Abstract
Background
Resistance to antimicrobial agents is emerging in wide variety of nosocomial and community acquired pathogens. Widespread and often inappropriate use of broad spectrum antimicrobial agents is recognized as a significant contributing factor to the development and spread of bacterial resistance. This study was conducted to gain insight into the prevalent antimicrobial prescribing practices, and antimicrobial resistance pattern in nosocomial pathogens at a tertiary care hospital in Pune, India.
Methods
Series of one day cross sectional point prevalence surveys were carried out on four days between March and August 2014. All eligible in patients were included in the study. A structured data entry form was used to collect the data for each patient. Relevant samples were collected for microbiological examination from all the clinically identified hospital acquired infection cases.
Results
41.73% of the eligible patients (95% CI: 39.52–43.97) had been prescribed at least one antimicrobial during their stay in the hospital. Beta-lactams (38%) were the most prescribed antimicrobials, followed by Protein synthesis inhibitors (24%). Majority of the organisms isolated from Hospital acquired infection (HAI cases) were found to be resistant to the commonly used antimicrobials viz: Cefotaxime, Ceftriaxone, Amikacin, Gentamicin and Monobactams.
Conclusion
There is need to have regular antimicrobial susceptibility surveillance and dissemination of this information to the clinicians. In addition, emphasis on the rational use of antimicrobials, antimicrobial rotation and strict adherence to the standard treatment guidelines is very essential.
Keywords: Hospital acquired infection, Antibiotic sensitivity, Antifungal sensitivity, Microorganisms, Antimicrobial use
Introduction
Antimicrobial resistance (AMR) is a natural biological phenomenon and its emergence is a complex problem driven by many interconnected factors, in particular the use and misuse of antimicrobials. Resistance costs money, livelihoods and lives and threatens to undermine the effectiveness of health delivery programs.1 Resistance to antimicrobial agents is emerging in a wide variety of nosocomial and community acquired pathogens.2 Widespread and often inappropriate use of broad spectrum antimicrobial agents is recognized as a significant contributing factor to the development and spread of bacterial resistance.3 The Indian scenario too, is dismal with regard to antimicrobial prescribing and publications have documented the irrational prescribing patterns in various settings.4,5
Selective antimicrobial pressure is more in a hospital setting. Antimicrobials are prescribed in a community but not as intensively as in a hospital setting.6 As antimicrobial use generally precedes the emergence of antimicrobial resistance, preventing the emergence and spread of antimicrobial resistant pathogens clearly requires optimizing antimicrobial use.7
Hospitals need to monitor antimicrobial use in an attempt to reduce the emergence and spread of antimicrobial resistant pathogens.8 World Health Organization (WHO) highlights the establishment of effective, epidemiologically sound surveillance of antibiotic use and AMR among common pathogens in the community, hospitals and other health-care facilities as one of the key public health priorities.9 Limited literature is available regarding antimicrobial resistance in nosocomial pathogens from our country. The present study was conducted to gain insight into the prevalent antimicrobial prescribing practices; and antimicrobial resistance pattern, in hospital acquired infection organisms, at a tertiary care hospital in Pune, India.
Material and methods
A cross sectional study, comprised of four point prevalence surveys (PPS), was conducted during March–August, 2014 at a tertiary care hospital in Pune. PPS surveys were done to estimate (hospital acquired infection) HAI prevalence and antimicrobial usage among in-patients. The study subjects included all in-patients of the hospital at 08:00 h on the days of surveys. Patients admitted less than 48 h prior to the time of respective survey were excluded from the point prevalence survey.
Ethical approval was obtained from the institutional ethics committee. A written informed consent was obtained from each patient.
A structured data entry form was used to collect the data for each patient. It comprised of patient demographic data, consultant speciality, ward-wise location, diagnosis, antimicrobials used and presence of HAI risk factors. Generic name, days of use, route of administration and indication of use was recorded for each antimicrobial used in individual patients during their current stay in the hospital. HAI patients were identified on the basis of HAI definition as per CDC guidelines. All operational definitions as well as codes for various parameters were included in the questionnaire itself. A pilot study was conducted in two wards during December 2013, to validate the questionnaire, and the related customised database software.
Thirteen teams of surveyors were designated. Each team comprised of residents from Departments of Medicine, Surgery, Microbiology, Community medicine, Hospital administration; and Medical Officer in charge and Nursing Officer in charge of the respective wards. The teams had access to all relevant patients' medical documents, as well as the treating physicians/surgeons. Adequate pre-survey training was imparted to all the survey teams.
