Use of tigecycline for the treatment of prolonged bacteremia due to a multiresistant VIM-1 and SHV-12 β-lactamase–producing Klebsiella pneumoniae epidemic clone

doi:10.1016/j.diagmicrobio.2007.09.017

Diagnostic Microbiology and Infectious Disease

Volume 60, Issue 3, March 2008, Pages 319-322

https://doi.org/10.1016/j.diagmicrobio.2007.09.017 Get rights and content

Abstract

We report the use of tigecycline, firstly with colistin and finally alone, in a patient with a persistent breakthrough bacteremia due to a Klebsiella pneumoniae isolate harboring a metallo-β-lactamase (VIM-1) and an extended-spectrum β-lactamase (SHV-12). Time-kill studies demonstrated that the combination of both compounds was synergistic along the first 12 h, suppressing the regrowth observed after 3 to 6 h when colistin was tested alone.

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Acknowledgments

β-Lactamase identifications and time killing studies were performed through a research grant from Instituto de Salud Carlos III, Ministry of Health (FIS PI060806) and the Microbial Sciences Foundation (Madrid, Spain). M. Tato is a recipient of a contract from the Instituto de Salud Carlos III Spain (CM06/00044). The authors did not receive compensation for either their participation as investigators in this study or for the writing of this article.

