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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 9  |  Issue : 1  |  Page : 12-18

Nosocomial infections-related antimicrobial resistance in a multidisciplinary intensive care unit


1 Department of Medicine, ESIC Postgraduate Institute of Medical Sciences and Research, New Delhi, India
2 Indian Council of Medical Research (ICMR), New Delhi, India
3 Department of Pharmaceutical Science, Maharshi Dayanand University, Rohtak, Haryana, India

Date of Submission27-Dec-2021
Date of Acceptance17-Feb-2022
Date of Web Publication23-Mar-2022

Correspondence Address:
Dr. Shweta Tanwar
Indian Council of Medical Research (ICMR), New Delhi.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mgmj.mgmj_110_21

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  Abstract 

Background: Intensive care units (ICUs) have become hubs of nosocomial infections worldwide. There has been a continuous rise in the development of antimicrobial resistance among ICU-acquired infections. Particularly, the Gram-negative bacteria implicated in ICU-acquired infections have become resistant to the majority of the antibiotics leading to a critical therapeutic problem. The present study was conducted to determine the antimicrobial resistance pattern of microorganisms causing nosocomial infections (ventilator-associated pneumonia [VAP], central line-associated bloodstream infection [CLABSI], and catheter-associated urinary tract infection [CAUTI]) in a multidisciplinary ICU. Materials and Methods: This prospective observational cohort study included the patients with ICU stay ≥ 48 h and any of the ICU-acquired infections: VAP, CLABSI, or CAUTI. The appropriate specimen was collected as per the standard procedure and cultured. The antimicrobial susceptibility of all the bacterial isolates recovered from the samples was performed according to the Clinical and Laboratory Standards Institute (CLSI) recommendations. The antimicrobial resistance data were analyzed using WHONET Microbiology Laboratory Database software 5.6 (WHONET 5.6). Results: Gram-negative microorganisms were the principal pathogens causing various infections in the ICU, out of which Pseudomonas aeruginosa and Klebsiella pneumonia were the commonest. Most of the Gram-negative bacteria showed a high degree of resistance to the majority of the antibiotics. Colistin was observed to be the most effective antimicrobial for Gram-negative pathogens followed by doripenem, meropenem, and tigecycline. The majority of Staphylococcus aureus isolates (71.4%) were methicillin-resistant S. aureus; however, all were sensitive to vancomycin and linezolid. Vancomycin-resistant Enterococci constituted 43% of Enterococcus isolates and were sensitive to linezolid and tigecycline. Conclusion: Antimicrobial resistance was very high among the pathogens causing nosocomial infections in the ICU, especially Gram-negative bacteria demonstrated a substantially high degree of resistance to the majority of the antibiotics. Antibiotic stewardship will help control the emergence of multidrug-resistant microbes.

Keywords: Antibiotic resistance, Gram-negative bacteria, intensive care unit, nosocomial infections


How to cite this article:
Kumar A, Tanwar S, Chetiwal R, Kumar R. Nosocomial infections-related antimicrobial resistance in a multidisciplinary intensive care unit. MGM J Med Sci 2022;9:12-8

How to cite this URL:
Kumar A, Tanwar S, Chetiwal R, Kumar R. Nosocomial infections-related antimicrobial resistance in a multidisciplinary intensive care unit. MGM J Med Sci [serial online] 2022 [cited 2022 May 18];9:12-8. Available from: http://www.mgmjms.com/text.asp?2022/9/1/12/340580




  Introduction Top


The emergence of multidrug-resistant microbes has posed a significant threat to global health. Particularly, intensive care unit (ICU)-acquired infections are associated with multidrug-resistant bacteria. This leads not only to increased morbidity and mortality but also puts a considerable burden on the already constrained resources. Patients in ICUs are more prone to develop nosocomial infections owing to the use of multiple invasive devices, immunocompromised state, severe underlying diseases, and indiscriminate use of antibiotics. The most common bacteria implicated in nosocomial infections are Acinetobacter baumannii, Pseudomonas aeruginosa,Clostridium difficile, C. sordellii, extended-spectrum beta-lactamase (ESBL)-producing and carbapenemase-producing Enterobacterales (CPE), vancomycin-resistant Enterococci (VRE), Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA], vancomycin-intermediate S. aureus, and vancomycin-resistant S. aureus).[1] The development of bacterial resistance in the ICUs can be more challenging as the use of second-and third-line treatments can have serious side effects for the patients and it also prolongs the ICU length of stay and recovery. Although nosocomial infections constitute a global problem, most of the studies on these infections, their causative bacteria, and the antibiotic susceptibility pattern have been conducted in developed countries. There is an urgent need for international data related to these infections to develop international guidelines. The burden of infectious diseases in India is the highest in the world and according to recent reports, there has been an increase in the development of antimicrobial resistance due to inappropriate and irrational use of broad-spectrum antibiotics.[2] In this context, the present study was conducted to study the microbiological profile and resistance pattern of nosocomial infections in a multidisciplinary ICU.