Four rounds of PPS for HAI and antimicrobial usage were done on 28 Mar, 06 May, 27 May and 08 Jul 2014 respectively.
Relevant samples as per the HAI type were collected for microbiological examination from all the identified HAI cases. Processing of samples was done as per standard microbiology protocols.10
We performed the Antibacterial Susceptibility Testing (ABST) by Vitek 2 compact (Biomerieux) automated system for identification and antimicrobial susceptibility testing of microorganisms.
The antifungal susceptibility testing was also performed using the same instrument using the fungal susceptibility cards.
Statistical methodology: The questionnaire of the PPS was thoroughly scrutinized and edited to ensure consistency of data in all the rounds. Statistical analyses were carried out using statistical software SPSS version 22.0.
Results
Study population
A total of 1886 patients were eligible for HAI surveys as per the inclusion criteria, during four rounds (R1–R4), as shown in Table 1.
Table 1.
Study population of patients.
| Round |
R1 |
R2 |
R3 |
R4 |
Total |
|---|---|---|---|---|---|
| Date | 28 Mar 14 | 06 May 14 | 27 May 14 | 08 Jul 14 | |
| Total | 501 | 553 | 558 | 507 | 2119 |
| Eligible | 461 | 491 | 490 | 444 | 1886 |
| HAI | 27 | 24 | 13 | 7 | 71 |
Demographics of the study population
Among the eligible patients, 77.3% were males and 22.7% were females. The median age of all patients was 35 years (Inter-quartile range (IQR) 26–51 years). The population pyramid displayed (Fig. 1) demonstrates the distribution of patients as per age and sex.
Fig. 1.
Demographics of the survey population.
HAI prevalence
71 patients among the eligible were detected to have an HAI clinically. Thus the overall prevalence of HAIs was 3.76% (95% CI = 2.97, 4.69). Out of them 32 had positive microbiology report.
Antimicrobial use
787 patients out of 1886 eligible patients, 41.73% (95% CI 39.52, 43.97) had been prescribed at least one antimicrobial during their stay in the hospital. A total of 1940 antimicrobials had been prescribed. These antimicrobials have been listed group-wise in Table 2.
Table 2.
Distribution of antimicrobial groups as per indication of use.
| Antimicrobial groups | Treatment of infection n (%) | Medical prophylaxis n (%) | Surgical prophylaxis n (%) | Total |
|---|---|---|---|---|
| Beta-Lactams (Penicillins & Cephalosporins) | 322 (43.5) | 60 (8.1) | 359 (48.4) | 741 |
| Protein Synthesis Inhibitors (Tetracyclines, Aminoglycosides Macrolides & Oxazolidones) | 210 (44.4) | 26 (5.5) | 237 (50.1) | 473 |
| Anti TB & Leprosy | 195 (100) | 0 (0) | 0 (0) | 195 |
| Antiprotozoal & Anti Helminths | 74 (44.6) | 40 (24.1) | 52 (31.3) | 166 |
| Fluoroquinolones | 90 (68.7) | 15 (11.5) | 26 (19.8) | 131 |
| Antivirals | 107 (97.3) | 2 (1.8) | 1 (0.9) | 110 |
| PABA Synthesis Inhibitors (sulphonamides) | 36 (62.1) | 20 (34.5) | 2 (3.4) | 58 |
| Antifungals | 38 (79.2) | 7 (14.6) | 3 (6.2) | 48 |
| Polypeptide antibiotics | 13 (92.9) | 0 (0) | 1 (7.1) | 14 |
| Antimalarial | 4 (100) | 0 (0) | 0 (0) | 4 |
Use of antimicrobial on a patient was classified on the basis of indication. More than half of the antimicrobials prescribed were for treatment of existing infections; followed by surgical prophylaxis as shown in Table 2.
Beta-lactams (38%) were the most prescribed antimicrobials, followed by Protein synthesis inhibitors (24%) as shown in Fig. 2.
Fig. 2.
Commonly prescribed antimicrobial groups.
Most commonly prescribed individual antimicrobials are classified as per WHO Anatomical, Therapeutic and Chemical (ATC) classification system as shown in Table 3 and shown in (Fig. 3). Preferred antimicrobials by different consultant specialties are shown in (Fig. 4).
Table 3.
