Antimicrobial Susceptibility Profiles of Microorganisms Isolated from Patients Treated in Intensive Care Units Before and During the COVID-19 Pandemic: A Single-center Retrospective Study

Abdulhamit ÇALI; Resul Ekrem AKBULUT; Rukiye ASLAN; Mürşit HASBEK; Ayse Hümeyra TAŞKIN KAFA

doi:10.14235/bas.galenos.2025.78989

ABSTRACT

Objective

The global coronavirus disease-2019 (COVID-19) pandemic has increased public health challenges, especially in intensive care units (ICU) where COVID-19 patients are at increased risk of infectious complications. This study aimed to identify, compare, and evaluate antimicrobial susceptibility profiles of microbial isolates from ICU patients of a tertiary hospital in Türkiye before and during the COVID-19 pandemic.

Methods

In this retrospective analysis, we analyzed data from 1462 patients who were admitted to the ICU of Sivas Cumhuriyet University Faculty of Medicine Application and Research Hospital between January 2018 and December 2022. In this analysis, demographic and clinical variables including age, gender, and antimicrobial susceptibility test results, as well as the annual distribution and antimicrobial resistance profiles of clinical isolates were determined.

Results

Among the 1687 sputum, 1396 urine, and 1307 blood cultures analyzed, there was a significant increase in sputum cultures during the pandemic (21.94%; p=0.012). The proportion of gram-negative bacteria was high in all cultures. Pseudomonas aeruginosa (P. aeruginosa) was common in sputum cultures, Escherichia coli (E. coli) in urine cultures, and coagulase-negative staphylococci (CoNS) in blood cultures. Gram-negative bacteria gradually increased in all cultures from 2018 to 2022. There was a decrease in gram-positive bacteria. In general, antibiotic resistance of P. aeruginosa and E. coli isolates increased before the pandemic but decreased during the pandemic.

Conclusion

Our study shows that infection profiles before and during the pandemic are different from each other. Continuous monitoring of resistance patterns will contribute to developing infection control strategies to prevent the development of antimicrobial resistance.

Keywords:

Antimicrobial resistance, intensive care unit, COVID-19, antimicrobial susceptibility profile

Introduction

Antimicrobial resistance is an important public health problem that is increasing daily (1). Uncontrolled use of antimicrobial agents in the treatment of infectious diseases is one of the leading factors causing the development of antimicrobial resistance (2). Nosocomial infections cause serious mortality and morbidity by prolonging the hospital stay of patients (3). Infections in intensive care units (ICUs) account for 25% of nosocomial infections (4). Patients hospitalized in ICUs are usually immunocompromised individuals who have undergone interventional procedures and receive broad-spectrum antibiotic treatment (2). Intensive use of antibiotics in ICUs is one of the leading factors in the emergence and development of antimicrobial resistance. Acinetobacter baumannii (A. baumannii), Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumoniae), methicillin-resistant Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Vancomycin-Resistant Enterococcus, Serratia marcescens, Enterobacter cloacae (E. cloacae) are among the microorganisms causing nosocomial infections (4, 5). Antimicrobial resistance profiles of the microorganisms causing these infections vary regionally (4). Identifying these microorganisms and determining their antimicrobial susceptibility profiles are essential for clinicians to control nosocomial infections and determine infectious disease treatment plans (6). With the emergence of the coronavirus disease-2019 (COVID-19) pandemic, researchers have warned of the risks of inappropriate antibiotic use and the risks that may occur, based on experience from past outbreaks (7). Especially the low immunity of patients treated in ICUs and the effect of invasive interventions applied to these patients cause an increased risk of infectious diseases in these patients. This leads to more antimicrobial agents (2). Monitoring and evaluating the use of antimicrobial agents in critical situations such as pandemics, where infectious diseases are widespread throughout society, is essential for the continuation of public health. As a result of research conducted in different countries, it is stated that the use of antimicrobial agents has increased during the COVID-19 pandemic (8). In this study, it was aimed to retrospectively investigate the microorganisms isolated from the samples sent to the microbiology laboratory and antimicrobial susceptibility profiles of patients who were being treated in the ICUs of Sivas Cumhuriyet University Faculty of Medicine Application and Research Hospital before and during the COVID-19 pandemic.