  Materials and methods Top


A prospective observational cohort study was conducted in the multidisciplinary ICU in a tertiary care teaching hospital over 20 months. Prior approval was obtained from the Institutional Ethics Committee. Patients with ICU stay ≥ 48 h and who develop any of the nosocomial infection, VAP (ventilator-associated pneumonia), CLABSI (central line-associated bloodstream infection), or CAUTI (catheter-associated urinary tract infection), were included in the study. Informed consent was obtained. Exclusion criteria constituted ICU stay <48 h, age <18 or >80 years, transferred in from other ICUs, readmission to the ICU, admitted with burns, known HIV seropositivity, or with solid organ/bone marrow transplantation. Whenever an infection was suspected, appropriate specimen (trachea-bronchial secretions, bronchoalveolar lavage, blood, urine, catheter tips) was collected using the standard protocol. Standard microbiological methods based on growth conditions and appearance on solid media, assimilation, degradation, fermentation of sugars, and other organic compounds were used to identify the causative microorganism. Antimicrobial susceptibility testing of all the bacterial isolates recovered from the samples was performed by the Kirby–Bauer disc diffusion method, broth microdilution, Etest strip (antimicrobial gradient method), and VITEK 2 (automated broth-based testing), according to the Clinical and Laboratory Standards Institute (CLSI) recommendations.[3] The antibiotics used were ampicillin, aztreonam, erythromycin, cloxacillin, amoxicillin/clavulanic acid, amikacin, ceftazidime, cefotaxime, cefoperazone/sulbactam, cephalexin, cefoxitin, cefdinir, piperacillin/tazobactam, ceftriaxone, imipenem, meropenem, doripenem, ciprofloxacin, ofloxacin, gentamicin, doxycycline, netilmicin, co-trimoxazole, chloramphenicol, nitrofurantoin, fosfomycin, colistin, clindamycin, vancomycin, tigecycline, and linezolid. WHONET 5.6 was used for the analysis of antimicrobial resistance data.


  Results Top


A total of 656 patients were admitted to the ICU during the study period, out of which 277 patients had an ICU stay of less than 48 h. Of the total of 379 patients included in the study as per inclusion and exclusion criteria, 228 (60.2%) were males and 151 (39.8%) were females. Age distribution of patients admitted to the ICU is shown in [Figure 1]. One hundred and three patients (27.2%) developed at least one ICU-acquired infection. About 27.6% (63) of males and 26.5% (40) of females developed ICU-acquired infection. There were a total of 137 episodes of infections. VAP was the most common accounting for 60% (82) of all infections. CLABSIs accounted for 27% (37) and CAUTIs constituted 13% (18) of all ICU-acquired infections.
Figure 1: Age distribution of the study cohort

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[Table 1] shows the distribution of etiological agents of VAP, CLABSI, and CAUTI. A total of 82 bacterial isolates were identified in patients diagnosed with VAP. The most common bacteria isolated was P. aeruginosa (27%), followed by A. baumannii (22%). S. aureus caused 11% of cases of VAP. Other organisms identified in patients with VAP were Citrobacter spp. (17%), Klebsiella spp. (16%), Escherichia coli (3.5%), and Enterobacter spp. (3.5%).
Table 1: Etiological agents of VAP, CLABSI, and CAUTI

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The most common organisms causing CLABSI were P. aeruginosa and K. pneumonia, followed by A. baumannii, Citrobacter spp., S. aureus, A. calcoaceticus–baumannii complex (8.7%), and E. coli. CAUTI was most frequently caused by Enterococcus spp., Klebsiella spp., and Enterobacter spp. Other less frequent bacteria causing CAUTI were Citrobacter spp. and Serratia marcescens.

