|Year : 2017 | Volume
| Issue : 1 | Page : 29-35
Correlation of empiric antibiotic use with susceptibility pattern of blood isolates in septicemic patients in an Intensive Care Unit
S Annamallaei1, K Sandhya Bhat2
1 3rd Year MBBS Student, Pondicherry Institute of Medical Sciences, Puducherry, India
2 Department of Microbiology, Pondicherry Institute of Medical Sciences, Puducherry, India
|Date of Submission||25-Apr-2017|
|Date of Acceptance||13-May-2017|
|Date of Web Publication||12-Jul-2017|
K Sandhya Bhat
Department of Microbiology, Pondicherry Institute of Medical Sciences, Puducherry
Source of Support: None, Conflict of Interest: None
Background: Bloodstream infections remain a major cause of mortality and morbidity. Respiratory tract, genitourinary tract, and intra-abdominal foci are often the common identifiable foci of these infections. Definitive treatment based on blood cultures and susceptibility is essential to treat sepsis cases for better outcome. This study was conducted to document the bacteriological profile, their susceptibility pattern, antibiotics used for empiric and definitive treatment, escalation or de-escalation of antibiotics done following antibiogram report.
Materials and Methods: descriptive study was carried out for a period of 1 year after obtaining waiver of consent from Institute Ethics Committee. Demographic details, length of hospital stay, risk factors, bacteriological profile with antimicrobial resistance pattern, empiric antibiotic and definitive antibiotic given and outcome of patient were recorded. Statistical analysis was done by using IBM SPSS version 16.0 (SPSS Inc., Chicago, IL, USA) software.
Results: Overall prevalence of sepsis was 9.5%. Gram-negative bacteria were more commonly isolated (62.8%) than Gram-positive bacteria (37.2%), and Escherichia coli was the most common isolate (24.3%). Antimicrobial resistance among Gram-negative bacterial isolates was maximum with ciprofloxacin (51.3%) and ceftriaxone (45.2%), and least with amikacin, imipenem (16.7%), and polymyxin B (2.6%).
Penicillin group of antibiotics were commonly used for empiric treatment, and glycopeptides/polymyxins and carbapenems were most preferred for definitive treatment.
Conclusion: Knowledge about prevalence, risk factors, bacteriological profile, and their antibiogram resistance pattern is essential to select the antibiotic for the empiric treatment of suspected cases of sepsis and to formulate antibiotic policy. It is also important to de-escalate/escalate antibiotics according to the susceptibility report for a better outcome and to shorten the period of morbidity.
Keywords: Antibiogram, blood culture, blood stream infections, definitive treatment, empiric treatment
|How to cite this article:|
Annamallaei S, Bhat K S. 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;3:29-35
|How to cite this URL:|
Annamallaei S, Bhat K S. Correlation of empiric antibiotic use with susceptibility pattern of blood isolates in septicemic patients in an Intensive Care Unit. J Curr Res Sci Med [serial online] 2017 [cited 2022 Oct 4];3:29-35. Available from: https://www.jcrsmed.org/text.asp?2017/3/1/29/210337
| Introduction|| |
Bloodstream infections (BSIs) contribute a significant burden to public health, with mortality rate of 20%–50% worldwide and accounts for 10%–20% of all nosocomial infections., Respiratory tract, urogenital tract, and intra-abdominal foci are common identifiable nidus of BSIs. Isolation and identification of the pathogen by blood culture and antibiogram pattern of the isolate are vital steps in the diagnosis and management of the BSI.,
BSIs are in an upsurge, due to augmented use of indwelling medical devices, changing antimicrobial resistance pattern, and failure to follow infection control practices by the health care personnel. Inappropriate use of antibiotics has lead the Intensive Care Unit (ICU) to become a theater for selection of multidrug-resistant (MDR) microorganisms which in turn has led to a bothersome situation of nontreatable infections in ICUs., An early initiation of the appropriate antimicrobial treatment is crucial, and to select appropriate antibiotic for empirical therapy, clinician requires adequate knowledge about the etiological agents as well as their antibiogram pattern of prevalent microorganisms in that locality.,
This study was undertaken to document the common bacteriological profile and the most effective antimicrobial agent based on the susceptibility pattern of the isolates from cases of sepsis admitted in ICU and to document both empiric and definitive antimicrobial agent/s given for treatment, escalation, or de-escalation of antibiotics if any, following the antibiogram report, which would further help to determine whether appropriate antibiotics were used for these patients with sepsis.
