laboratory Strain ◽

Resistant Mutant ◽

Small Region ◽

Clinical Isolates ◽

Gene Coding ◽

Resistant Mutants ◽

Strain H37rv

ABSTRACT Resistance to rifampin in Mycobacterium tuberculosisresults from mutations in the gene coding for the beta subunit of RNA polymerase (rpoB). At least 95% of rifampin-resistant isolates have mutations in rpoB, and the mutations are clustered in a small region. About 40 distinct point mutations and in-frame insertions and deletions in rpoB have been identified, but point mutations in two codons, those coding for Ser531 and His526, are seen in about 70% of rifampin-resistant clinical isolates, with Ser531-to-Leu (TCG-to-TGG) mutations being by far the most common. To explore this phenomenon, we isolated independent, spontaneous, rifampin-resistant mutant versions of well-characterized M. tuberculosislaboratory strain H37Rv by plating 100 separate cultures, derived from a single low-density inoculum, onto rifampin-containing medium. Rifampin-resistant mutants were obtained from 64 of these cultures. Although we anticipated that the various point mutations would occur with approximately equal frequencies, sequencing the rpoBgene from one colony per plate revealed that 39 (60.9%) were Ser531 to Leu. We conclude that, for unknown reasons, the associated rpoB mutation occurs at a substantially higher rate than other rpoB mutations. This higher mutation rate may contribute to the high percentage of this mutation seen in clinical isolates.

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Novel OXA-10-Derived Extended-Spectrum β-Lactamases Selected In Vivo or In Vitro

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.12.3113 ◽

1998 ◽

Vol 42 (12) ◽

pp. 3113-3116 ◽

Cited By ~ 49

Author(s):

P. Mugnier ◽

I. Casin ◽

A. T. Bouthors ◽

E. Collatz

Keyword(s):

Amino Acids ◽

Pseudomonas Aeruginosa ◽

Amino Acid ◽

Clavulanic Acid ◽

Extended Spectrum ◽

Gene Coding ◽

Lactamase Gene

ABSTRACT A clinical isolate of Pseudomonas aeruginosa, PAe191, was found to be highly resistant to all anti-Pseudomonasβ-lactam antibiotics (except imipenem) and resistant also to aminoglycosides. It produced a β-lactamase (with an apparent pI of 7.6) which was not inhibited by clavulanic acid. Cloning and characterization of the β-lactamase gene showed that it coded for a novel extended-spectrum OXA-10 variant, called OXA-19, which differed from OXA-10 by nine amino acids and from OXA-13 by two, i.e., Asn in position 73 (Asn73) instead of Ser and Asp157 instead of Gly. Asparagine in position 157 is implicated in resistance to ceftazidime, while the amino acid in position 73, in this variant, seems to condition the level of resistance to penicillins. The oxa19gene was found to be inserted, in a typical integron structure, immediately downstream from anaac(6′)-Ib gene coding for an aminoglycoside acetyltransferase variant, which was called AAC(6′)-Ib9.

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Characterization of a Novel Extended-Spectrum TEM-Type β-Lactamase, TEM-164, in a Clinical Strain ofKlebsiella pneumoniaein Tunisia

Microbial Drug Resistance ◽

10.1089/mdr.2009.0900 ◽

2009 ◽

Vol 15 (3) ◽

pp. 195-199 ◽

Cited By ~ 4

Author(s):

Nahed Ben Achour ◽

Paola Sandra Mercuri ◽

Mohamed Ben Moussa ◽

Moreno Galleni ◽

Omrane Belhadj

Keyword(s):

Clinical Strain ◽

Extended Spectrum

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In vitro susceptibility of ceftolozane/tazobactam against typhoidal, non-typhoidal and extended spectrum β-lactamase-producing Salmonella

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01224-21 ◽

2021 ◽

Author(s):

Jade L. L. Teng ◽

Elaine Chan ◽

Asher C. H. Dai ◽

Gillian Ng ◽

Tsz Tuen Li ◽

...

Keyword(s):

United States ◽

Antimicrobial Agents ◽

The United States ◽

Drug Resistant ◽

Broth Microdilution ◽

In Vitro Susceptibility ◽

Extended Spectrum ◽

Control And Prevention ◽

Esbl Producers

Both typhoidal and non-typhoidal salmonellae are included in the top 15 drug-resistant threats described by the Center for Disease Control and Prevention of the United States. There is an urgent need to look for alternative antibiotics for the treatment of Salmonella infections. We examined the in vitro susceptibilities of ceftolozane/tazobactam and six other antibiotics on typhoidal and non-typhoidal salmonellae, including isolates that are extended-spectrum β-lactamase (ESBL)-positive, using the broth microdilution test. Of the 313 (52 typhoidal and 261 non-typhoidal) Salmonella isolates tested, 98.7% were susceptible to ceftolozane/tazobactam. Based on the overall MIC 50/90 values, Salmonella isolates were more susceptible to ceftolozane/tazobactam (0.25/0.5 mg/L) compared to all other comparator agents: ampicillin (≥64/≥64 mg/L), levofloxacin (0.25/1 mg/L), azithromycin (4/16 mg/L), ceftriaxone (≤0.25/4 mg/L), chloramphenicol (8/≥64 mg/L) and trimethoprim/sulfamethoxazole (1/≥8 mg/L). When comparing the activity of the antimicrobial agents against non-typhoidal Salmonella isolates according to their serogroup, ceftolozane/tazobactam had the highest activity (100%) against Salmonella serogroups D, G, I and Q isolates, whereas the lowest activity (85.7%) was observed against serogroup E isolates. All the 10 ESBL-producing Salmonella (all non-typhoidal) isolates, of which 8 were CTX-M-55-producers and 2 were CTX-M-65-producers, were sensitive to ceftolozane/tazobactam albeit with a higher MIC 50/90 value (1/2 mg/L) than non-ESBL-producers (0.25/0.5 mg/L). In summary, our data indicate that ceftolozane/tazobactam is active against most strains of both typhoidal and non-typhoidal salmonellae and also active against ESBL-producing salmonellae.

