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 ~  Abstract
 ~  Material and Methods
 ~  Results
 ~  Discussion
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Year : 2004  |  Volume : 22  |  Issue : 2  |  Page : 115-118

Application of whonet for the surveillance of antimicrobial resistance

Department of Microbiology, Indira Gandhi Medical College, Shimla - 171 001, Himachal Pradesh, India

Correspondence Address:
Department of Microbiology, Indira Gandhi Medical College, Shimla - 171 001, Himachal Pradesh, India

 ~ Abstract 

World over antimicrobial resistance is a major public health problem. The WHONET software program puts each laboratory data into a common code and file format, which can be merged for national or global collaboration of antimicrobial resistance surveillance. In this study, antimicrobial sensitivity of 4,289 bacterial isolates was studied by Kirby-Bauer disk diffusion method. -lactamase production was assessed by iodometric test method. Extended spectrum -lactamase (ESBLs) were screened by ceftazidime disk sensitivity. Drug resistance was high in most of the isolates. It was maximum (80-94%) for ampicillin, nalidixic acid and cotrimoxazole. It varied between 40-60% for gentamicin, clindamycin, fluoroquinolones and coamoxyclav. It ranged from 21 to 38% for amikacin and third generation cephalosporins. Constitutive -lactamase production was highest in S.aureus (28.9%) and ESBL production was maximum in Klebsiella spp. (53.6%). WHONET software has in-built analysis program which helps in forming hospital drug policy, identification of hospital outbreaks and recognition of quality control problems in the laboratory.

How to cite this article:
Sharma A, Grover P S. Application of whonet for the surveillance of antimicrobial resistance. Indian J Med Microbiol 2004;22:115-8

How to cite this URL:
Sharma A, Grover P S. Application of whonet for the surveillance of antimicrobial resistance. Indian J Med Microbiol [serial online] 2004 [cited 2020 Nov 24];22:115-8. Available from:

The emergence and dissemination of resistant bacteria is a natural process in which bacteria get adapted to a hostile environment rich in antibacterial agents. However, it is not a phenomenon, which we cannot influence. This is evident from the fact that there is tremendous difference in the prevalence of resistance in hospitals and communities throughout the world .The advent of penicillin in 1944 suggested the defeat of infection. Within a few years, resistant Staphylococcus aureus burst the euphoric bubble. b lactam antimicrobial agents are still most widely used and so is the resistance against them. The most important mechanism of resistance to b lactam agents is the production of the enzyme b-lactamase which destroys the b lactam ring. They are produced constitutively or as induced enzymes.[1] It was believed that cephalosporins are relatively immune to b-lactamases. It was disappointing when in Klebsiella spp. plasmid mediated resistance was found against broad-spectrum cephalosporins. The resistance was attributed to novel b-lactamase enzymes known as extended spectrum beta lactamases (ESBLs).[2] The World Health Organization has established a program to tackle the problem of antimicrobial resistance. It is known as Antimicrobial Resistance Monitoring (ARM) program. It requires accurate and easily accessible data on antimicrobial resistance to support decision making and to take action from local to the global level. To achieve all this, WHO has devised an electronic format and named it WHONET.[1]
Realizing the high prevalence of drug resistance in bacterial population, present study was carried out with the aim of surveillance of drug resistance and to detect b-lactamase production in various bacterial isolates. This data was analysed with the help of WHONET4 software.

 ~ Material and Methods Top

The present study was conducted in the Department of Microbiology, IGMC, Shimla from July 1999 to June 2000. All the clinical samples received in the department for culture and sensitivity for aerobic bacteria were subjected to this study. Isolation of pathogenic bacteria from clinical specimens and identification to the species level was performed by standard methods.[3] The antimicrobial sensitivity testing was done by Kirby-Bauer disc diffusion method standardized as per NCCLS.[1] Antibiotics were selected according to WHO model list of essential drugs.[1] For internal quality control  E.coli   (ATCC 25922), S.aureus (ATCC 25923) and P.aeruginosa (ATCC 27853) strains were used.[1] E.coli  b-lactamase production was assessed by iodometric test method.[3] ESBLs were screened by ceftazidime discs. NCCLS breakpoints for third generation cephalosporins have recently been revised to more sensitively detect ESBL production. Since most ESBLs inactivate ceftazidime it was used for screening all the isolates.[1] Main prerequisite for compilation of data was a PC installed with WHONET software. All data was entered into the program manually on a daily basis. A large number of permutation combinations were available in the program for analysis. Software was obtained from WHO seminar on a floppy.