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Evaluation of in vitro methods for testing tigecycline combinations against carbapenemase-producing Klebsiella pneumoniae isolates
2020, Journal of Global Antimicrobial Resistance
Treatment of infections caused by carbapenemase-producing Klebsiella pneumoniae (CPKP) frequently involves combination therapy with various antimicrobial agents in the hope of achieving synergistic effects. Routine laboratory antimicrobial synergy testing is a service that is currently unavailable owing to the laborious nature of the reference time–kill assay (TKA) as well as the widely used chequerboard method. In this study, we explored whether easier methods, based on the Etest technique, might offer a suitable alternative.
In vitro interactions of tigecycline combination with colistin, gentamicin, fosfomycin or meropenem against 26 CPKP isolates were evaluated employing the TKA, chequerboard method and three Etest methodologies (the MIC/MIC ratio, the cross formation and the agar/Etest method). Rates of consequent synergy and concordance of the studied methods were determined.
All antimicrobial combinations demonstrated some degree of synergy against the CPKP isolates tested. No antagonism was observed for any of the combinations. All methods showed poor synergy concordance with the TKA, producing non-significant kappa (κ) results. Etest methods (MIC/MIC ratio and agar/Etest) exhibited fair agreement (κ = 0.29 and 0.38, respectively) with the chequerboard method.
There is a poor correlation between synergy testing methods of tigecycline combinations, which may be associated with their different endpoints. To elucidate method comparability and reliability, their correlation with clinical outcomes appears important.
Emergence of carbapenemase-producing urinary isolates at a tertiary care hospital in Dhaka, Bangladesh
2016, Tzu Chi Medical Journal
A growing incidence of pathogens producing carbapenemases has been observed in many countries including Bangladesh. The present study was carried out to determine the presence of carbapenemase producers among uropathogens.
A total of 138 Gram-negative uropathogens were isolated and identified by conventional methods and were screened for carbapenemase production using imipenem discs. Phenotypic identification of carbapenemase production was done by the double disc synergy test, combined disc assay, and modified Hodge test. The minimum inhibitory concentration of imipenem was determined by the agar dilution method. Genes encoding blaNDM-1, blaIMP, blaVIM, blaKPC and blaOXA-48/blaOXA-181 were identified by polymerase chain reaction.
Twenty (14.49%) imipenem resistant strains were detected among 138 Gram-negative uropathogens. The most common isolates were Escherichia coli and Klebsiella spp. Among 20 imipenem resistant strains, 16 (80%) carbapenemase producers were detected by polymerase chain reaction, 13 (65%) by double disc synergy, 15 (75%) by combined disc assay, and seven (35%) by modified Hodge test. The blaNDM-1 gene was most prevalent (55%), followed by blaOXA-48/OXA-181, blaKPC (20%), blaVIM (15%), and blaIMP (10%). More than one carbapenemase gene was present in nine (45%) of the isolates. The minimum inhibitory concentration of imipenem of the carbapenemase producers ranged from ≥128 μg/mL to 4 μg/mL. Overall, carbapenemase encoding genes were detected in 11.6% (16/138) of the studied Gram-negative uropathogens. All (100%) of the carbapenemase-producing organisms were resistant to all tested antibiotics apart from colistin.
The study shows a significant rate of urinary isolates were carbapenemase producers, including a high prevalence of blaNDM-1, in Bangladesh.
Treatment of infections caused by carbapenemase-producing Enterobacteriaceae
2014, Enfermedades Infecciosas y Microbiologia Clinica
Treatment of infections caused by carbapenemase-producing Enterobacteriaceae (CPE) is currently one of the most important challenges of infectious diseases. The available information is based on in vitro studies, some animal model data and a few case studies and retrospective cohorts; appropriate data are lacking or are very scarce for some old antibiotics that are still occasionally used. Because of the heterogeneity in clinical situations, in specific carbapenemases and in the susceptibility of isolates, individualized treatment decisions must usually be made. Here we review the different antibiotics that might be useful for treating infections caused by CPE.
El tratamiento de las infecciones causadas por las enterobacterias productoras de carbapenemasas (EPC) es uno de los retos más difíciles de las enfermedades infecciosas en la actualidad. La información disponible se basa en estudios in vitro, modelos animales y un escaso número de series de casos y estudios de cohortes retrospectivos; no existen datos, o son escasos, para algunos de los antibióticos “viejos” que a veces deben usarse. Es habitual que deban tomase decisiones individualizadas debido a la heterogeneidad de situaciones clínicas, carbapenemasas específicas y sensibilidad de los aislados. En este artículo se revisan los diferentes antibióticos que pueden ser útiles para el tratamiento de las infecciones por ECP.
Infections Due to NDM-1 Producers
2014, Emerging Infectious Diseases: Clinical Case Studies
While antibiotic resistance is quickly rising in Gram-negative bacteria, the recent spread of a new resistance trait, namely, the New Delhi metallo-β-lactamase (NDM-1), represents an important medical issue. This carbapenemase compromises the efficacy of almost all β-lactams, including the last resort carbapenems. The transferable NDM-1 gene is identified in a variety of enterobacterial species, leading to multidrug resistance in Enterobacteriaceae. In particular, NDM-1-producing Klebsiella pneumoniae and Escherichia coli may cause severe nosocomial infections, including urinary tract infections, peritonitis, septicemia, and pulmonary infections. NDM-1 producers are the source of hospital and community-acquired infections, and are very difficult to control. Therapeutic options are limited to colistin, tigecycline, and fosfomycin. The main reservoirs of NDM producers are currently the Indian subcontinent, the Balkan states, and the Middle East. Rapid diagnostic techniques and isolation of infected patients and carriers are the main factors to try to contain this outbreak, which threatens the efficacy of modern medicine.
Klebsiella pneumoniae: Development of a mixed population of carbapenem and tigecycline resistance during antimicrobial therapy in a kidney transplant patient
2012, Clinical Microbiology and Infection
Nine isolates of Klebsiella pneumoniae were isolated from a renal transplant patient suffering from recurrent urosepsis over a period of 4 months. Imipenem resistance was detected after imipenem-ertapenem therapy. When treatment was switched to tigecycline the K. pneumoniae developed resistance to tigecycline (MIC = 8 mg/L). The nine isolates were tested by determination of agar dilution MICs, phenotypic carbapenemase, extended-spectrum beta-lactamases and metallo-beta-lactamase (MBL) testing and pulsed-field gel electrophoresis. Polymerase chain reaction and sequencing analysis were employed for identification of bla genes and mapping of the integron carrying the MBL gene. The nine isolates were clonally related and all produced the SHV-12 enzyme. Five MBL-producing isolates showed imipenem MICs ranging from 2 to 64 mg/L and all were detected by testing with imipenem and EDTA. The five isolates harboured the bla_VIM-1 gene. Three isolates showed increased tigecycline MICs (4–8 mg/L). Serial blood cultures obtained on the same day resulted in a VIM-positive/tigecycline-susceptible and a VIM-negative/tigecycline-resistant K. pneumoniae isolate. No isolate developed concurrent imipenem and tigecycline resistance. The patient had a persistent urinary tract infection and recurrent bacteraemia caused by a mixed population of Klebesiella pneumoniae isolates adapting to the selective pressure of antimicrobial therapy at the time. The present study is a worrisome example of what could happen when an immunocompromised host is subjected to the pressures of antimicrobial therapy. In addition, we report the first treatment-emergent MIC increase of tigecycline from 0.5 to 8 mg/L in K. pneumoniae.
Metallo-β-lactamases: A last frontier for β-lactams?
2011, The Lancet Infectious Diseases
Citation Excerpt :
In the Greek case series152 including 14 cases of bacteraemia and three cases of ventilator-associated pneumonia, which were caused by blaVIM-1-producing enterobacteria,152 tigecycline was active against all isolates. Tigecycline was also successfully used to treat a patient with prolonged bacteraemia that was caused by VIM-1-producing and SHV-12-producing K pneumonia.156 However, the low serum concentrations of tigecycline suggest the need for caution and careful assessment of the MIC values before using this drug for bloodstream infections.157
Metallo-β-lactamases are resistance determinants of increasing clinical relevance in Gram-negative bacteria. Because of their broad range, potent carbapenemase activity and resistance to inhibitors, these enzymes can confer resistance to almost all β-lactams. Since the 1990s, several metallo-β-lactamases encoded by mobile DNA have emerged in important Gram-negative pathogens (ie, in Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii). Some of these enzymes (eg, VIM-1 and NDM-1) have been involved in the recent crisis resulting from the international dissemination of carbapenem-resistant Klebsiella pneumoniae and other enterobacteria. Although substantial knowledge about the molecular biology and genetics of metallo-β-lactamases is available, epidemiological data are inconsistent and clinical experience is still lacking; therefore, several unsolved or debatable issues remain about the management of infections caused by producers of metallo-β-lactamase. The spread of metallo-β-lactamases presents a major challenge both for treatment of individual patients and for policies of infection control, exposing the substantial unpreparedness of public health structures in facing up to this emergency.

