Clinical Management of CUTI, CIAI, and HABP/VABP Attributable to Carbapenem-resistant Gram-negative Infections in Spain

Overview

Journal Rev Esp Quimioter

Specialty Pharmacology

Date 2021 Nov 22

PMID 34806858

Citations 1

Authors

R Ferrer

M C Farinas

E Maseda

M Salavert

G Bou

J Diaz-Reganon

D Lopez

V Lozano

D Gomez-Ulloa

R Fenoll

N Lara

E McCann

Affiliations

Soon will be listed here.

Abstract

Objective: Carbapenem-resistant Gram-negative (CRGN) infections are a major public health problem in Spain, often implicated in complicated, healthcare-associated infections that require the use of potentially toxic antibacterial agents of last resort. The objective of this study was to assess the clinical management of complicated infections caused by CRGN bacteria in Spanish hospitals.

Methods: The study included: 1) a survey assessing the GN infection and antibacterial susceptibility profile in five participating Spanish hospitals and 2) a non-interventional, retrospective single cohort chart review of 100 patients with complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP) attributable to CRGN pathogens.

Results: In the participating hospitals CRGN prevalence was 9.3% amongst complicated infections. In the retrospective cohort, 92% of infections were healthcare-associated, and Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common pathogens. OXA was the most frequently detected carbapenemase type (71.4%). We found that carbapenems were frequently used to treat cUTI, cIAI, HABP/VABP caused by CRGN pathogens. Carbapenem use, particularly in combination with other agents, persisted after confirmation of carbapenem resistance. Clinical cure was 66.0%, mortality during hospitalization 35.0%, mortality at the time of chart review 62.0%, and 6-months-post-discharge readmission 47.7%.

Conclusions: Our results reflect the high burden and unmet needs associated with the management of complicated infections attributable to CRGN pathogens in Spain and highlight the urgent need for enhanced clinical management of these difficult-to-treat infections.

Citing Articles

Participant- and Disease-Related Factors as Independent Predictors of Treatment Outcomes in the RESTORE-IMI 2 Clinical Trial: A Multivariable Regression Analysis.

Martin-Loeches I, Shorr A, Kollef M, Du J, Losada M, Paschke A Open Forum Infect Dis. 2023; 10(6):ofad225.

PMID: 37383243 PMC: 10297016. DOI: 10.1093/ofid/ofad225.

References

Munez Rubio E, Ramos Martinez A, Fernandez Cruz A . Fosfomycin in antimicrobial stewardship programs. Rev Esp Quimioter. 2019; 32 Suppl 1:62-66. PMC: 6555160. View

Peleg A, Hooper D . Hospital-acquired infections due to gram-negative bacteria. N Engl J Med. 2010; 362(19):1804-13. PMC: 3107499. DOI: 10.1056/NEJMra0904124. View

Grau S, Fondevilla E, Echeverria-Esnal D, Alcorta A, Limon E, Gudiol F . Widespread increase of empirical carbapenem use in acute care hospitals in Catalonia, Spain. Enferm Infecc Microbiol Clin (Engl Ed). 2018; 37(1):36-40. DOI: 10.1016/j.eimc.2018.03.003. View

Oviano M, Sparbier K, Barba M, Kostrzewa M, Bou G . Universal protocol for the rapid automated detection of carbapenem-resistant Gram-negative bacilli directly from blood cultures by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS). Int J Antimicrob Agents. 2016; 48(6):655-660. DOI: 10.1016/j.ijantimicag.2016.08.024. View

Knaus W, Draper E, Wagner D, Zimmerman J . APACHE II: a severity of disease classification system. Crit Care Med. 1985; 13(10):818-29. View

Canton R, Huarte R, Morata L, Trillo-Mata J, Munoz R, Gonzalez J . Determining the burden of infectious diseases caused by carbapenem-resistant gram-negative bacteria in Spain. Enferm Infecc Microbiol Clin (Engl Ed). 2020; 39(4):179-183. DOI: 10.1016/j.eimc.2020.04.009. View

Lusignani L, Presterl E, Zatorska B, Van den Nest M, Diab-Elschahawi M . Infection control and risk factors for acquisition of carbapenemase-producing enterobacteriaceae. A 5 year (2011-2016) case-control study. Antimicrob Resist Infect Control. 2020; 9(1):18. PMC: 6969403. DOI: 10.1186/s13756-019-0668-2. View

