The frequency of ESBL producing bacterial infections and related antimicrobial susceptibility in ICU patients: a five-year longitudinal study

Authors

Abstract

AimThis study aimed to evaluate the incidence of nosocomial infections caused by extended-spectrum β-lactamase (ESBL) producing bacteria and related antimicrobial susceptibility in critically ill patients over a 5-year period.
MethodsThe retrospective study was carried out in critically ill patients infected with ESBL-producing pathogens during intensive care unit (ICU) stay. Participants’ medical data between 2014 and 2018 were included. ESBL-positive isolates from clinical specimens were evaluated by species and antibiotic susceptibility.
ResultsNinety of 2456 critically ill patients had ESBL-positive bacterial infections. The mean age of the study sample was 58.7 ± 19.1 years and 53.3% were males. ESBL-producing E. coli was noted in 60 (66.7%) patients, K. pneumoniae in 27 (30.0%) patients and K. oxytoca in 3 (3.3%) patients. Colistin (100%), meropenem (94.9%), imipenem (94.0%), and amikacin (90.0%) were active against ≥90% of ESBL-producing pathogens, while ertapenem (89.4%), fosfomycin (87.5%), tigecycline (80.0%) were active against ≥80% of pathogens in ICU. Susceptibility of ESBL producers was remarkably low against levofloxacin (30.8%) and ciprofloxacin (36.7%). The mortality rate of the sample was 25.5%.
ConclusionOur findings revealed that ESBL-producing E. coli was highly responsible for ESBL-positive bacterial infections in ICU. The continued efficacy of colistin, carbapenems and amikacin against ESBL-producing E. coli and K. pneumoniae was exhibited.

Keywords

Introduction

The extended-spectrum beta-lactamase (ESBL) producing bacteria, particularly strains of Enterobacteriaceae, show resistance to several classes of antibiotics, limiting therapy choices in patients with nosocomial urinary tract infections (UTIs) and intraabdominal infections.^1,2,3,4 Hence, the critical rise in the worldwide prevalence of ESBL (+) Enterobacteriaceae is considered a great challenge in clinical practice given the associated risk of treatment failure, higher morbidity, longer hospital stay, and adverse patient outcomes.^5,6
Intensive care unit (ICU) patients are particularly prone to nosocomial infections due to vulnerability related to underlying critical illness, frequent use of invasive procedures, and exposure to antibiotics, in addition to limited treatment options due to multidrug-resistant (MDR) ESBL producers preventing provision of adequate treatment.^2,4,7,8,9
Given the variability in the prevalence of ESBL-producing strains and antimicrobial resistance rates in different geographic regions and over time, local surveillance studies are required to guide empiric treatment in accordance with the bacterial spectrum of pathogens and the extent of antimicrobial resistance.^6,9
This hospital-based descriptive study aimed to evaluate the frequency of ESBL-producing bacterial infections and related antimicrobial susceptibility in Anesthesiology and Medical ICU patients during a five-year period.

Materials and Methods

Study PopulationBetween 2014 and 2018, 2456 patients aged >18 years with nosocomial bacterial infection were screened. Critically ill patients infected with ESBL-producing bacteria during ICU stay were included in this hospital-based descriptive study conducted at ICUs of a tertiary care hospital during the study period.
The current study was approved by the local ethics committee. It was conducted in accordance with the Declaration of Helsinki.
AssessmentsData on participants’ demographics (age, gender), APACHE II score, comorbidities, risk factors of nosocomial infection due to ESBL-producing bacteria and clinical outcomes (need for mechanical ventilation (MV), ICU mortality) were recorded. ESBL-positive isolates from clinical specimens were assessed by species and susceptibility to antibiotics.
Definition of isolates and susceptibility testing
Identification of isolated bacteria was performed via conventional methods using VITEK® 2 Compact (bioMérieux, Marcyl’Etoile, France) system. Susceptibility testing was performed with the disc diffusion method in accordance with the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations. ESBL production of isolates was determined by double disc synergy method.
Ethical ApprovalEthics Committee approval for the study was obtained.
Statistical AnalysisDescriptive statistics were used. Continuous data were presented as “mean ± standard deviation or median (minimum-maximum) according to the normal distribution with the Shapiro-Wilk test. Categorical data were presented as numbers (percentage (%)).