[Table 2] shows the antimicrobial susceptibility pattern of various Gram-negative microorganisms. The majority of the isolates of P. aeruginosa were resistant to amoxyclav, amikacin, doxycycline, cotrimoxazole, fluoroquinolones, third-generation cephalosporins, piperacillin/tazobactam, and tigecycline. Colistin (13.3% resistance) and carbapenem groups (16.6% resistance) were the most sensitive antibiotics for P. aeruginosa. For K. pneumoniae, colistin was the most effective antibiotic (16% resistance), followed by tigecycline (20% resistance) and meropenem (28% resistance). Acinetobacter showed the highest sensitivity to colistin (87.5% sensitivity), whereas it was observed to be highly resistant to all other antibiotics including fluoroquinolones (92–100% resistance), cephalosporins (87.5–96% resistance), piperacillin/tazobactam (92% resistance), carbapenems (71% for imipenem and 79% for meropenem and doripenem), and tigecycline (62.5%). Citrobacter and Enterobacter spp. showed a high degree of resistance to aztreonam, amikacin, fluoroquinolones, and cephalosporins, whereas colistin and tigecycline were the most effective antibiotics. All of the E. coli isolates were sensitive to doripenem, colistin, and tigecycline. The same has been depicted in [Figure 2].
Table 2: Antibiotic resistance pattern of Gram-negative microorganisms isolated from various ICU-acquired infections

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Figure 2: Antimicrobial resistance pattern of Gram-negative bacteria

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[Table 3] and [Figure 3] show the antibiotic resistance pattern of Gram-positive organisms. Approximately 71.4% isolates of S. aureus were MRSA with all strains sensitive to vancomycin and linezolid. A high degree of resistance was observed against beta-lactam antibiotics including cephalosporins, piperacillin/tazobactam, and carbapenems, fluoroquinolones, doxycycline, and clindamycin, whereas tigecycline was found to be effective (28.5% resistance). About 43% of the isolates of Enterococcus were VRE; however, all were sensitive to linezolid and tigecycline (0% resistance). About 71.5% of Enterococcus isolates showed sensitivity to carbapenems, whereas other antibiotics including cephalosporins, fluoroquinolones, doxycycline, and clindamycin were not effective with most of the isolates showing a high degree of resistance against them.
Table 3: Antibiotic resistance pattern of Gram-positive microorganisms isolated from various ICU-acquired infections

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Figure 3: Antimicrobial resistance pattern of Gram-positive bacteria

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  Discussion Top


ICUs worldwide are facing the crisis of continuing rise in multidrug-resistant bacteria, particularly those causing nosocomial infections. Among resistant bacteria, MRSA, VRE, third-generation cephalosporin-resistant Enterobacteriaceae, and imipenem-resistant P. aeruginosa and A. baumannii are of great concern because of their worldwide spread, which would have a significant impact on the treatment of infections caused by these organisms.

The precise pattern of causative pathogens usually varies between the ICUs, depending on several factors such as type of case (medical or surgical), antibiotic protocols, local ecology of microbes, and resistance patterns. Gram-negative organisms were predominant in causing nosocomial infections in the present study. We found that P. aeruginosa (22%), K. pneumonia (18.2%), and A. baumannii (17.5%) were the most common organisms associated with ICU-acquired infections, similar to the observations of Gupta et al.[4] and Joseph et al.[5] Several Indian studies have reported a high prevalence of P. aeruginosa, K. pneumonia, and A. baumannii in various ICU-acquired infections.[6],[7]

P. aeruginosa has also been implicated as the leading cause of nosocomial infections in the EPIC and other studies in accordance with the present study in which it was the most frequently isolated organism from the patients with VAP and CLABSI.[4],[5],[8]P. aeruginosa has numerous virulence factors, including many that appear to facilitate lung infection. The most important are a family of secreted exotoxins (ExoS, ExoT, ExoY) that are injected directly into the cytoplasm of host cells, using the so-called type III secretion system. A. baumannii is particularly important as a cause of outbreaks and can readily spread from one patient to another. This appears to be due to their ability to survive on healthcare workers’ hands and inanimate environmental surfaces and their intrinsic resistance to many common antibiotics rather than any potent virulence factor aimed at host defenses.