- To detect the prevalence of blood culture positive sepsis cases among the patients admitted in ICU, in a tertiary care hospital
- To document the bacteriological profile and susceptibility pattern of all positive blood culture isolates
- To document antibiotics used for empiric treatment
- To correlate the susceptibility pattern of blood culture isolates with antibiotics given empirically and following the culture report.
| Materials and Methods|| |
A descriptive retrospective study was conducted after obtaining a waiver of consent from Institute Ethics Committee (RC. No: RC/16/02) and necessary permission from hospital management. Retrospective data of all patients admitted in ICU, in a tertiary care center, diagnosed with sepsis by positive blood culture during the period from June 2015 to May 2016, were collected and analyzed from hospital and laboratory records. Out of total of 129 patients with positive blood culture, only 78 patients had complete medical records and were included in the study. Repeat isolates from the same patients, and patients with incomplete case records were excluded from this study.
The demographic details, clinical details, length of hospital stay, associated risk factors, empiric antibiotic/s given, the outcome of each patient, along with bacteria isolated and its antibiogram report, antibiotic/s given for definitive treatment and any change in the antibiotic treatment or not following the final susceptibility report were recorded from laboratory work registers and hospital information system.
All the isolates were identified by colony morphology and standard biochemical tests by manual methods.
The antimicrobial agents tested by standard Kirby–Bauer disc diffusion technique were-amoxicillin + clavulanate (20/10 μg), piperacillin/tazobactam (100/10 μg), gentamicin (10 μg), amikacin (30 μg), cefotaxime (30 μg), ceftriaxone (30 μg), ceftazidime (30 μg), ceftazidime + clavulanate (30/10 μg), cefoperazone + sulbactam (75/10 μg), cefoxitin (30 μg), ciprofloxacin (5 μg), levofloxacin (5 μg), imipenem (10 μg), meropenem (10 μg), for all Gram-negative bacterial isolates and penicillin (10 units), amoxicillin + clavulanate (20/10 μg), erythromycin (15 μg), clindamycin (2 μg), ciprofloxacin (5 μg), amikacin (30 μg), co-trimoxazole (25 μg), for all Gram-positive isolates. High-level gentamicin (HLG [120 μg]) was used for all enterococci isolates and cefoxitin (30 μg), teicoplanin (30 μg), and linezolid (30 μg) were used on all staphylococci 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 Gram-positive bacterial isolates. The antimicrobial susceptibility reporting was recorded according to Clinical and Laboratory Standards Institute 2015 guidelines. All Gram-negative bacterial isolates (49 isolates) were also analyzed whether they were MDR or not according to standard guidelines.
Data entry was done using Microsoft Excel and analysis was done using SPSS for Windows Version SPSS version 16.0 (SPSS Inc., Chicago, IL, USA). Mean and standard deviations were calculated for numerical variables. Percentages were calculated for categorical variables. Data were analyzed using Chi-square test. P < 0.0001 was considered significant.
| Results|| |
Out of 1350 clinically suspected patients with sepsis admitted in ICU in the study period, 129 (9.5%) were blood culture positive. Out of these, only 78 (60.4%) patients were included for the study. Maximum patients (35 [44.9%]) were ≥60 years, with the mean age of the study population was 57.15 ± 16.715 years, with 65.4% males. Male to female ratio was 1.9:1. The majority of patients (61.5%), stayed in the hospital for <10 days, with mean length of hospital stay was 9.77 ± 5.470 days. In our study, 44 (56.4%) showed clinical improvement at the time of discharge, death was recorded in 11 (14.1%) patients, and 23 (29.5%) patients were discharged against medical advice.