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In Vitro and In Vivo Activities of Amikacin, Cefepime, Amikacin plus Cefepime, and Imipenem against an SHV-5 Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae Strain

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.4.1287-1291.2001 ◽

2001 ◽

Vol 45 (4) ◽

pp. 1287-1291 ◽

Cited By ~ 18

Author(s):

Dóra Szabó ◽

András Máthé ◽

Zsolt Filetóth ◽

Piroska Anderlik ◽

László Rókusz ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Susceptibility Test ◽

In Vitro Susceptibility ◽

High Inoculum ◽

Extended Spectrum ◽

Inoculum Effect ◽

Do So

ABSTRACT The in vitro and in vivo effectiveness of amikacin, cefepime, and imipenem was studied using a high inoculum of an extended-spectrum β-lactamase-producing Klebsiella pneumoniae strain. An in vitro susceptibility test at the standard inoculum predicted the in vivo outcome of amikacin or imipenem while it did not do so for cefepime due to the inoculum effect.

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Biochemical Characterization of Laboratory Mutants of Extended-Spectrum β-Lactamase TEM-60

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.9.3579-3582.2004 ◽

2004 ◽

Vol 48 (9) ◽

pp. 3579-3582 ◽

Cited By ~ 6

Author(s):

Bibiana Caporale ◽

Nicola Franceschini ◽

Mariagrazia Perilli ◽

Bernardetta Segatore ◽

Gian Maria Rossolini ◽

...

Keyword(s):

Enzyme Activity ◽

Kinetic Parameters ◽

Biochemical Characterization ◽

Site Directed Mutagenesis ◽

Directed Mutagenesis ◽

Extended Spectrum

ABSTRACT Three mutants of the extended-spectrum β-lactamase TEM-60, the P51L, K104E, and S164R mutants, were constructed by site-directed mutagenesis. The kinetic parameters of the mutated enzymes and interactions of inhibitors were significantly different from those of TEM-60, revealing that the L51P mutation plays an important role in enzyme activity and stability in the TEM-60 background.

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Diagnosis and Treatment of Extended-Spectrum and AmpC β-Lactamase–Producing Organisms

Annals of Pharmacotherapy ◽

10.1345/aph.1k213 ◽

2007 ◽

Vol 41 (9) ◽

pp. 1427-1435 ◽

Cited By ~ 34

Author(s):

Katherine Yang ◽

B Joseph Guglielmo

Keyword(s):

Antibiotic Treatment ◽

English Language ◽

Randomized Clinical Trials ◽

Case Reports ◽

Treatment Options ◽

False Negative ◽

In Vitro Susceptibility ◽

Laboratory Techniques ◽

Extended Spectrum

Objective: To review the laboratory diagnosis of extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase–producing bacteria and evaluate potential treatment options. Data Sources: A PubMed search, restricted to English-language articles, was conducted (1966–May 2007) using the search terms ESBL, AmpC, diagnosis, detection, carbapenem, ertapenem, fluoroquinolone, cephalosporin, cefepime, tigecycline, and colistin. Additional references were identified through review of bibliographies of identified articles. Study Selection and Data Extraction: All studies that evaluated laboratory methods for the detection of ESBLs and AmpC β-lactamases and/or the treatment of these organisms were reviewed. All articles that were deemed to be clinically pertinent were included and critically evaluated. Data Synthesis: Numerous laboratory techniques are available for the detection of ESBLs. In contrast, laboratory techniques for detection of AmpC β-lactamases are limited, particularly for plasmid-mediated AmpC β-lactamases. Routine microbiologic testing may not detect ESBLs or AmpC β-lactamases. Optimal antibiotic treatment options are derived from limited observational studies and case reports. Randomized clinical trials evaluating appropriate antibiotic treatment options are lacking. In vitro susceptibility does not always correlate with clinical outcomes. The use of imipenem was associated with the lowest incidence of mortality in patients with bacteremia due to ESBL-producing organisms. Conclusions: Laboratory detection of ESBLs for most organisms is possible with Clinical and Laboratory Standards Institute–recommended testing. However, these tests can be associated with both false negative and false positive results, particularly with organisms that harbor both ESBL- and plasmid-mediated AmpC β-lactamases. No established guidelines exist for the detection of AmpC β-lactamases. Imipenem and meropenem are superior to other antibiotics for the treatment of serious infections due to ESBL and AmpC β-lactamase–producing gram-negative bacteria. While in vitro data demonstrate that tigecycline, ertapenem, and colistin might be potential choices, clinical experience is lacking.

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