|Ahead of print publication
Antimicrobial resistance surveillance among patients with sepsis in intensive care units of a tertiary care center
C Sanjeevan1, K Sandhya Bhat2
1 Intern, Pondicherry Institute of Medical Sciences, Puducherry, India
2 Professor of Microbiology, Pondicherry Institute of Medical Sciences, Puducherry, India
|Date of Submission||08-Apr-2022|
|Date of Decision||05-Jul-2022|
|Date of Acceptance||06-Jul-2022|
|Date of Web Publication||17-Sep-2022|
K Sandhya Bhat,
Professor, Department of Microbiology, Pondicherry Institute of Medical Sciences, Puducherry
Source of Support: None, Conflict of Interest: None
Background: Rising antimicrobial resistance (AMR) rate is a challenge for treating patients in health-care settings globally. Most intensive care unit (ICU) patients are frequently on antimicrobial agents; this induces selective antibiotic pressure and increases the threat of the development of AMR. The objective of this study was to document the microbiological profile and antimicrobial susceptibility pattern of the isolates from blood culture-confirmed cases of sepsis from ICUs at a tertiary care center.
Materials and Methods: A retrospective data collection was conducted after obtaining a waiver of consent from the institute ethics committee. A total of 151 patients, aged 18 years and above, admitted to the ICUs between January and December 2019 with blood culture-proven sepsis were included in the study. Data on demographic details, ICU stay, underlying risk factors, infecting organisms, and antimicrobial susceptibility reports were collected and analyzed using Microsoft Excel.
Results: A total of 1020 clinically suspected sepsis patients were admitted to the ICUs during the study period. Of these, 151 patients (14.8%) had blood culture-proven sepsis. Gram-negative bacteria were the most frequent isolates (63.6%), among which Escherichia coli was the most common pathogen (25%), followed by Klebsiella pneumoniae (15%), and Acinetobacter baumannii (13.6%). The rate of resistance was more against cephalosporins as compared to carbapenems and tigecycline. Commonly documented gram-positive bacterial isolates were coagulase-negative staphylococci (8.6%), viridans streptococci (7.1%), and Staphylococcus aureus (5%). About 65.2% of penicillin-resistance and 15.8% of methicillin-resistant staphylococci were documented.
Conclusion: This study on AMR was useful to know the prevalence of sepsis among ICU inpatients and the microbiological profile with their AMR pattern in our tertiary care hospital. This may help to generate local antibiograms which may further contribute to formulating the national data. Based on available antibiogram data, the choice of antibiotics for empiric treatment becomes easier. It may also guide the clinicians to escalate or de-escalate the antibiotics wherever possible.
Keywords: Antimicrobial resistance, empiric treatment, gram-negative bacteria, intensive care unit
|How to cite this URL:|
Sanjeevan C, Bhat K S. Antimicrobial resistance surveillance among patients with sepsis in intensive care units of a tertiary care center. J Curr Res Sci Med [Epub ahead of print] [cited 2022 Oct 6]. Available from: https://www.jcrsmed.org/preprintarticle.asp?id=356211
| Introduction|| |
Antimicrobial resistance (AMR) is in the rising trend and poses a huge burden to the health and economic status of the patients and health-care systems globally. About 0.7 million people die annually worldwide from multidrug-resistant (MDR) strains of microorganisms. The AMR burden is estimated to increase to 10 million by 2050. India has a large burden of infectious diseases, and being one of the largest consumers of antibiotics in the world, it is very important to rationalize the use of antibiotics for various infectious diseases.,
AMR surveillance is an important tool for assessing the burden of AMR and for providing the necessary antimicrobial susceptibility data, based on which the local, national, and global treatment guidelines can be planned., The global AMR surveillance system was launched by the World Health Organization (WHO) in 2015 to support a standardized approach for AMR data collection, analysis, and sharing at a global level., By the identification of various resistance patterns and the factors contributing to AMR, along with the reduced consumption of antimicrobial agents, may help in controlling the emergence and rapid spread of AMR among microbial pathogens.