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Diagnostic Microbiology and Infectious Disease

Abstract

Section snippets

Acknowledgments

References (15)

Colistin-resistant isolates of Klebsiella pneumoniae emerging in intensive care unit patients: first report of a multiclonal cluster

J. Antimicrob. Chemother.

Combination of tigecycline and N-acetylcysteine reduces biofilm-embedded bacteria on vascular catheters

Antimicrob. Agents Chemother.

Performance Standards for Antimicrobial Susceptibility Testing; 17th Informational Supplement, M100-S17

Communiqué 2006

Genes encoding TEM-4, SHV-2, and CTX-M-10 extended-spectrum beta-lactamases are carried by multiple Klebsiella pneumoniae clones in a single hospital (Madrid, 1989 to 2000)

Antimicrob. Agents Chemother.

Antimicrobial combinations

EUCAST technical note on tigecycline

Clin. Microbiol. Infect.

Cited by (50)

Evaluation of in vitro methods for testing tigecycline combinations against carbapenemase-producing Klebsiella pneumoniae isolates

Emergence of carbapenemase-producing urinary isolates at a tertiary care hospital in Dhaka, Bangladesh

Treatment of infections caused by carbapenemase-producing Enterobacteriaceae

Infections Due to NDM-1 Producers

Klebsiella pneumoniae: Development of a mixed population of carbapenem and tigecycline resistance during antimicrobial therapy in a kidney transplant patient

Metallo-β-lactamases: A last frontier for β-lactams?

NotesUse of tigecycline for the treatment of prolonged bacteremia due to a multiresistant VIM-1 and SHV-12 β-lactamase–producing Klebsiella pneumoniae epidemic clone

Abstract

Section snippets

Acknowledgments

Colistin-resistant isolates of Klebsiella pneumoniae emerging in intensive care unit patients: first report of a multiclonal cluster

J. Antimicrob. Chemother.

Combination of tigecycline and N-acetylcysteine reduces biofilm-embedded bacteria on vascular catheters

Antimicrob. Agents Chemother.

Performance Standards for Antimicrobial Susceptibility Testing; 17th Informational Supplement, M100-S17

Communiqué 2006

Genes encoding TEM-4, SHV-2, and CTX-M-10 extended-spectrum beta-lactamases are carried by multiple Klebsiella pneumoniae clones in a single hospital (Madrid, 1989 to 2000)

Antimicrob. Agents Chemother.

Antimicrobial combinations

EUCAST technical note on tigecycline

Clin. Microbiol. Infect.

Notes
Use of tigecycline for the treatment of prolonged bacteremia due to a multiresistant VIM-1 and SHV-12 β-lactamase–producing Klebsiella pneumoniae epidemic clone