Most commonly prescribed antimicrobials.
| Sr no | ATC codes | Antimicrobial | Total (%) |
|---|---|---|---|
| 1 | J01DD01 | Cefotaxime | 198 (10.20) |
| 2 | J01DD04 | Ceftriaxone | 172 (8.86) |
| 3 | J01GB06 | Amikacin | 154 (7.93) |
| 4 | J01XD01 | Metronidazole | 147 (7.57) |
| 5 | J01GB03 | Gentamicin | 130 (6.70) |
| 6 | J01CR02 | Amoxicillin + Clavulanic A | 99 (5.10) |
| 7 | J01DD12 | Cefoperazone | 79 (4.07) |
| 8 | J01MA12 | Levofloxacin | 69 (3.55) |
| 9 | J01XA01 | Vancomycin | 63 (3.24) |
| 10 | J01CR05 | Piperacillin + Tazobactam | 49 (2.52) |
| 11 | J01MA02 | Ciprofloxacin | 47 (2.42) |
| 12 | J01XA02 | Teicoplannin | 42 (2.16) |
| 13 | J01DH51 | Imipenem Cilastin | 37 (1.90) |
| 14 | J01DH02 | Meropenem | 35 (1.80) |
| 15 | J01EE01 | Cotrimoxazole | 31 (1.59) |
Fig. 3.
Most commonly prescribed antimicrobials.
Fig. 4.
Antimicrobial preference by consultant specialties.
30.36% of the patients with antimicrobial prescription were prescribed single antimicrobial, 31.76% with two, 21.09% with three and remaining 16.77% patients with four or more antimicrobials respectively.
Antibiotic Sensitivity Test (ABST) and antifungal sensitivity test of isolates
Majority of the organisms isolated from HAI cases were found to be resistant to the commonly used antimicrobials viz: Cefotaxime, Ceftriaxone, Amikacin, Gentamicin and Monobactams, but were sensitive to higher antimicrobials like Vancomycin, Teicoplanin, Colistin and Polymyxin B. It has been observed that even though antimicrobials like Chloramphenicol and Tetracycline are not being prescribed much these days, but many of the isolated organisms were found to be sensitive to them (Tables 4 and 5).
Table 4.
Antifungal sensitivity test of isolates.
Table 5.
ABST of isolates.
Discussion
The present study has found Point prevalence of HAI to be 3.76% (95% CI = 2.97, 4.69), which is lower than the rates reported by other hospitals in many developing countries. Recent systematic reviews have estimated hospital-wide prevalence of HAIs in high-income countries at 7.6% and in low and middle-income countries at 10.1%.11 This might be due to significant number of chronic patients being treated in hospital wards like psychiatry, dermatology and other lifestyle diseases.
In our study, prevalence of antimicrobial use (AMU) was found to be 41.73% (95% CI: 39.52–43.97). Similar study by the European Centre for Disease Prevention and Control (ECDC) reported AMU prevalence to be 34.6% (95% CI: 33.94–35.26).12
The most widely used antimicrobial group was beta-lactams (38%); 29.6% of which was intended for treatment, 35.29% for medical prophylaxis and 52.7% for surgical prophylaxis.
Ceftriaxone, Piperacillin + Tazobactum, Amikacin, AmoxiClav and Cefoperazone were among the most commonly prescribed antimicrobials by Medicine & Paediatrics specialties, even though most of the isolates were found to be resistant to them. Similarly Cefotaxime, Gentamicin, Amikacin and Metronidazole were the most commonly prescribed antimicrobials for surgical prophylaxis by specialties like Surgery, Obstetrics-Gynaecology and Orthopedics, but majority of the organisms isolated were found to be resistant to them.
ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species) pathogens were responsible for 24/38 (63.16%) of HAIs in our study. Nosocomial pathogens, such as Enterococcus faecalis and Acinetobacter species, are virtually untreatable due to multiple resistances. Similar results were obtained in some US hospitals.13,14 As seen in some other studies, microorganisms of HAI have more resistant profile than community acquired infection.15
Majority of the isolated organisms were found sensitive to Tetracyclines and Chloramphenicol, which are not routinely prescribed these days. Use of antimicrobials like Tetracyclines is advocated in community acquired infections to prevent emergence of resistance to other commonly used antimicrobials like Beta-lactam and Fluoroquinolones.