Intensive care units (ICUs) worldwide are faced with the increasingly rapid emergence and spread of MDR bacteria. Both antibiotic-resistant gram-positive bacteria and gram-negative bacteria are being increasingly reported as important causes of healthcare-associated infections, especially in ICUs., The source of MDR bacteria may include repeated use of higher antibiotics, poor hand hygiene, lack of environmental cleaning, and reuse of materials used for individual patients.
The pattern of AMR varies widely from one country to another, as well as from one hospital to another and even among different ICUs within the same hospital. Knowledge about the microbial profile associated with sepsis and their susceptibility patterns will guide the selection of the empiric antimicrobial agents for these patients. Further, this may provide necessary information to formulate antibiotic policy to treat ICU patients with sepsis in tertiary care hospitals.
- To determine and document the proportion of blood culture-positive sepsis cases among clinically suspected cases of sepsis admitted in ICUs of a tertiary care hospital
- To determine and document the microbiological profile and antimicrobial susceptibility pattern of the isolates from blood culture-confirmed cases of sepsis from ICUs.
| Materials and Methods|| |
A descriptive retrospective study was conducted after obtaining a waiver of consent from the Institute Ethics Committee (IEC.No: RC/2021/28). Necessary permission was obtained from the hospital management for accessing patients' data in the Hospital Information Management System (HIMS). Retrospective data of all patients aged 18 years and above, admitted in various ICUs of a tertiary care center, and diagnosed with sepsis by positive blood culture from January 2019 to December 2019 were collected and analyzed. Repeat isolates from the same patients and if contaminants have grown in the blood cultures, those patients were excluded from the study.
The patients' demographic details, length of hospital stay, clinical details, associated risk factors, microbial pathogen/s isolated, and their antimicrobial susceptibility report were recorded from the laboratory work registers and HIMS.
All isolates from positive blood cultures were identified by their colony morphology and standard biochemical tests by conventional methods. The antimicrobial susceptibility testing was carried out and was interpreted as per the Clinical and Laboratory Standards Institute 2020 guidelines.
The antimicrobial agents tested by standard Kirby–Bauer disc diffusion technique for gram-negative bacterial isolates were cefazolin (30 μg), cefuroxime (30 μg), ciprofloxacin (5 μg), ceftriaxone (30 μg), cefotaxime (30 μg), ceftazidime (30 μg), cefepime (30 μg), gentamicin (10 μg), amikacin (30 μg), amoxicillin/clavulanate (20/10 μg), piperacillin/tazobactam (100/10 μg), cefoperazone/sulbactam (75/10 μg), imipenem (10 μg), meropenem (10 μg), and tigecycline (15 μg). Gram-negative bacterial isolates resistant to at least one agent in three or more classes of antimicrobials were recorded as MDR and were subjected to colistin microbroth dilution testing to determine the minimum inhibitory concentration (MIC).
The gram-positive bacterial isolates were subjected to disk diffusion testing against penicillin (10 units), cefotaxime (30 μg), erythromycin (15 μg), azithromycin (15 μg), clindamycin (2 μg), levofloxacin (5 μg), and linezolid (30 μg). High-level gentamicin (120 μg) and ampicillin (30 μg) was used for all Enterococcus isolates. Oxacillin screen agar and cefoxitin disk diffusion tests were used for screening for methicillin resistance and vancomycin screen agar for screening vancomycin resistance among Staphylococcus isolates. Oxacillin disc was used as a surrogate marker for determining penicillin resistance among Streptococcus pneumoniae isolates.
All Candida isolates from culture-proven sepsis cases were subjected to fluconazole and voriconazole disc diffusion testing.
