Association of Antibiotic Utilization Measures and Control of Multiple-Drug Resistance in<i>Klebsiella pneumoniae</i>

Patterson, Jan E.; Hardin, Thomas C.; Kelly, Cindy; Garcia, Rosa; Jorgensen, James H.

doi:10.1086/501787

Cited by 140 publications

(73 citation statements)

References 12 publications

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“…Some authors have suggested that use of ␤-lactam/␤-lactamase inhibitor combinations, rather than cephalosporins, as workhorse empirical therapy for infections suspected as being due to gram-negative bacilli, may facilitate control of ESBL producers (296,311,341). The mechanism by which these drugs may reduce infections with ESBL producers is not certain.…”

Section: Infection Control When Esbl-producing Organisms Are Already mentioning

confidence: 99%

Extended-Spectrum β-Lactamases: a Clinical Update

2005

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SUMMARY Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli. In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.

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Section: Infection Control When Esbl-producing Organisms Are Already mentioning

confidence: 99%

Extended-Spectrum β-Lactamases: a Clinical Update

2005

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“…(16,43,215,216,323,355,365). While the mechanism for decreasing ESBL-producing isolates is not clear, it must be noted that the efficacy of ␤-lactam-␤-lactamase inhibitor combinations may be reduced for organisms VOL.…”

Section: ␤-Lactamase Inhibitors In Clinical Practicementioning

confidence: 99%

Three Decades of β-Lactamase Inhibitors

Drawz¹,

2010

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SUMMARYSince the introduction of penicillin, β-lactam antibiotics have been the antimicrobial agents of choice. Unfortunately, the efficacy of these life-saving antibiotics is significantly threatened by bacterial β-lactamases. β-Lactamases are now responsible for resistance to penicillins, extended-spectrum cephalosporins, monobactams, and carbapenems. In order to overcome β-lactamase-mediated resistance, β-lactamase inhibitors (clavulanate, sulbactam, and tazobactam) were introduced into clinical practice. These inhibitors greatly enhance the efficacy of their partner β-lactams (amoxicillin, ampicillin, piperacillin, and ticarcillin) in the treatment of seriousEnterobacteriaceaeand penicillin-resistant staphylococcal infections. However, selective pressure from excess antibiotic use accelerated the emergence of resistance to β-lactam-β-lactamase inhibitor combinations. Furthermore, the prevalence of clinically relevant β-lactamases from other classes that are resistant to inhibition is rapidly increasing. There is an urgent need for effective inhibitors that can restore the activity of β-lactams. Here, we review the catalytic mechanisms of each β-lactamase class. We then discuss approaches for circumventing β-lactamase-mediated resistance, including properties and characteristics of mechanism-based inactivators. We next highlight the mechanisms of action and salient clinical and microbiological features of β-lactamase inhibitors. We also emphasize their therapeutic applications. We close by focusing on novel compounds and the chemical features of these agents that may contribute to a “second generation” of inhibitors. The goal for the next 3 decades will be to design inhibitors that will be effective for more than a single class of β-lactamases.

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“…The use of certain classes of antimicrobials, such as 3rd-generation cephalosporins is implicated in the development of resistance caused by enzymes in the group of ESBLs [4][5][6] . Restriction of such drugs causes a reduction in the incidence of these beta-lactamases in hospitals [4,6] .…”

Section: Introductionmentioning

confidence: 99%

The Effect of a 4th Generation-Cephalosporin Introduction upon the Incidence of Multidrug-Resistant Gram-Negative Bacteria in a Non-Teaching Hospital

Furtado¹,

Perdiz²,

Medeiros³

2008

American J. of Infectious Diseases

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Problem statement: Antimicrobial resistance is a worrisome situation in hospitals around the world and the misuse of certain classes of antimicrobials has contributed for this situation. Approach: We performed a prospective surveillance study on the incidence of multi-drug resistant bacteria before (phase 1) and after (phase 2) the introduction of a 4th-generation cephalosporin in a non-teaching hospital. Results: There was a significant reduction in the incidence of Enterobacter species (from 1.3 isolates per 100 patient-days to 0.39 isolates per 100 patient-days, p = 0.01) between the two periods. We also observed a reduction in the consumption of ceftazidime (from 64.3 DDD per 1000 patient-days to 29.6 DDD per 1000 patient-days, p = 0.002) and ceftriaxone (from 323.9 DDD per 1000 patient-days to 246.2 DDD per 1000 patient-days, p = 0.01). Conclusion: The introduction of a 4th-generation cephalosporin in our setting resulted in an important reduction in the incidence of Enterobacter species.

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Association of Antibiotic Utilization Measures and Control of Multiple-Drug Resistance inKlebsiella pneumoniae

Abstract: Antibiotic-use measures may be particularly important for control of MDR K. pneumoniae, whether emergence is clonal or polyclonal.

Cited by 140 publications

References 12 publications

Extended-Spectrum β-Lactamases: a Clinical Update

Extended-Spectrum β-Lactamases: a Clinical Update

Three Decades of β-Lactamase Inhibitors

The Effect of a 4th Generation-Cephalosporin Introduction upon the Incidence of Multidrug-Resistant Gram-Negative Bacteria in a Non-Teaching Hospital

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