Type 2 diabetes mellitus was the major associated risk factor (50 [64.1%]), followed by hypertension 35 (44.9%) and 47 (60.3%) were catheterized during their stay in the ICU. Among them, majority (21.8%) were clinically diagnosed to have sepsis and septic shock, followed by 20.5% had renal diseases, 15.4% had central nervous system (CNS) diseases, 14.1% had respiratory tract diseases, 11.5% had gastrointestinal diseases, 10.3% had diabetic associated complications, 3.8% had Cardiovascular diseases, and 2.6% had postoperative infections.
Among the study group, Gram-negative bacteria were isolated from 49 (62.8%) cases and Gram-positive bacteria from 29 cases (37.2%). Polymicrobial isolation was recorded from two cases; one case with Escherichia More Details coli and Klebsiella pneumoniae and another with Pseudomonas aeruginosa and K. pneumoniae (1.3% each). Distribution of the bacteriological profile among patients with blood culture positive sepsis is shown in [Figure 1].
|Figure 1: Distribution of the bacteriological profile among patients with blood culture positive sepsis|
Click here to view
The overall antimicrobial resistance rate observed among 49 gram negative bacterial isolates in the decreasing order was as follows: ciprofloxacin (51.3%), ceftriaxone (45.2%), ceftazidime (45.2%), amoxicillin + clavulanate (43.6%), cefotaxime (43.6%), meropenem (29.5%), cefoperazone + sulbactam (24.4%), piperacillin + tazobactam (23.1%), gentamicin (23.1%), amikacin (16.7%), imipenem (16.7%), and polymyxin B (2.6%) as shown in [Figure 2]. Among these, 38 (77.6%) isolates were MDR, and their distribution is shown in [Figure 3].
|Figure 2: Antimicrobial agents tested for Gram-negative bacterial isolates and their resistance pattern|
Click here to view
|Figure 3: Multidrug-resistant Gram-negative isolates from blood culture positive sepsis cases|
Click here to view
Among 29 gram positive bacterial isolates, the overall antimicrobial resistance rate in the decreasing order was as follows: ciprofloxacin (54.5%), ampicillin (50%), cefotaxime (44.4%), cephazolin (41.6%), azithromycin (37.5%), penicillin (30%), erythromycin and gentamicin (16.7%) and amikacin (12.5%) and no resistance was observed to levofloxacin, clindamycin, vancomycin, teicoplanin, and linezolid as shown in [Figure 4]. HLG resistance recorded among enterococci isolate was 50%. Out of 14 staphylococci isolates tested, 42.8% showed resistance to cefoxitin, i.e., these isolates were reported as methicillin-resistant staphylococci.
|Figure 4: Antimicrobial agents tested for Gram-positive bacterial isolates and their resistance pattern|
Click here to view
In the present study, usage of antimicrobial agents for empiric treatment was as follows: ≥1 antibiotics used (35.9%), penicillin group of antibiotics (23.1%), cephalosporin group (23.1%), carbapenems, fluoroquinolones, glycopeptides/polymyxins, and macrolides (2.6%) each, and aminoglycosides (1.3%), as shown in [Figure 5]. Antibiotics used for definitive treatment following susceptibility report is shown in [Figure 6].
|Figure 5: Antimicrobial agents used for empiric treatment among patients with blood culture positive sepsis|
Click here to view
|Figure 6: Antimicrobial agents used for definitive treatment among patients with blood culture positive sepsis|
Click here to view
In the current study, penicillin group and cephalosporin group of antibiotics were commonly used for empiric treatment (29.5% and 23.1%, respectively) and 28 patients (35.9%) continued to receive the empiric treatment and 50 patients (64.1%) received a different class of antibiotic following the antimicrobial susceptibility report. Change of antibiotics used for definitive treatment as compared to empiric treatment among these patients is shown in [Table 1].