Methods

Study Design and Setting

In this study, we retrospectively analyzed the reports of patients treated in the ICU of Sivas Cumhuriyet University Faculty of Medicine Application and Research Hospital. The study was conducted to determine the resistance profiles of microorganisms isolated from sputum, urine, and blood cultures. Sivas Cumhuriyet University Faculty of Medicine Application and Research Hospital is a tertiary care teaching hospital with 1050 beds. We surveyed samples, demographic characteristics, and results of culture tests of patients treated in the ICU of the hospital between January 2018 and December 2022. In Türkiye, the period before this date was considered pre-pandemic since the pandemic was declared on March 11, 2020.

Inclusion Criteria

This study included isolates from sputum, urine, and blood culture samples. Two blood cultures with the same results were included in the study. The first samples from recurrent patient samples were accepted into the study, and the others were excluded. In addition, samples considered to be contaminated were excluded.

Bacterial Identification, and Antimicrobial Susceptibility Tests

Clinical isolates in the samples sent to the microbiology laboratory were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) using Microflex LT MALDI-TOF MS (Bruker Daltonics, Germany) according to the manufacturer’s operating procedures. Antimicrobial susceptibility tests of the identified bacterial isolates were analyzed using Phoenix 100® (Becton Dickinson, USA), and yeast isolates were analyzed using Micronaut (Bruker Daltonics, Germany) test kits according to the manufacturer’s procedures. Antimicrobial susceptibilities of the isolates were evaluated according to the European Committee on Antimicrobial Susceptibility Testing criteria (9).

Data Collection

Demographic information such as age, and gender, and clinical information such as antimicrobial susceptibility test results were collected from the electronic medical records of the hospital. This study was conducted in compliance with the Helsinki Declaration and informed consent was obtained from all participants before starting the study.

Ethical Principles of the Research

Before initiating the study, ethical permission for the research was obtained from the Sivas Cumhuriyet University Ethical Committee of Non-invasive Clinical Research (decision no: 2023-10/03, date: 19.10.2023).

Statistical Analysis

Statistical analyses were conducted using GraphPad Prism (version 8) software package. Descriptive analyses were presented using frequencies and percentages. Changes in antimicrobial resistance before and during the pandemic were analyzed using x² or Fisher’s exact test. The significance level was accepted at a p< 0.05.

Results

Demographics of the Study Population

As presented in Table 1, the study population was nearly equally distributed by sex and predominantly elderly. A total of 4405 microbiological culture results were included in the study (38.43% sputum, 32.8% urine, 29.77% blood). The sputum culture rate was higher in the pre-pandemic period (16.49%) than in pandemic period (21.94 %) (p=0.012).

Clinical Isolates

Gram-negative bacteria were the most frequently isolated microorganisms from sputum, urine, and blood cultures in the ICU. Gram-positive bacteria were more common in blood cultures (46.31%) than in sputum, and urine cultures. During the pandemic period, the proportion of gram-negative bacteria grown in sputum, urine, and blood cultures increased (77.26%, 75%, and 56.52%, respectively) (Table 2, Figure 1).

As shown in Figure 1 and Table 2, the dominant pathogens varied by specimen: P. aeruginosa, S. aureus and K. pneumoniae were common in sputum; E. coli, K. pneumoniae and Enterococcus faecium (E. faecium) in urine; and CoNS, K. pneumoniae and S. aureus in blood cultures.

Antimicrobial Resistance in Bacteria

Antimicrobial Resistance Profile of Gram-positive Bacteria

Antimicrobial resistance status of gram-positive bacteria commonly grown in sputum, urine, and blood cultures were analyzed. Overall, S. aureus isolates grown in sputum, urine and blood cultures were susceptible to vancomycin, teicoplanin, tigecycline and trimethoprim-sulfamethoxazole, but showed high resistance to penicillin (99.2% sputum; 100% urine; 99.0% blood cultures) and ampicillin (99.2% sputum; 100% urine; 99.1% blood cultures) (Figure 2).