Results

Demographic and Clinical Data of the Study SampleA total of n = 90 critically ill adult patients infected with ESBL-producing bacteria during ICU stay were included (Figure 1).
The mean patient age was 58.7 (SD: 19.1, range 18 to 96) years, and 53.3% of patients were male. The mean APACHE II score of the participants was 16.2 ± 7.1 (Table 1).
Pulmonary disease (14.4%), diabetes (13.3%), and hypertension (11.1%) were the most common comorbidities. Enteral nutrition (38.9%), transfusion (33.3%), and antibiotic use (25.5%) were the most common risk factors for developing nosocomial infection due to ESBL-producing bacteria. 55.6% of the participants needed MV treatment during the study period. ICU mortality was 25.5%, as shown in Table 1.
Esbl-Positive Isolates From Clinical Specimens by SpeciesOverall, ESBL producers isolated from clinical specimens included ESBL-producing E. coli in n = 60 (66.7%) patients, K. pneumoniae in n = 27 (30.0%) patients, and K. oxytoca in n = 3 (3.3%) patients (Figure 2).
Esbl-Positive Isolates From Clinical Specimens by Antibiotic Susceptibility**
Of the drugs studied, colistin (100%), meropenem (94.9%), imipenem (94.0%), and amikacin (90.0%) were active against ≥ 90% of nosocomial infections due to ESBL-producing bacteria. Only ertapenem (89.4%), fosfomycin (87.5%), and tigecycline (80.0%) were active against ≥ 80% of ESBL-producing bacteria (Table 2).
Susceptibility of ESBL-producing pathogens was remarkably low against levofloxacin (30.8%), ciprofloxacin (36.7%), and sulfamethoxazole-trimethoprim (37.5%). The ESBL (+) isolates from clinical specimens by antibiotic susceptibility of the study sample are shown in Table 2 in detail.