Data entry was done using Microsoft Excel. Descriptive statistics such as frequencies, percentages, and mean ± standard deviation were used for analysis. The pattern of microorganisms was expressed as a percentage. Categorical variables were expressed as percentage susceptibility for each antimicrobial agent tested.
| Results|| |
Out of 1020 clinically suspected cases of sepsis aged 18 years or more, admitted in various ICUs of a tertiary care center, 166 (16.27%) patients were found to have positive blood cultures. Out of these, 10 (6.02%) patients' blood cultures grew contaminants, and 5 (3.01%) had repeat isolates; hence were excluded from further analysis. The remaining 151 patients (14.8%), with blood culture-positive sepsis cases, were included in the analysis. The mean age of the study group was 56.64 years (22–85 years). The male-to-female ratio was 2:1 (100 males and 51 females). Eighty-eight patients (58.3%), stayed for less than 10 days with a mean length of hospital stay of 8.87 ± 7.56 days.
Of the 151 patients from ICUs, the majority were clinically diagnosed to have sepsis and septic shock (n = 45, 29.8%), followed by 33 patients (21.9%) who had renal diseases. The clinical diagnosis of blood culture-positive sepsis patients is shown in [Table 1]. The majority of patients (n = 93, 61.5%) had type 2 diabetes mellitus as the major associated risk factor and 58 (38.4%) were catheterized during their ICU stay in the hospital.
Gram-negative bacteria were the major pathogens and were isolated from 96 patients (63.6%), while gram-positive bacteria were isolated from 44 patients (29.1%) and the remaining 11 patients (7.3%) had candidemia. Polymicrobial isolation was not documented in this study population. Escherichia coli was the most common pathogen (n = 35, 25%) isolated, followed by Klebsiella pneumoniae (n = 21, 15%) and Acinetobacter baumannii (n = 19, 13.6%). Among gram-positive bacterial isolates coagulase-negative staphylococci was most common (n = 12, 8.6%), followed by Streptococcus viridans (n = 10, 7.1%), and Staphylococcus aureus (n = 7, 5%). The spectrum of the bacterial isolates is shown in [Figure 1].
The Candida species that have been isolated include Candida tropicalis (6), Candida albicans (3), Candida parapsilosis (1), and Candida krusei (1).
Out of 96 gram-negative bacterial isolates AMR profile has been analyzed only for 87 isolates (E. coli [n = 35, 25%], K. pneumoniae [n = 21, 15%], A. baumannii [n = 19, 13.6%], P. aeruginosa [n = 6, 4.3%], [n = 9, 6.4%], Enterobacter species [n = 4, 2.9%] and Serratia marcescens [n = 2, 1.4%]). The resistance pattern of gram-negative bacterial isolates is shown in [Figure 2]. The remaining nine (nonfermenting gram-negative bacterial [n = 9, 6.4%]) isolates were excluded from further analysis, as their disc diffusion interpretation breakpoints are not available as per clinical and laboratory standards institute (CLSI); only MIC breakpoints are available.
|Figure 2: Antimicrobial agents tested for Gram-negative bacterial isolates and their resistance pattern|
Click here to view
AMR rate observed among 87 Gram-negative bacterial isolates was more against cephalosporins and less for carbapenems, and least for tigecycline shown in [Figure 2]. These isolates were further analyzed for MDR. Among these, 26 (17.3%) isolates were MDR, i.e. were resistant to at least one agent in three or more classes of antimicrobials tested. Of these majority were A. baumannii (n = 13, 50%), followed by E. coli (n = 7, 27%), K. pneumoniae (n = 4, 15.4%), and one each (3.8%) were Pseudomonas aeruginosa and Enterobacter species.
Among 44 gram-positive bacterial isolates, the overall AMR rate was 65.2% for penicillin, 17.9% for erythromycin, 15.4% for azithromycin, 15.2% for clindamycin, 13% for cefotaxime, and 12.5% for levofloxacin. Only one Enterococcus isolate was vancomycin-resistant, and no resistance was observed for linezolid among all 44 gram-positive bacterial isolates, as shown in [Figure 3].