E. faecium grown in urine culture showed increased resistance to teicoplanin (0.0% pre-pandemic; 14.3% pandemic; p=0.007) and decreased resistance to amoxicillin-clavulanate (97.9% pre-pandemic; 84.9% pandemic; p=0.032) during the pandemic (Figure 2).

Resistance to trimethoprim-sulfamethoxazole (9.8% pre-pandemic; 32.3% pandemic; p<0.001) and teicoplanin (3.9% pre-pandemic; 11.4% pandemic; p=0.031) increased, while resistance to clindamycin (69.6% pre-pandemic; 54.4% pandemic; p=0.008) decreased in CoNS grown in blood cultures. A decrease in amoxicillin-clavulanate (12.9% pre-pandemic; 0.0% pandemic; p=0.032) resistance was also observed in Enterococcus faecalis (E. faecalis) grown in blood cultures (Figure 2).

Antimicrobial Resistance of Gram-negative Bacteria

Antimicrobial resistance profiles of the most frequently grown six gram-negative bacteria in sputum, urine, and blood cultures are shown in Figure 2. During the pandemic, P. aeruginosa in sputum cultures showed a decrease in cephalosporin resistance (42.3% pre-pandemic; 27.6% pandemic; p<0.001) and an increase in gentamicin resistance (16.7% pre-pandemic; 47.6% pandemic; p<0.001). K. pneumoniae grown in sputum cultures showed a decrease in levofloxacin resistance (83.3% pre-pandemic; 60.6% pandemic; p<0.001). E. coli grown in sputum cultures showed decreasing resistance to β-lactam/adjuvant antibiotics (69.4% pre-pandemic; 44.1% pandemic; p<0.001) and ciprofloxacin (70.8% pre-pandemic; 50.5% pandemic; p=0.013). During the pandemic period, E. cloacae isolates were resistant to carbapenems (2.8% pre-pandemic; 39.4% pandemic; p<0.001) and ceftazidime (16.7% pre-pandemic; 61.9% pandemic; p=0.027), while Proteus mirabilis (P. mirabilis) isolates had increased resistance to cefuroxime (0.0% pre-pandemic; 19.05% pandemic; p=0.018) and gentamicin (25.9% pre-pandemic; 54.8% pandemic; p=0.034).

E. coli grown in urine cultures were resistant to trimethoprim-sulfamethoxazole (56.9% pre-pandemic; 43.6% pandemic; p=0.008), β-lactam/adjuvant (43.4% pre-pandemic; 28.7% pandemic; p<0.001), ampicillin (83.9% pre-pandemic; 71.1% pandemic; p=0.002) and ciprofloxacin (55.4% pre-pandemic; 44.1% pandemic; p=0.025) significantly decreased during the pandemic period. However, resistance to ceftazidime (44.3% pre-pandemic; 88.9% pandemic; p<0.001) increased. Ceftazidime (75.2% pre-pandemic; 98.5% pandemic; p<0.001) resistance of K. pneumoniae grown in urine cultures increased, while levofloxacin (90.9% pre-pandemic; 61.5% pandemic; p<0.001) resistance decreased. Piperacillin/tazobactam (62.7% pre-pandemic; 3.4% pandemic; p<0.001) and ceftazidime (47.1% pre-pandemic; 12.7% pandemic; p<0.001) resistance of P. aeruginosa isolates grown in urine cultures decreased during the pandemic period. Trimethoprim-sulfamethoxazole (57.8% pre-pandemic; 81.8% pandemic; p=0.025) resistance of P. mirabilis isolates increased.

In blood cultures, piperacillin/tazobactam (47.1% pre-pandemic; 37.7% pandemic; p=0.001) and ceftazidime (37.7% pre-pandemic; 19.0% pandemic; p=0.002) resistance of P. aeruginosa decreased, while tigecycline (8.3% pre-pandemic; 33.3% pandemic; p<0.001) resistance of E. coli increased.