Discussion

This hospital-based descriptive study revealed that the frequency of ESBL-positive bacterial infections in tertiary care ICUs was 3.7% over a 5-year period. ESBL-producing E. coli (66.7%) and K. pneumoniae (33.3%) were the causative pathogens, and ICU mortality rate was 25.5%, with provision of enteral nutrition (38.9%) and blood transfusion (33.3%) being the main risk factors. Antimicrobial sensitivity testing revealed continued efficacy of colistin, carbapenems, and amikacin against ESBL-producing E. coli and K. pneumoniae, along with resistance to fluoroquinolones and sulfamethoxazole-trimethoprim.
Data from worldwide SMART studies revealed a sustained increase in ESBL-producing Enterobacteriaceae strains over time, indicating ESBL production rates for E. coli ranging from 1.2% to 64.9% and for K. pneumoniae from 9.5% to 46.8%.^6,10,11 High ESBL rates in Turkey have been consistently reported in multinational European studies such as the 2004 to 2010 Tigecycline Evaluation and Surveillance Trial (30.9%) and the Regional Resistance Surveillance study for 2011 (> 40.0%).^12,13 According to HITIT study data on 1196 gram-negative nosocomial isolates in Turkish hospitals (2004 to 2005), among blood isolates, E. coli (31.7% (33.3% in ICUs)) and K. pneumoniae (33.3%) were reported to produce ESBLs.⁹
Our findings indicate ESBL-positive E. coli or K. pneumoniae as key pathogens for ICU-related infections during the study period. In a past study conducted with n = 140 anesthesiology ICU patients in 2013 in Turkey, 41 (29.3%) patients were colonized with ESBL (+) E. coli (n = 39) or K. pneumoniae (n = 2), similar to our study. ESBL (+) E. coli or K. pneumoniae colonization was determined as an independent risk factor for nosocomial infection development.² SMART 2011 to 2012 Turkey data revealed ESBL (+) E. coli rates lower (29.2% versus 52.5%) but ESBL-positive K. pneumoniae rates higher (53.8% versus 39.6%) in ICU compared to non-ICU settings for intraabdominal infections.⁶ Authors also indicated ESBL-positive E. coli (49.0%) and K. pneumoniae (44.0%) rates to be higher in Turkey compared to global (2005 to 2007 and 2009 to 2010) and European (2002 to 2011) SMART rates,^14,15 compatible with regions with especially high ESBL rates (Asia, Latin America, Middle East).^11,16
In the current study, colistin, meropenem, imipenem, and amikacin were sensitive to ≥ 90% of ESBL-producing pathogens, while ertapenem, fosfomycin, and tigecycline were active against ≥ 80% of pathogens in ICU. Susceptibility was low against levofloxacin (30.8%), ciprofloxacin (36.7%), and sulfamethoxazole-trimethoprim (37.5%). SMART studies similarly showed carbapenems and amikacin highly susceptible to ESBL-producing E. coli and K. pneumoniae, with resistance against cephalosporins and fluoroquinolones emphasized.^{6,14,16,17,18}
Previous studies from Turkey also indicated low susceptibility to cephalosporins due to increased ESBL (+) rates among E. coli and K. pneumoniae, limiting empirical therapeutic options for UTI treatment of hospital-acquired infections.^6,19 Increased fosfomycin usage, particularly for hospital-acquired UTIs, has been noted due to low resistance (~ 1.6%), making it a suitable alternative for empirical treatment.^19,20
In a 2011 study from Turkey, ESBL production was identified in 37 (39%) of 95 E. coli and K. pneumoniae strains, particularly in ICU isolates (65%) versus clinic isolates (32%). Imipenem, meropenem, and ertapenem were effective in all strains, with higher resistance rates in ESBL-positive versus negative E. coli strains.²¹ In a 2010 to 2011 study from Turkey assessing 76 nosocomial ESBL-producing E. coli strains, most were isolated from ICU patients (35%), followed by internal medicine ward (16%) and general surgery unit (13%). All 76 strains were sensitive to carbapenems and amikacin.²²
In a study with 4680 isolates from critically ill patients and 16,263 isolates from non-critically ill patients collected from 70 US hospitals (2018 to 2020), ICU isolates were associated with lower antimicrobial susceptibility and higher ESBL, CRE, MDR, and XDR phenotypes.⁷ The most active agents against Enterobacteriaceae were ceftazidime-avibactam and meropenem-vaborbactam, maintaining strong activity against ESBL producers, CRE, MDR, and XDR isolates.⁷
A prospective study in India with n = 887 blood culture specimens from ICU patients with suspected sepsis reported microbial growth in 202 (22.78%) specimens. Gram-negative bacteria (E. coli most common) accounted for 45.2% of cases, with 77.3% of isolates being ESBL producers. Colistin and tigecycline sensitivity was evident in 66.7% and 71.4% of ESBL-positive isolates.²³
Accordingly, ESBL-producing E. coli and K. pneumoniae were responsible for nosocomial infections in most blood culture isolates from critically ill ICU patients. Our findings support considering multidrug resistance as a significant problem associated with increased hospital costs, ICU stay duration, and mortality.²³ Antimicrobial sensitivity findings are consistent with past studies indicating continued efficacy of carbapenems, amikacin, and fosfomycin against ESBL-producing E. coli and K. pneumoniae, along with resistance to fluoroquinolones and sulfamethoxazole-trimethoprim.^{6,7,14,16,17,18,24} Given the likelihood of emerging resistance in Enterobacteriaceae compromising carbapenem utility, carbapenem-sparing alternative antibiotics are considered highly important for treatment strategies. Carbapenems are suggested for severe, high inoculum, high-risk infections, while carbapenem-sparing antibiotics may be used for milder infections, particularly UTIs.²⁵
The retrospective and single-center design is the major limitation of our study, preventing generalization of data to all critically ill patients.

Conclusion

Our findings revealed that ESBL-producing E. coli were highly responsible for ESBL-positive bacterial infections in ICUs. Colistin, carbapenems, amikacin and fosfomycin have been shown to be consistently effective against ESBL-producing E. coli and K. pneumoniae. The resistance to fluoroquinolones and sulfamethoxazole-trimethoprim showed the risk of increase in ESBL-producing bacterial infections in terms of limited effective treatment options over time in critically ill patients.

Declarations

References

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About This Article

Received:

January 14, 2023

Accepted:

February 14, 2023

Published Online:

February 24, 2023

Printed:

March 25, 2023