|Figure 3: Antimicrobial agents tested for Gram-positive bacterial isolates and their resistance pattern|
Click here to view
About 60% of Enterococci isolates showed high-level gentamicin and ampicillin resistance. Out of 19 staphylococci isolates, five (15.8%) were cefoxitin resistant (two S. aureus and three coagulase-negative staphylococci); these isolates were documented as methicillin-resistant staphylococci
Out of 11 Candida isolates from the blood culture-proven sepsis cases, eight (Candida tropicalis  and Candida albicans ) were sensitive to both fluconazole and voriconazole. The remaining three yeast isolates (Candida albicans , Candida parapsilosis , and Candida krusei ) were found to be resistant to both fluconazole and voriconazole
| Discussion|| |
Despite many advances in diagnosis and treatment in the health-care settings, sepsis remains one of the leading causes of morbidity and mortality in developing countries. The etiological agents responsible for sepsis and their antimicrobial susceptibility profile are constantly changing., AMR is on the increasing trend, especially among patients admitted to ICUs for longer duration due to prolonged antibiotic pressure and multiple interventions. Continuous AMR surveillance has been recommended by the WHO as an essential step for controlling the emergence of resistance and rapid spread of resistance among microbes. Hence, this study was conducted to determine the microbiological profile and to document the antimicrobial susceptibility pattern of blood culture-proven sepsis isolates from clinically suspected cases of sepsis in ICUs.
In the present study, the proportion of blood culture-positive sepsis cases among clinically suspected cases of sepsis admitted in ICUs was 14.8%. Several studies have done elsewhere also reported a similar prevalence of blood culture positivity among sepsis patients admitted to ICUs.,, Majority of the patients were in the age group of 40–60 years (43.7%), with a male preponderance (male: female ratio was 2:1). Moolchandni et al and Nasir et al also observed a higher incidence of bacteremia among males. The difference may be due to variations in the patient population, such as medical ICUs or surgical ICUs. However, the reason for this difference is unclear and needs further analysis with a larger sample size.
In the present study, the majority of patients (29.8%) were clinically diagnosed to have sepsis and septic shock, followed by renal diseases (21.9%), and type 2 diabetes mellitus (61.5%) was the major underlying risk factor, followed by urinary catheterization (38.4%) during their hospital stay in ICUs. Sepsis and septic shock is one of the leading causes of ICU admission, followed by underlying renal conditions such as chronic kidney disease, respiratory failure, and gastrointestinal-related conditions. Uncontrolled diabetes mellitus and catheterization or any other instrumentation are the most common associated risk factors that can increase the chance of mortality among sepsis patients.,,
In the current study, gram-negative bacteria were more commonly isolated (63.6%) than gram-positive bacteria (29.1%) and followed by yeasts (7.3%). Similar observations were also documented in the study by Viderman et al. and Moolchandani et al.,, Among gram-negative bacteria, E. coli (25%), K. pneumoniae (15%), and A. baumannii (13.6%) were common isolates; whereas among gram-positive bacterial isolates, coagulase-negative staphylococci (8.6%), viridans streptococci (7.1%) and S. aureus (5%) were frequently isolated. There were 11 (7.3%) Candida isolates documented in this study, out of which three were resistant to both fluconazole and voriconazole. Similar observations were made by several other studies.,,
Among gram-negative bacterial isolates, an AMR rate of ≥40% was observed with 1st, 2nd, and 3rd generation cephalosporins. Resistance rate of 20 to <40% was observed with amoxicillin/clavulanate (35.5%), gentamicin (33.3%), cefoperazone/sulbactam (24.2%), piperacillin/tazobactam, and amikacin (20.7%) each. Less than 20% of the AMR rate was documented with meropenem (18.4%), imipenem (17.2%), and tigecycline (5.9%). A slightly high level of carbapenems resistance was observed in the study. About 17.3% of gram-negative bacterial isolates were MDR; of these majority were A. baumannii (50%), followed by E. coli (27%) and K. pneumoniae (15.4%). These isolates were mainly resistant to cephalosporins, ciprofloxacin, amoxicillin/clavulanate, gentamicin, and amikacin. Similar observations were also reported by several studies.,,,, However, all these isolates were intermediately susceptible to colistin. As per the latest CLSI guidelines, for colistin, only intermediate breakpoints are given. A combination of colistin with other antimicrobial agents is recommended rather than monotherapy for a better patient outcome .