Several limitations need to be acknowledged for this study. It was conducted in a single hospital in a selected area. The small number of samples was examined microbiologically (Only samples collected from clinically detected HAI cases) and may affect the validity of conclusions drawn. The one time prevalence study nature may have influenced the prevalence rate and not depict the true rate as also the inability to determine the causality factors. However compared to time consuming and costly resource intensive incidence studies, repeated prevalence surveys are practical and efficient method of measuring trends over time. This methodology can be applied to any type of health-care institution including long-term care facilities.
Conclusion
There is a need to emphasize on the rational use of antimicrobials and strict adherence to the standard treatment guidelines. In addition, regular antimicrobial susceptibility surveillance and antimicrobial rotation is essential. The WHO Global Strategy defines the appropriate use of antimicrobials as the cost-effective use of antimicrobials which maximizes clinical therapeutic effect while minimizing both drug-related toxicity and the development of antimicrobial resistance.
Conflicts of interest
All authors have none to declare.
Acknowledgements
Declaration of AFMRC Project: This paper is based on Armed Forces Medical Research Committee Project No 4477/2013 granted by the office of the Directorate General Armed Forces Medical Services and Defence Research Development Organization, Government of India.
AFMC HAI STUDY GROUP
Department of Internal Medicine
Brig N Naithani, Brig Vasu Vardhan, Gp Capt S Shankar, Lt Col Aditya Gupta, Surg Lt Cdr Ramakant, Surg Lt Cdr P Chauhan, Surg Lt Cdr V A Arun, Maj R M Verghese, Maj Sambit Sundarey, Maj Khushboo, Maj Bhupesh Saini, Maj Anilkumar Abbot, Maj D K Jha, Dr Smriti Sinha, Dr Makarand Randive, Maj A V Pachisiya, Maj Arnab Choudhury, Maj S K Singh, Maj Dharmendra Singh, Dr BK Rashmi Yadav, Maj Arun Valsan and Lt Dr Tashi Dema
Department of Microbiology
Brig A K Sahni, Col Partha Roy, Col M Kumar, Col Naveen Grover, Maj D K Kalra, Maj Priyanka Pandit, Maj GS Bhalla, Maj Alina Singh, Dr Vaibhav Dudhat, Dr S Prasanna, Dr Nikunj Das, Dr Mungunthan M, Dr Santanu Hazra, Dr Anubha Patel and Dr Mayuri Kulkarni
Department of Community Medicine
Air Cmde A Mahen, Air Cmde S Mukherji, Surg Capt Dinesh Sharma, Mr D R Basannar, Dr Seema Patrikar, Maj Mona Dubey, Maj Gurpreet Singh, Maj Manoj Gupta, Maj Rekha Sharma, Maj Naveen Phuyal, Maj Lee Budhathoki, Dr Amol Nath, Dr Rohit Ambekar, Dr Sunil Diwate, Maj Shruti Vashisht, Maj Vikas Yadav, Maj Manjunath S R, Maj Vivek Phutane, Maj Neha Singh, Maj Kuntal Bandyopadhyay, Maj MS Brar, Dr Sabreen B, Dr Kailas Methe, Dr Swatej Hanspal, Dr Ayush Bhatnagar
Department of Hospital Administration
Brig A Chakravarty, Air Cmde RK Ranyal, VSM, Brig A Chatterjee, Lt Col Saurabh Ghosh, Maj Shashikant Sharma, Sqn Ldr Shailendra Singh, Maj Anupam Sahu, Capt Sunil Basukala, Dr Hrishikesh Pisal, Dr Vikas H, Dr Ashish Jain, Dr Swati Varshney and Dr Sania Shahbaz Hasnain
Department of Surgery
Air Cmde AK Pujahari, Col Vipon Kumar, Col S S Jaiswal, Surg Lt Cdr Imran Khan, Dr Dhinesh Kumar, Maj Murali Krishna KG, Maj Rajat Prabhakar, Maj Vasu Nikunj, Maj P K Sharma, Maj S P Tripathi, Maj Sivakumar, Maj J K Singh, Maj Manu Kumar Dhingra, Sqn Ldr Dheeraj Yadav, Maj Ankit Kumar, Maj Ajit Singh and Dr Satyaki Mukherjee
Department of Paediatrics
Surg Cmde Sheila S Mathai, VSM, Gp Capt SS Dalal, Lt Col Aparajita Gupta, Maj Kuldeep Mertiya, Maj Gaurav Kulshrestha and Dr I Lingamurthy