A very high degree of antimicrobial resistance was observed in the present study, particularly Gram-negative pathogens demonstrated multidrug resistance. P. aeruginosa is usually inherently resistant to many antimicrobial agents. This intrinsic resistance is mainly a result of the low permeability of the cell wall, production of inducible cephalosporinase, active efflux, and poor affinity for the target (DNA gyrase). In most ICU environments, this inherent resistance is further complicated by mutations mediated via chromosomes and the acquisition of resistant genes from plasmids and transposons. In the present study, members of the quinolones family exhibited a high resistance pattern, ciprofloxacin as the most resistant (92%) followed by ofloxacin (83.3%). Third-generation cephalosporins are known anti-pseudomonal drugs that have demonstrated a very high resistance pattern in the present study with P. aeruginosa isolates showing resistance of 93.3% for ceftazidime and 100% for cefoperazone/sulbactam. A high degree of resistance was also observed for piperacillin/tazobactam (60%) and tigecycline (66%). Colistin and carbapenems were reported to be the most sensitive antibiotics against P. aeruginosa in our study. Similar higher levels of resistance to piperacillin/tazobactam (91%) and ceftazidime (90%) among Pseudomonas were reported by Kumari et al.[9] An Indonesian study also showed a high rate of resistance to cephalexin (95.3%), cefotaxime (64.1%), and ceftriaxone (60.9%), whereas amikacin was the most effective antibiotic against P. aeruginosa followed by imipenem and meropenem.[10]

K. pneumoniae was also found to be multidrug-resistant to the quinolones and third-generation cephalosporins. It showed high rate of resistance to amikacin (64%), amoxiclav (100%), ceftazidime (88%), cefoperazone/sulbactam (92%), doxycycline (100%), ciprofloxacin (60%), ofloxacin (64%), and piperacillin/tazobactam (80%). Similar observations of a highly multidrug-resistant K. pneumoniae were also demonstrated by Radji et al.[10] and Goel et al.[11] Mahendra et al.[12] observed lower drug resistance of Klebsiella to amikacin (45%), piperacillin (55%), and ceftazidime (50%).

The growing development of multidrug resistance in Acinetobacter is an issue of significant concern. Resistance in Acinetobacter to the majority of antimicrobials raises an important therapeutic problem. The readily transferable antimicrobial resistance through resistance plasmids (R-plasmids) poses a major problem in Acinetobacter-associated nosocomial infections. We also depicted that a very high resistance pattern was expressed by A. baumannii. More than 85% of the isolates were resistant to third-generation cephalosporins and piperacillin/tazobactam, whereas 100% resistance was observed for several classes of antimicrobials including quinolones and aminoglycosides. We also reported a significant resistance to tigecycline (62.5%) and a very high prevalence of carbapenem resistance among Acinetobacter (71% imipenem and 79% meropenem and doripenem). Colistin was the most sensitive antibiotic for A. baumannii. In the same context, Lee et al.[13] showed that imipenem-resistant A. baumannii had much higher multidrug resistance (98.6%) and for those resistant isolates, only colistin and tigecycline were effective.

Among Gram-positive organisms, S. aureus and Enterococcus spp. were the most frequently isolated pathogens. S. aureus was implicated in 11% of VAP and 13.5% of CLABSI, and we observed a remarkably high incidence of MRSA (71.4%) whereas coagulase-negative staphylococci, which was the leading cause of CLABSI in the NNIS study and the studies by Parameswaran et al. and Salzman et al.,[14],[15],[16],[17] was not confirmed in our study. In the ICUs of seven Indian cities, MRSA was responsible for 87.5% of all infections caused by S. aureus.[18]Enterococcus spp. caused the maximum number of CAUTIs in our study. Laupland et al.[19],[20],[21] also reported Enterococcus spp. as the commonest pathogen causing CAUTI in their study. On the contrary, most studies on CAUTI have shown Gram-negative bacilli to predominate in the urine samples of infected patients.

The prescription of antibiotics in the ICUs is usually empiric and depends on the local ecology and resistance patterns. The present study highlights the significance of knowledge of local susceptibility and resistance patterns to guide the clinicians in making an informed decision while initiating the empiric antibiotics or organism-specific antimicrobial therapy. Appropriate and rational usage of antibiotics is imperative not only for favorable patient outcomes but also for thwarting the emergence of multidrug-resistant strains.

Ethical consideration

The Institutional Ethics Committee has approved the study protocol vide letter no. 27, dated November 18, 2016.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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