Vargas-Alzate C, Higuita-Gutierrez L, Lopez-Lopez L, Cienfuegos-Gallet A, Quiceno J . High excess costs of infections caused by carbapenem-resistant Gram-negative bacilli in an endemic region. Int J Antimicrob Agents. 2017; 51(4):601-607. DOI: 10.1016/j.ijantimicag.2017.12.012. View

Shields R, Clancy C, Hao B, Chen L, Press E, Iovine N . Effects of Klebsiella pneumoniae carbapenemase subtypes, extended-spectrum β-lactamases, and porin mutations on the in vitro activity of ceftazidime-avibactam against carbapenem-resistant K. pneumoniae. Antimicrob Agents Chemother. 2015; 59(9):5793-7. PMC: 4538547. DOI: 10.1128/AAC.00548-15. View

10.

Martin-Loeches I, Diaz E, Valles J . Risks for multidrug-resistant pathogens in the ICU. Curr Opin Crit Care. 2014; 20(5):516-24. DOI: 10.1097/MCC.0000000000000124. View

11.

Ruiz J, Ramirez P, Villarreal E, Gordon M, Sanchez M, Martin M . Effect of pharmacokinetic/pharmacodynamic ratio on tigecycline clinical response and toxicity in critically ill patients with multidrug-resistant Gram-negative infections. SAGE Open Med. 2020; 8:2050312120958897. PMC: 7506777. DOI: 10.1177/2050312120958897. View

12.

Katchanov J, Asar L, Klupp E, Both A, Rothe C, Konig C . Carbapenem-resistant Gram-negative pathogens in a German university medical center: Prevalence, clinical implications and the role of novel β-lactam/β-lactamase inhibitor combinations. PLoS One. 2018; 13(4):e0195757. PMC: 5896976. DOI: 10.1371/journal.pone.0195757. View

13.

Castanheira M, Mills J, Farrell D, Jones R . Mutation-driven β-lactam resistance mechanisms among contemporary ceftazidime-nonsusceptible Pseudomonas aeruginosa isolates from U.S. hospitals. Antimicrob Agents Chemother. 2014; 58(11):6844-50. PMC: 4249397. DOI: 10.1128/AAC.03681-14. View

14.

Nordmann P, Poirel L . Epidemiology and Diagnostics of Carbapenem Resistance in Gram-negative Bacteria. Clin Infect Dis. 2019; 69(Suppl 7):S521-S528. PMC: 6853758. DOI: 10.1093/cid/ciz824. View

15.

Carrer A, Poirel L, Yilmaz M, Akan O, Feriha C, Cuzon G . Spread of OXA-48-encoding plasmid in Turkey and beyond. Antimicrob Agents Chemother. 2010; 54(3):1369-73. PMC: 2825965. DOI: 10.1128/AAC.01312-09. View

16.

Paul M, Daikos G, Durante-Mangoni E, Yahav D, Carmeli Y, Dishon Benattar Y . Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial. Lancet Infect Dis. 2018; 18(4):391-400. DOI: 10.1016/S1473-3099(18)30099-9. View

17.

Hernandez-Garcia M, Perez-Viso B, Carmen Turrientes M, Diaz-Agero C, Lopez-Fresnena N, Bonten M . Characterization of carbapenemase-producing Enterobacteriaceae from colonized patients in a university hospital in Madrid, Spain, during the R-GNOSIS project depicts increased clonal diversity over time with maintenance of high-risk clones. J Antimicrob Chemother. 2018; 73(11):3039-3043. DOI: 10.1093/jac/dky284. View

18.

Marston H, Dixon D, Knisely J, Palmore T, Fauci A . Antimicrobial Resistance. JAMA. 2016; 316(11):1193-1204. DOI: 10.1001/jama.2016.11764. View

19.

Martin A, Fahrbach K, Zhao Q, Lodise T . Association Between Carbapenem Resistance and Mortality Among Adult, Hospitalized Patients With Serious Infections Due to : Results of a Systematic Literature Review and Meta-analysis. Open Forum Infect Dis. 2018; 5(7):ofy150. PMC: 6054228. DOI: 10.1093/ofid/ofy150. View