Annually Antimicrobial Resistance Distribution of Clinical Isolates

As shown in Figure 3, the annual variation in antibiotic resistance rates of P. aeruginosa, E. coli, and K. pneumoniae isolates frequently grown in sputum, urine, and blood cultures were analyzed.

In all types of cultures, β-lactam/adjuvant antibiotic resistance in P. aeruginosa isolates across all cultures decreased after 2019. Resistance to fluoroquinolones steadily increased before the pandemic but showed a continuous decrease during the pandemic period. Nevertheless, fluoroquinolones resistance rates in sputum and urine cultures in 2022 were higher than those in 2018. Carbapenem resistance in isolates from sputum cultures increased before the pandemic but remained stable during the pandemic period. The highest carbapenem resistance in isolates from blood cultures was observed in 2021. Cephalosporin resistance in isolates from sputum cultures decreased from 48.42% in 2019 to 24.78% in 2022, while the resistance rate in urine cultures decreased to 8% in 2022. Cephalosporin resistance rate in blood cultures decreased from 51.72% in 2019 to 17.5% in 2022. The resistance of P. aeruginosa isolates to aminoglycosides increased from 2018 to 2020, but after 2020; it decreased again to the resistance rates observed in 2018 (Figure 3).

While the antifolate, cephalosporins, and aminoglycosides resistance of E. coli isolates grown in urine and blood cultures increased before the pandemic, it decreased to its lowest rate in 2021 and then rose again in 2022. Specifically, antifolate resistance decreased from 60% to 36% in urine isolates and from 66.6% to 29.4% in blood isolates. Similarly, cephalosporin resistance dropped from 56.8% to 48.6% in urine and from 57.1% to 23.6% in blood samples. For aminoglycosides, resistance fell from 12% to 6.4% in urine cultures and from 25% to 5.5% in blood cultures. Antifolate resistance rate of E. coli isolates in sputum cultures was the highest (67%) in 2019 and decreased to the lowest level (35%) in 2022. Additionally, the rate of cephalosporin resistance in sputum cultures decreased from 57.7% in 2020 to 23.5% in 2022. There was no significant change in aminoglycoside resistance. While the β-lactam/adjuvant, and fluoroquinolone resistance rates of E. coli isolates growing in all cultures were highest in the pre-pandemic period, they decreased during the pandemic. Resistance rates of E. coli isolates to carbapenems were the lowest compared to other antimicrobials. In 2019, carbapenem resistance (22.6%) increased in sputum isolates (Figure 3).

There was no significant change in the antifolate resistance of K. pneumoniae isolates grown in sputum cultures. In urine and blood cultures, antifolate resistance increased in a fluctuating manner. The distribution of β-lactam/adjuvant antibiotic resistance in K. pneumoniae isolates grown in all culture types showed a similar pattern. Fluoroquinolone resistance distribution was similar across all culture types. The highest fluoroquinolone resistance was observed in isolates obtained from urine cultures, with a rate of 91.1% in 2019. Carbapenem resistance of isolates grown in sputum, urine, and blood cultures increased gradually over the years. In 2022, the resistance rates were 62.8%, 50%, and 56.4%, respectively. Cephalosporin resistance rates decreased during the pandemic period; however, an increase started to occur again in 2022. The aminoglycoside resistance rates of K. pneumoniae isolates grown in sputum, urine, and blood cultures were 9.3%, 13.9%, and 7.7%, respectively, in 2018. However, in 2022, the resistance rates had increased to 48.9%, 36.1%, and 42.3%, respectively (Figure 3).