|Table 1: Change of antibiotics used for definitive treatment as compared to empiric treatment among patients with blood culture positive sepsis|
Click here to view
Among patients who continued to receive the same empiric antibiotic, following the blood culture susceptibility report, 72.7% improved; whereas 27.3% died and among those who received a different class of antibiotic for definitive treatment, 87.8% of them showed clinical improvement at the time of discharge, and 12.2% died [Figure 7]. However, we did not observe any statistical significance between the two groups, as P = 0.41 (by Chi-square test).
|Figure 7: Outcome of patients by empiric and definitive antibiotic therapy|
Click here to view
| Discussion|| |
Despite advances in diagnosis and treatment in the medical care, bacterial sepsis remains as one of the leading cause of morbidity and mortality, particularly among neonates and elderly patients in developing countries. The etiological agents causing sepsis and their antimicrobial susceptibility are constantly evolving. Hence, the study of bacteriological profile with antibiotic susceptibility pattern plays an important role in effective management of BSI cases.
In the current study, overall prevalence of sepsis was 9.5%, i.e., 129 patients were blood culture positive sepsis cases out of 1350 clinically suspected cases of sepsis. Out of these, only 78 (60.4%) patients were included for the study and further data analysis. Several studies done elsewhere also reported the similar prevalence of blood culture positive sepsis cases (8.39%, 9.2%),, etc. However, several other studies reported higher rates of blood culture positive sepsis cases (25%–43.78%), probably as these studies were done among pediatric patients; bacteremia is more common in neonates and children of <10 years., Most of the patients (44.9%) were in the age group of >60 years, with a male preponderance. Joshi et al., and Tiwari, also observed a higher incidence of bacteremia among males. The reason for this difference is unclear and need further study with large sample size.
In the present study, mean length of hospital stay of the study population was 9.77 ± 5.470 days. The majority of patients, i.e., 9/13 (69.2%) who showed improvement at the time of discharge were in the age group of 18–40 years; however, death was observed maximum, i.e., 6/35 (17.1%) patients over >60 years as compared to <60 years. Observations made by several studies have found old age, and prolonged hospital stay is important risk factors for predisposition to severe sepsis., Associated morbid conditions such as diabetes mellitus, hypertension, and underlying renal conditions probably were the reasons for prolonged hospitalization and increased mortality observed in these patients over 60 years. The majority of the patients (64.1%) were type 2 diabetics, and 60.3% were catheterized during their stay in the ICU; these observations were consistent with the study done by Lueangarun and Leelarasamee and Bijou et al., where uncontrolled diabetes mellitus and prolonged urinary catheterization were more commonly associated with sepsis.,
In the current study, majority of patients (21.8%) were clinically diagnosed to have sepsis and septic shock, followed by renal diseases (20.5%), CNS diseases (15.4%), respiratory tract diseases (14.1%), gastrointestinal diseases (11.5%), diabetic-associated complications (10.3%), CVS diseases (3.8%), and 2.6% had postoperative infections. Mehta et al., and Jarvis et al have also made the similar observations in their studies done elsewhere.,
In the current study, Gram-negative bacteria were more commonly isolated (62.8%) than Gram-positive bacteria (37.2%). Similar observations were also done in the study by Gupta and Kashyap, and Rajeevan et al., Polymicrobial isolation was recorded from two cases (2.6%). Polymicrobial infection reported by various studies is 4.7%–18.7%, most of which were hospital acquired.