The AMR among gram-positive bacterial isolates was observed highest with penicillin (65.2%), followed by erythromycin (17.9%), azithromycin (15.4%), and clindamycin (15.2%). About 15.8% methicillin-resistant staphylococci were documented and only one Enterococcus isolate was vancomycin-resistant; however, no resistance was observed for linezolid. Studies were done by many other researchers also documented the same susceptibility pattern for gram-positive bacterial isolates.,,,
This study was useful to know the prevalence of sepsis among patients admitted to ICUs and understand the associated risk factors, analyze the microbiological profile and their AMR pattern. With the increasing trend of worldwide AMR with limited treatment options available, regular antimicrobial surveillance is highly needed so that empirical antibiotics can be used wisely.
However, our study had a few limitations. As it was a retrospective study, no analysis could be done to distinguish between healthcare-associated and community-acquired infections. As there was a lack of detailed clinical profile analysis, differentiating the microbial isolates as a pathogen or colonizer could not be established. Especially for coagulase-negative staphylococci, Pseudomonas, Acinetobacter, and Candida isolation from blood among patients with prolonged ICU stay, it is difficult to distinguish unless regular follow-up of clinical condition and other associated risk factors are taken into account.
| Conclusion|| |
This study on AMR was useful to know the prevalence of sepsis among ICU inpatients and the microbiological profile of their AMR pattern in our tertiary care hospital. The increasing trend of MDR gram-negative bacilli (GNBs) to high-end antibiotics such as carbapenems and tigecycline is worrisome, as it leaves with limited antimicrobial treatment options like colistin. Similarly, the emergence of methicillin-resistant staphylococci and vancomycin resistant enterococci (VRE) pose a great challenge to health-care workers to manage other critically ill patients in the ICUs regarding isolation and infection prevention practices.
According to our study for clinically suspected sepsis patients, a combination of amikacin and carbapenem may be ideal for empiric treatment. In case of suspicion of gram-positive or yeast etiology, in addition, vancomycin and fluconazole can be added to the empiric treatment regimen. However, it is necessary to de-escalate according to the culture and antimicrobial susceptibility report for a better outcome and to reduce ICU stay. However, a study for longer periods with larger datasets would have given better representative data of susceptibility patterns for formulating antibiotic policy for sepsis in our hospital.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Kaur J, Dhama AS, Buttolia H, Kaur J, Walia K, Ohri V, et al.
ICMR's Antimicrobial Resistance Surveillance system (i
-AMRSS): A promising tool for global antimicrobial resistance surveillance. JAC Antimicrob Resist 2021;3:dlab023.
Walia K, Madhumathi J, Veeraraghavan B, Chakrabarti A, Kapil A, Ray P, et al.
Establishing antimicrobial resistance surveillance and research network in India: Journey so far. Indian J Med Res 2019;149:164-79.
] [Full text]
Moolchandani K, Sastry AS, Deepashree R, Sistla S, Harish BN, Mandal J. Antimicrobial resistance surveillance among Intensive Care Units of a tertiary care hospital in Southern India. J Clin Diagn Res 2017;11:DC01-7.
Gandra S, Alvarez-Uria G, Turner P, Joshi J, Limmathurotsakul D, van Doorn HR. Antimicrobial resistance surveillance in low- and middle-income countries: Progress and challenges in eight south Asian and Southeast Asian countries. Clin Microbiol Rev 2020;33:e00048-19.
Ghanshani R, Gupta R, Gupta BS, Kalra S, Khedar RS, Sood S. Epidemiological study of prevalence, determinants, and outcomes of infections in medical ICU at a tertiary care hospital in India. Lung India 2015;32:441-8.
] [Full text]
Kollef MH. Bench-to-bedside review: Antimicrobial utilization strategies aimed at preventing the emergence of bacterial resistance in the Intensive Care Unit. Crit Care 2005;9:459-64.
Chandi DH, Patil P, Bankar N, Damke S, Jain K. Antimicrobial resistance pattern of bacterial pathogens in Intensive Care Unit (ICU) of tertiary care hospital. Indian J Forensic Med Toxicol 2020;14:6396-401.