Antimicrobial Resistance in Fungi

Antimicrobial resistance of Candida albicans (C. albicans) and other Candida isolated from urine and blood cultures were analyzed. C. tropicalis, C. glabrata, C. parapsilosis, and C. krusei were included among another Candida. Although the resistance rates of C. albicans isolates grown in urine cultures to azoles (43.8% pre-pandemic; 37.5% pandemic; p=0.341), echinocandins (17.7% pre-pandemic; 10.0% pandemic; p=0.432), and amphotericin B (2.0% pre-pandemic; 0.0% pandemic; p>0.999) decreased during the pandemic period, there was no significant change (Figure 4). On the other hand, the resistance rates of C. albicans isolates grown in blood culture to azoles (32.14% pre-pandemic; 70.8% pandemic; p=0.012) and echinocandins (7.7% pre-pandemic; 25.0% pandemic; p=0.321) increased during the pandemic period. All blood culture isolates were susceptible to amphotericin B (Figure 4).

Discussion

Antibiotic resistance poses a significant global public health threat and leads to increased mortality, hospitalizations, and prolonged hospital stays due to infections caused by resistant bacteria (1). The emergence of the COVID-19 pandemic has put great pressure on healthcare systems and led to a significant increase in empirical antibiotic treatments, especially among intensive-care patients (10). Despite this increase in antibiotic use, our study did not observe an overall significant increase in resistance development during the pandemic, consistent with findings in Taiwan however, a notable exception was noted in K. pneumoniae showing an increase in resistance during this period, which is consistent with findings from a separate study (10, 11).

Our study revealed a significant increase in the number of sputum cultures during the pandemic, possibly attributable to the increased frequency of respiratory sampling required by the pandemic. Gram-negative bacteria were isolated more frequently than gram-positive bacteria in all cultures, which is consistent with previous studies conducted in ICU patients (12, 13). Consistent with previous studies, P. aeruginosa was found to be the most frequently isolated bacterium from sputum samples in our study (14, 15). Urinary tract infections constitute an important part of nosocomial infections in ICU settings (16). In our study, E. coli and K. pneumoniae were the most frequently isolated bacteria in urine cultures to previous findings (17, 18). Bloodstream infections constitute an important burden on human health and the most frequently isolated organism in our study was CoNS, followed by S. aureus and P. aeruginosa; this is consistent with similar studies showing that gram-positive bacteria are predominant in blood cultures (19, 20).

Regarding antimicrobial resistance patterns, our findings revealed that S. aureus isolates were susceptible to trimethoprim-sulfamethoxazole, vancomycin, teicoplanin, and tigecycline and showed marked resistance to ampicillin which was also shown in previous studies (12). In contrast, we observed a significant increase in trimethoprim-sulfamethoxazole and teicoplanin resistance and a significant decrease in clindamycin resistance rate among CoNS isolated from blood cultures. Teicoplanin resistance also increased in a post-COVID-19 study, consistent with our findings (11).

Similar to the findings of a study conducted in Romania, a decrease in penicillin resistance among Enterococcus species was observed in our study. Furthermore, consistent with the study conducted in Colombia, an increase in vancomycin and teicoplanin resistance was recorded among E. faecium isolates (11, 21).

The resistance rates of A. baumannii isolates to antifolates, carbapenems, fluoroquinolones, and aminoglycosides were found to be quite high in other studies (22). Specifically, no significant change in antimicrobial resistance was observed among A. baumannii isolates in our study.

Regarding P. aeruginosa isolates, our study revealed a significant decrease in piperacillin-tazobactam and ceftazidime resistance in isolates obtained from blood and urine cultures. However, in sputum culture isolates, resistance to ceftazidime and cefepime decreased significantly, while gentamicin resistance showed a significant increase. These findings are consistent with another study covering the years 2016-2020, which observed a decrease in resistance rates in many antibiotic groups, except amikacin, in P. aeruginosa strains during the pandemic period (23).

In terms of E. coli isolates our study showed a significant decrease in resistance to antifolate, β-lactam/adjuvant antibiotics, ciprofloxacin, and ampicillin during the pandemic period. However, resistance to ceftazidime increased. Similarly, as reported in other studies on K. pneumoniae isolates; a high level of ampicillin resistance was found in our study (17, 18). In particular, K. pneumoniae exhibited a high resistance rate against many commonly used antimicrobials. While ceftazidime resistance increased in our study, levofloxacin resistance decreased significantly. Unlike our study, there is another study showing an increase in levofloxacin resistance (11).