Department of Obstetrics and Gynaecology
Brig RD Wadhwa, VSM, Surg Capt Anupam Kapur, NM, Col A K Srivastava, Dr Vipin Kumar and Dr Vijayalakshmi
Department of Psychiatry
Lt Col Jyotiprakash, Lt Col A Saha and Maj Amitkumar
Department of Dermatology
Col Rajesh Verma, Lt Col Biju Vasudevan and Maj Veena Kharayat
Department of ENT
Sqn Ldr Anvita Bhansali
Department of Ophthalmology
Maj A Gupta
References
- 1.WHO global strategy . 2010. Containment of Antimicrobial Resistance. [Google Scholar]
- 2.Tenover F.C. Development and spread of bacterial resistance to antimicrobial agents: an overview. Clin Infect Dis. 2001;3(suppl 3):S108–S115. doi: 10.1086/321834. [DOI] [PubMed] [Google Scholar]
- 3.Tenover F.C., McGowan J.E., Jr. Reasons for the emergence of antimicrobial resistance. Am J Med Sci. 1996;311:9–16. doi: 10.1097/00000441-199601000-00003. [DOI] [PubMed] [Google Scholar]
- 4.Srishyla M.V., Nagarani N.A., Venkataraman B.V. Drug utilization of antimicrobials in the in-patient setting of a tertiary hospital. Indian J Pharmacol. 1994;26:282–287. [Google Scholar]
- 5.Das A.K., Roy K., Kundu K.K. Study of rational utilization and cost analysis of Antimicrobials in a government teaching hospital. Indian J Pharmacol. 2002;34:59–61. [Google Scholar]
- 6.Vander Stichele R.H., Elseviers M.M., Ferech M., Blot S., Goossens H. Hospital consumption of antibiotics in 15 European countries: results of the ESAC retrospective data collection (1997–2002) J Antimicrob Chemother. 2006;58:159–167. doi: 10.1093/jac/dkl147. [DOI] [PubMed] [Google Scholar]
- 7.Fridkin Scott K., Steward Christine D., Edwards Jonathan R. Surveillance of antimicrobial use and antimicrobial resistance in United States hospitals: project ICARE phase 2. Clin Infect Dis. 1999;29:245–252. doi: 10.1086/520193. [DOI] [PubMed] [Google Scholar]
- 8.Goldmann D.A., Weinstein R.A., Wenzel R.P. Strategies to prevent and control the emergence and spread of antimicrobial-resistant microorganisms in hospitals. JAMA. 1996;275:234–240. [PubMed] [Google Scholar]
- 9.WHO publication . 2012. The Evolving Threat of Antimicrobial Resistance: Options for Action. [Google Scholar]
- 10.Mackie and McCartney Practical Medical Microbiology. 14th ed. Churchill Livingstone; India: 2011. pp. 95–110. [Google Scholar]
- 11.Ogwang M., Paramatti D., Molteni T. Prevalence of hospital-associated infections can be decreased effectively in developing countries. J Hosp Infect. 2013;84:138–142. doi: 10.1016/j.jhin.2013.02.016. [DOI] [PubMed] [Google Scholar]
- 12.Zarb P., Coignard B., Griskeviciene J. The European Centre for Disease Prevention and Control (ECDC) pilot point prevalence survey of healthcare-associated infections and antimicrobial use. Euro Surveill. 2012;17:1–16. doi: 10.2807/ese.17.46.20316-en. [DOI] [PubMed] [Google Scholar]
- 13.Handwerger S., Raucher B., Altarac D. Nosocomial outbreak due to Enterococcus faecium highly resistant to vancomycin, penicillin, and gentamicin. Clin Infect Dis. 1993;16:750–755. doi: 10.1093/clind/16.6.750. [DOI] [PubMed] [Google Scholar]
- 14.Levin A.S.S., Mendez C.M.F., Sinto S.I. An outbreak of multiresistant Acinetobacter baumanii in a university hospital in São Paulo, Brazil. Infect Control Hosp Epidemiol. 1996;17:366–368. doi: 10.1086/647319. [DOI] [PubMed] [Google Scholar]
- 15.de Man P., Verhoeven B.A., Verbrugh H.A., Vos M.C., van den Anker J.N. An antibiotic policy to prevent emergence of resistant bacilli. Lancet. 2000;355:973–978. doi: 10.1016/s0140-6736(00)90015-1. [DOI] [PubMed] [Google Scholar]