Antimicrobial resistance rate among all Gram-negative bacterial isolates was observed highest with ciprofloxacin (51.3%), followed by ceftriaxone and ceftazidime (45.2%), and least with imipenem (16.7%) and polymyxin B (2.6%). The two cases (2.6%) of polymyxin B resistance was observed by Burkholderia pseudomallei, which are intrinsically resistant to it. Hence, no strain isolated showed acquired resistance to polymyxin B. Similar resistance patterns were also observed by several other studies.,,,
MDR observed among the Gram-negative isolates was 77.6%; of which, 47.36% isolates were E. coli, followed by 26.31% K. pneumoniae. These MDR bacterial isolates mainly were resistant to ampicillin, ciprofloxacin, gentamicin, cefotaxime/ceftriaxone, and meropenem. Similar observations are also reported by several studies.,,,,
Antimicrobial resistance rate among all Gram-positive bacterial isolates was observed highest with ciprofloxacin (54.5%); followed by ampicillin (50%) and all the isolates were uniformly susceptible to clindamycin, levofloxacin, vancomycin, teicoplanin, and linezolid. Studies done by many other researchers also observed same susceptibility pattern for Gram-positive bacterial isolates.,,,
Penicillin group of antibiotics were used highest (29.5%) for empiric treatment among all blood culture positive sepsis cases, followed by cephalosporin group (23.1%), and in 35.9% patients, more than one antimicrobial agents were used. Glycopeptides/polymyxins group of antimicrobials were used highest (15.4%) for definitive treatment among all blood culture positive sepsis isolates, followed by cephalosporins and carbapenems (12.8%), and in 44.9% patients, more than one antimicrobial agents were used for definitive treatment. In the current study, 35.9% of patients continued to receive the empiric treatment and 64.1% patients received a different class of antibiotic for definitive treatment following the antimicrobial susceptibility report. About 72.7% of patients continued to receive the same empiric antibiotic, following susceptibility report and improved; whereas 27.3% died and among those who received a different antibiotic for definitive treatment, 87.8% of them showed clinical improvement at the time discharge and 12.2% died. A study done by Lueangarun and Leelarasamee showed two important factors responsible for adverse events and death in septic patients were the initiation of inappropriate empiric antimicrobial therapy and the delay of definitive antimicrobial therapy. However, we did not observe any statistical significance between the two groups.
This study was useful as it helped to know the prevalence of sepsis, understand risk factors responsible for sepsis, analyze bacteriological profile and their antibiogram resistance pattern.
This would be helpful in starting empiric treatment as well to formulate an antibiotic policy for treatment of cases with sepsis. However, as it was a retrospective study, due to unavailability of data, we had to exclude large amount of patients (39.6%); hence, larger sample size would have helped us to get conclusive evidence on the impact of definitive therapy on outcome of patients with sepsis. It is also important to de-escalate according to the antimicrobial susceptibility report for a better outcome and to shorten the period of morbidity. Greater number of bacterial isolates would have given a better representative data of antibiogram for formulating antibiotic policy and empiric treatment of sepsis in our hospital.
| Conclusion|| |
Considering the high mortality rate of severe sepsis and difficulties in predicting its course, it is very important to prevent the illness from occurring by identifying the underlying cause and appropriate early treatment of BSIs. Early recognition of symptoms followed by appropriate microbiological and radiological investigations to aid in diagnosis is essential to improve the patient outcome. As per our study, combination of amikacin and imipenem for empiric treatment is ideal for suspected patients with Gram-negative bacterial sepsis. Future prospective study on large sample size would be helpful in deriving at a clear conclusion regarding the development of antibiotic policy among these patients with sepsis.
Dr Sudhagar M., Associate Professor, Department of Medicine, Pondicherry Institute of Medical Sciences.
Financial support and sponsorship
This project was supported and funded by PIMS fellowship 2016.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gupta S, Kashyap B. Bacteriological profile and antibiogram of blood culture isolates from a tertiary care hospital of North India. Trop J Med Res 2016;19:94. [Full text]
Saeed M, Rasheed DF, Ashraf PD, Iram DS, Hussain S, Khawaja DA. Pathogens causing blood stream infections; in cardiac patients & their susceptibility pattern from a tertiary care hospital. Prof Med J 2015;22:1617-23.