Regarding fungal infections, C. albicans was the most frequently isolated yeast fungus in our study, which is consistent with previous studies showing its prevalence, especially in ICU patients (24). C. albicans isolates obtained from urine cultures generally showed decreased antimicrobial resistance during the pandemic, while those obtained from blood cultures showed increased resistance.

Despite the valuable data provided by our study, some limitations should be noted, including small sample sizes for some isolates and limitations in generalizing the findings due to the single-center nature of the study. Nevertheless, our study highlights the importance of comprehensive research on antimicrobial resistance patterns both before and during pandemics and provides valuable information to address this global health challenge.

Conclusion

While most of the microorganisms analyzed (S. aureus, C. striatum, A. baumannii, E. faecalis) showed no significant change in resistance patterns before and during the pandemic, P. aeruginosa and E. coli isolates showed a downward trend, while K. pneumoniae showed an increase in resistance after 2022. This is thought to be due to the irrational use of antibiotics. In addition to the development of strategies for the control of infectious diseases, it is necessary to raise awareness among healthcare professionals and the public on the rational use of antibiotics. Furthermore, further research is needed to elucidate the development of antimicrobial resistance.

Ethics

Ethical Committee Approval: Each stage of the study was conducted with ethical principles. Before initiating the study, written permission was obtained from the Sivas Cumhuriyet University Ethical Committee of Non-invasive Clinical Research (decision no: 2023-10/03, date: 19.10.2023).

Informed Consent: This study was conducted in compliance with the Helsinki Declaration and informed consent was obtained from all participants before starting the study.

Author Contribution: Concept: A.Ç., R.E.A., R.A., Design: A.Ç., R.E.A., R.A., Data Collection or Processing: A.Ç., R.E.A., Analysis or Interpretation: A.Ç., R.E.A., R.A., Literature Search: A.Ç., R.E.A., R.A., M.H., A.H.T.K., Writing: A.Ç., R.E.A., R.A., M.H., A.H.T.K.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.

References

Centers for Disease Control and Prevention. Antibiotic resistance threatens, centers for disease control and preventation. Published online 2022.

da Silva RMR, de Mendonça SCB, Leão IN, Dos Santos QN, Batista AM, Melo MS, et al. Use of monitoring indicators in hospital management of antimicrobials. BMC Infect Dis. 2021;21:827.

DiGiovine B, Chenoweth C, Watts C, Higgins M. The attributable mortality and costs of primary nosocomial bloodstream infections in the intensive care unit. Am J Respir Crit Care Med. 1999;160:976-81.

Fridkin SK, Welbel SF, Weinstein RA. Magnitude and prevention of nosocomial infections in the intensive care unit. Infect Dis Clin North Am. 1997;11:479-96.

Jeon J, Park JH, Yong D. Efficacy of bacteriophage treatment against carbapenem-resistant Acinetobacter baumannii in Galleria mellonella larvae and a mouse model of acute pneumonia. BMC Microbiol. 2019;19:1-14.

Spencer RC. Epidemiology of infection in ICUs. Intensive Care Med. 1994;20(Suppl 4):S2-6.

Chung DR, Huh K. Novel pandemic influenza A (H1N1) and community-associated methicillin-resistant Staphylococcus aureus pneumonia. Expert Rev Anti Infect Ther. 2015;13:197-207.

Ng TM, Tan SH, Heng ST, Tay HL, Yap MY, Chua BH, et al. Effects of coronavirus disease 2019 (COVID-19) pandemic on antimicrobial prevalence and prescribing in a tertiary hospital in Singapore. Antimicrob Resist Infect Control. 2021;10:28.

EUCAST. European committee on antimicrobial susceptibility testing. Eur Comm Antimicrob Susceptibility Test EUCAST. Published online 2021:0-114.

