Archive for October 24, 2015

Efficacy of doripenem and ertapenem against KPC-2-producing and non-KPC-producing Klebsiella pneumoniae with similar MICs.

J Antimicrob Chemother. 2013 Jul;68(7):1616-8.

Hagihara M1, Crandon JL, Urban C, Nicolau DP.

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1Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.



In the clinical setting, the choice of definitive drug therapy is typically guided by the antimicrobial susceptibility profile of the infecting organism. We evaluated the activity of doripenem and ertapenem against Klebsiella pneumoniae isolates with similar MICs that exhibited KPC-based and non-KPC-based genotypes.


Five doripenem-non-susceptible K. pneumoniae isolates, three producing KPC carbapenemases and two exhibiting porin modifications plus AmpC β-lactamase production, were tested in a neutropenic murine thigh infection model. The ertapenem MIC for all isolates was >32 mg/L. Regimens of 2 g of doripenem every 8 h (4 h infusion) and 1 g of ertapenem every 24 h (0.5 h infusion) simulating human concentration-time profiles were administered 2 h after inoculation. The change in bacterial density was evaluated after 24 h of therapy.


Consistent with the observed MICs, treatment with ertapenem resulted in minimal activity against all isolates tested. When comparing the activity of doripenem between the KPC and non-KPC producers with doripenem MICs of 8 mg/L, significantly better activity was noted for the non-KPC producer (P<0.001). Likewise, when comparing the two KPC-producing isolates with doripenem MICs of 24 mg/L and >32 mg/L with the non-KPC producer with an MIC of 32 mg/L, significantly greater activity was noted for the non-KPC producer (P<0.001).


When doripenem MICs were similar, activity was greater for non-KPC-producing isolates when compared with KPC producers. While the in vitro MIC is typically the sole method utilized to aid in drug selection, these data suggest that the genetic driver behind these MICs may also play a role in predicting in vivo activity.



October 24, 2015 at 7:33 pm

Mechanisms of antimicrobial resistance in Gram-negative bacilli.

Ann Intensive Care. 2015 ;5(1):61.


Ruppé É1, Woerther PL, Barbier F.

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1Department of Infectious Diseases, Genomic Research Laboratory, Geneva University Hospitals, Geneva, Switzerland,


The burden of multidrug resistance in Gram-negative bacilli (GNB) now represents a daily issue for the management of antimicrobial therapy in intensive care unit (ICU) patients.

In Enterobacteriaceae, the dramatic increase in the rates of resistance to third-generation cephalosporins mainly results from the spread of plasmid-borne extended-spectrum beta-lactamase (ESBL), especially those belonging to the CTX-M family.

The efficacy of beta-lactam/beta-lactamase inhibitor associations for severe infections due to ESBL-producing Enterobacteriaceae has not been adequately evaluated in critically ill patients, and carbapenems still stands as the first-line choice in this situation.

However, carbapenemase-producing strains have emerged worldwide over the past decade. VIM- and NDM-type metallo-beta-lactamases, OXA-48 and KPC appear as the most successful enzymes and may threaten the efficacy of carbapenems in the near future.

ESBL- and carbapenemase-encoding plasmids frequently bear resistance determinants for other antimicrobial classes, including aminoglycosides (aminoglycoside-modifying enzymes or 16S rRNA methylases) and fluoroquinolones (Qnr, AAC(6′)-Ib-cr or efflux pumps), a key feature that fosters the spread of multidrug resistance in Enterobacteriaceae.

In non-fermenting GNB such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia, multidrug resistance may emerge following the sole occurrence of sequential chromosomal mutations, which may lead to the overproduction of intrinsic beta-lactamases, hyper-expression of efflux pumps, target modifications and permeability alterations.

P. aeruginosa and A. baumannii also have the ability to acquire mobile genetic elements encoding resistance determinants, including carbapenemases.

Available options for the treatment of ICU-acquired infections due to carbapenem-resistant GNB are currently scarce, and recent reports emphasizing the spread of colistin resistance in environments with high volume of polymyxins use elicit major concern.



October 24, 2015 at 7:32 pm

Successful containment and infection control of a Carbapenem-resistant Klebsiella pneumoniae outbreak in an Italian hospital.

New Microbiol. 2014 Jan;37(1):87-90.

Gaibani P1, Colombo R, Arghittu M, Cariani L, Ambretti S, Bua G, Lombardo D, Landini MP, Torresani E, Sambri V.

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1Operative Unit of Clinical Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St.Orsola-Malpighi University Hospital, Bologna, Italy.


We describe an outbreak of a carbapenemase-producing Klebsiella pneumoniae sequence type 258 (ST258) clone in an Italian hospital during two months in 2010. The rapid detection and management of the eleven patients colonized and infected with KPC-producing K.pneumoniae curbed the spread of this multidrug-resistant organism.


October 24, 2015 at 7:29 pm


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