Mehta M, Dutta P, Gupta V. Antimicrobial susceptibility pattern of blood isolates from a teaching hospital in north India. Jpn J Infect Dis 2005;58:174-6.
Pandey S, Raza S, Bhatta CP. The aetiology of the bloodstream infections in the patients who presented to a tertiary care teaching hospital in Kathmandu, Nepal. J Clin Diagn Res 2013;7:638-41.
Bhatta DR, Gaur A, Supram HS. Bacteriological profile of blood stream infections among febrile patients attending a tertiary care centre of Western Nepal. Asian J Med Sci 2013;4:92-8.
Garg A, Anupurba S, Garg S, Goyal RK, Sen MR. Bacteriological profile and antimicrobial resistance of blood culture isolates from a university hospital. JIACM 2007;8:139-43.
Mackie TJ, McCartney JE. Practical Medical Microbiology. 14th
ed., Ch. 21. New York: Churchill Livingstone; 1996. p. 385-402.
Clinical Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. Twenty-Second Informational Supplement. CLSI Document M100-S22. Ed. 26th
, Wayne, PA: CLSI; 2016.
Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al.
Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012;18:268-81.
Negussie A, Mulugeta G, Bedru A, Ali I, Shimeles D, Lema T, et al.
Bacteriological profile and antimicrobial susceptibility pattern of blood culture isolates among septicemia suspected children in selected hospitals Addis Ababa, Ethiopia. Int J Biol Med Res 2015;6:4709-17.
Rani VN, Gopal K, Narendra VM, Vishwakanth D, Nagesh VR, Yogitha M, et al
. A retrospective study on blood stream infections and antibiotic susceptibility patterns in a tertiary care teaching hospital. Int J Pharm Pharm Sci 2012;4:543-8.
Gohel K, Jojera A, Soni S, Gang S, Sabnis R, Desai M. Bacteriological profile and drug resistance patterns of blood culture isolates in a tertiary care nephrourology teaching institute. Biomed Res Int 2014;2014:153747.
Prabhu K, Bhat S, Rao S. Bacteriologic profile and antibiogram of blood culture isolates in a Pediatric Care Unit. J Lab Physicians 2010;2:85-8.
] [Full text]
Tiwari DK. A study on the bacteriological profile and antibiogram of bacteremia in children below 10 years in a tertiary care hospital in Bangalore, India. J Clin Diagn Res 2013;7:2732-5.
Joshi SG, Ghole VS, Niphadkar KB. Neonatal gram-negative bacteremia. Indian J Pediatr 2000;67:27-32.
Nasa P, Juneja D, Singh O. Severe sepsis and septic shock in the elderly: An overview. World J Crit Care Med 2012;1:23-30.
Martin GS, Mannino DM, Moss M. The effect of age on the development and outcome of adult sepsis. Crit Care Med 2006;34:15-21.
Lueangarun S, Leelarasamee A. Impact of inappropriate empiric antimicrobial therapy on mortality of septic patients with bacteremia: A retrospective study. Interdiscip Perspect Infect Dis 2012;2012:765205.
Bijou MR, Bhat KS, Kanungo R. Characteristics of blood stream isolates in urosepsis from a tertiary care hospital. Int J Curr Microbiol Appl Sci 2016;5:424-31.
Jarvis WR. The evolving world of healthcare-associated bloodstream infection surveillance and prevention: Is your system as good as you think? Infect Control Hosp Epidemiol 2002;23:236-8.
Rajeevan S, Ahmad SM, Jasmin PT. Study of prevalence and antimicrobial susceptibility pattern in blood isolates from a tertiary care hospital in North Kerala, India. Int J Curr Microbiol Appl Sci 2014;3:655-62.
Lockhart SR, Abramson MA, Beekmann SE, Gallagher G, Riedel S, Diekema DJ, et al.
Antimicrobial resistance among Gram-negative bacilli causing infections in Intensive Care Unit patients in the United States between 1993 and 2004. J Clin Microbiol 2007;45:3352-9.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]