Chang HC, Chang CH, Tien KL, Tai CH, Lin LM, Lee TF, et al. Impact of coronavirus disease 2019 (COVID-19) on antimicrobial resistance among major pathogens causing healthcare-associated infection. J Formos Med Assoc. 2024;123:123-32.

Golli AL, Zlatian OM, Cara ML, Olteanu M. Pre- and post-covid-19 antimicrobial resistance pattern of pathogens in an intensive care unit. Pharmaceuticals (Basel). 2024;17:407.

Kabrah AM, Kabrah SM, Bahwerth FS, Alredaini NF. Antibiotic resistance profile of common bacteria isolated from blood stream, lower respiratory tract and urinary infections in intensive care unit in Saudi Arabia: a retrospective study. Ethiop J Health Sci. 2021;31:1231-40.

Vincent JL, Sakr Y, Singer M, Martin-Loeches I, Machado FR, Marshall JC, et al. Prevalence and outcomes of infection among patients in intensive care units in 2017. JAMA. 2020;323:1478-87.

Foschi C, Zignoli A, Gaibani P, Vocale C, Rossini G, Lafratta S, et al. Respiratory bacterial co-infections in intensive care unit-hospitalized COVID-19 patients: conventional culture vs BioFire FilmArray pneumonia plus panel. J Microbiol Methods. 2021;186:106259.

Caméléna F, Moy AC, Dudoignon E, Poncin T, Deniau B, Guillemet L, et al. Performance of a multiplex polymerase chain reaction panel for identifying bacterial pathogens causing pneumonia in critically ill patients with COVID-19. Diagn Microbiol Infect Dis. 2021;99:115183.

Saint S, Greene MT, Krein SL, Rogers MA, Ratz D, Fowler KE, et al. A program to prevent catheter-associated urinary tract infection in acute care. N Engl J Med. 2016;374:2111-9.

İgan H, Hancı H. Distribution of microorganisms and antibiotic resistance of gram-negative bacteria isolated from urine cultures of intensive care unit patients during the last four years. Turk J Intensive Care. 2022;20:25-30.

Keskin BH, Çalışkan E, Kaya S, Köse E, Şahin İ. Bacteria that cause urinary system infections and antibiotic resistance rates. Türk Mikrobiyoloji Cemiy Derg. 2021;51.

Aytaç Ö, Şenol FF, Şenol A, Öner P, Toraman ZA. COVID-19 Pandemisi öncesi ve sırasında yoğun bakım ünitesi hastalarından alınan kan kültürü izolatlarının tür dağılımı ve antibiyotik duyarlılık profillerinin karşılaştırılması. Türk Mikrobiyoloji Cemiy Derg. 2022;52:39-47.

Kassaian N, Nematbakhsh S, Yazdani M, Rostami S, Nokhodian Z, Ataei B. Epidemiology of bloodstream infections and antimicrobial susceptibility pattern in ICU and non-ICU wards: a four-year retrospective study in Isfahan, Iran. Adv Biomed Res. 2023;12:106.

Hurtado IC, Valencia S, Pinzon EM, Lesmes MC, Sanchez M, Rodriguez J, et al. Antibiotic resistance and consumption before and during the COVID-19 pandemic in Valle del Cauca, Colombia. Rev Panam Salud Publica. 2023;47:e10.

Arslan K. Clinical characteristics, antibiotic resistance profiles, and factors affecting mortality in patients isolated acinetobacter baumannii in intensive care unit: retrospective tertiary center analysis. Compr Med. 2024;16:51-7.

Habiloğlu AD, Şentürk GÇi̇, Gürbüz Y, et al. The effect of antibiotic use on microorganism distribution and antibiotic resistance in nosocomial infections in the Covid-19 pandemic. Turk Hij Ve Deney Biyol Derg. 2022;79(2):175-86.

Bilal H, Zhang D, Shafiq M, Khan MN, Chen C, Khan S, et al. Six-year retrospective analysis of epidemiology, risk factors, and antifungal susceptibilities of candidiasis from a Tertiary Care Hospital in South China. Microbiol Spectr. 2023;11(4).