Annamallaei S, Bhat KS. Correlation of empiric antibiotic use with susceptibility pattern of blood isolates in septicemic patients in an Intensive Care Unit. J Curr Res Sci Med 2017;3:29. [Full text]
CLSI. Performance Standards for Antimicrobial Susceptibility Testing. CLSI Supplement M100. 30th
ed. USA: Clinical and Laboratory Standards Institute; 2020.
Muntean D, Horhat FG, Bădiăoiu L, Dumitraţcu V, Bagiu IC, Horhat DI, et al.
Multidrug-resistant gram-negative bacilli: A retrospective study of trends in a tertiary healthcare unit. Medicina (Kaunas) 2018;54:92.
CLSI. Method for Antifungal Disk Diffusion Susceptibility Testing of Yeasts; Approved Guideline. 2nd
ed., CLSI document M44-A2. Wayne PA: Clinical and Laboratory Standards Institute; 2009.
Nagarjuna D, Mittal G, Dhanda RS, Gaind R, Yadav M. Alarming levels of antimicrobial resistance among sepsis patients admitted to ICU in a tertiary care hospital in India – A case control retrospective study. Antimicrob Resist Infect Control 2018;7:150.
Javaid N, Sultana Q, Rasool K, Gandra S, Ahmad F, Chaudhary SU, et al.
Trends in antimicrobial resistance amongst pathogens isolated from blood and cerebrospinal fluid cultures in Pakistan (2011-2015): A retrospective cross-sectional study. PLoS One 2021;16:e0250226.
Previsdomini M, Gini M, Cerutti B, Dolina M, Perren A. Predictors of positive blood cultures in critically ill patients: A retrospective evaluation. Croat Med J 2012;53:30-9.
Mulatu HA, Bayisa T, Worku Y, Lazarus JJ, Woldeyes E, Bacha D, et al.
Prevalence and outcome of sepsis and septic shock in Intensive Care Units in Addis Ababa, Ethiopia: A prospective observational study. Afr J Emerg Med 2021;11:188-95.
Nasir N, Jamil B, Siddiqui S, Talat N, Khan FA, Hussain R. Mortality in Sepsis and its relationship with Gender. Pak J Med Sci 2015;31:1201-6.
Sutradhar M, Raj HJ, Trigunait P, Chhaule S, Ray R, Roy U, et al
. Antimicrobial resistance pattern of bacterial isolates among nosocomial infections (Urinary Tract Infection and Blood Stream Infection) from the Intensive Care Unit of a tertiary care government hospital in India. J Evol Med Dent Sci 2020;9:2284-8.
Viderman D, Khamzina Y, Kaligozhin Z, Khudaibergenova M, Zhumadilov A, Crape B, et al.
An observational case study of hospital associated infections in a critical care unit in Astana, Kazakhstan. Antimicrob Resist Infect Control 2018;7:57.
Savanur SS, Gururaj H. Study of antibiotic sensitivity and resistance pattern of bacterial isolates in Intensive Care Unit setup of a tertiary care hospital. Indian J Crit Care Med 2019;23:547-55.
Subramanya C. Clinical profile of patients with infection in Intensive Care Units in a tertiary care hospital. J Evolution Med Dent Sci 2021;10:268-72.
Negm EM, Mowafy S, Mohammed AA, Amer MG, Tawfik AE, Ibrahim AE, et al
. Antibiograms of Intensive Care Units at an Egyptian tertiary care hospital. Egypt J Bronchol 2021;15:1-5.
Pawar SK, Patil SR, Karande GS, Mohite ST, Pawar VS. Antimicrobial sensitivity pattern of clinical isolates in Intensive Care Unit in a tertiary care hospital from Western India. Int J Sci Study 2016;4:108-13.
Licata F, Quirino A, Pepe D, Matera G, Bianco A, Collaborative Group. Antimicrobial resistance in pathogens isolated from blood cultures: A two-year multicenter hospital surveillance study in Italy. Antibiotics (Basel) 2020;10:10.
[Figure 1], [Figure 2], [Figure 3]