 ~ Results Top

During one year period 21,886 samples were received for culture and sensitivity of aerobic bacteria. From these samples a total of 4,289 bacterial isolates were obtained. All the isolates were studied for sensitivity pattern against various antibiotics and b-lactamase production. The various specimens comprised of urine (39%), pus (37%), blood (8.6%), stool (5.8%) and others (9.6%). During the study period 25 different species of bacteria were isolated. E.coli comprised the maximum number of isolates i.e. 41.9% followed by S.aureus 25.2%. The others comparatively in high number were Klebsiella spp. (9%) and P.aeruginosa (7.1%). Sensitivity pattern of all the isolates is shown in the [table]. The resistance rates varied from as low as 20.7% for cefaperazone to as high as 94% for ampicillin. A total of 20.8% isolates were producers of b-lactamases as found by iodometric test method. On the other hand, screening for the production of ESBL with ceftazidime disc showed that 38.5% of the isolates were the producers of ESBLs. The figure shows comparison of constitutive and ESBL production.

 ~ Discussion Top

Surveillance of resistance is essential to monitor and control the spread of antimicrobial resistance. Susceptibility test results of tens of thousands of laboratories around the world are stored in paper files or in computer files, which makes them inaccessible for analysis and comparison. The WHONET program provides uniform guidelines for performing antimicrobial susceptibility tests. It also provides a software through which data from each laboratory is entered into a common code and file format for that laboratory.[1] This data can be shared with another laboratory working on WHONET program for further collaboration and for implementation of various control measures. The WHONET software was originally devised by the WHO collaborating center for surveillance of antibiotic resistance, Boston, MA, USA and further developed by WHO in Geneva. WHONET is distributed free of cost by WHO.[4]
The articles published so far on the basis of WHONET software are limited. One study was conducted in 11 hospitals of Beijing in 1995.[5] A National Electronic Network was launched in Greece on earlier version of WHONET software[4] and the study was conducted in 19 hospitals of Greece. Their experience of four years helped them in identifying main factors responsible for the emergence of antimicrobial resistance. It also helped in identifying the sub-population of resistant bacteria for molecular studies and facilitated the formation of hospital based empirical therapy. Manninen et al recommend use of WHONET software to get laboratory specific breakpoints to avoid false reporting of resistance.[6]
The present study shows that highest resistance was against ampicillin (94%) followed by nalidixic acid and cotrimoxazole (86.4 and 80.8%, respectively). Resistance rate to majority of drugs was 42-59%. These include clindamycin, erythromycin, netilmicin, gentamicin, ciprofloxacin, norfloxacin, piperacillin, nitrofurantoin, amikacin and coamoxyclav. Resistance to ceftazidime and cefaperazone was 38.5 and 20.7%, respectively. Nema et al found that 73-99% of gram negative isolates were resistant to common antibiotics like ampicillin, chloramphenicol, cotrimoxazole and first generation cephalosporins. The resistance to gentamicin and ciprofloxacin ranged from 53 to 79%. Resistance to amikacin, netilmicin and third generation cephalosporins (3GC) ranged from 30 to 73%.[7] Rossi et al found that more than 50% urinary isolates of E.coli were resistant to ampicillin and more than 30% to cotrimoxazole.[8] Valdivieso et al conducted a twelve month study in 11 Chilean hospitals on urinary isolates.[9] They found that 65% strains of E.coli were resistant to ampicillin, 43% to cotrimoxazole, 9% to ceftazidime, 4.2% to gentamicin, 5.6% to ciprofloxacin, 4.3% to nitrofurantoin and 1.3% to amikacin.
b-lactamases production is a very important cause of antimicrobial resistance in bacteria. In the present study, the most common organism producing constitutive b-lactamase was S.aureus (28.9%) followed by Proteus spp. (24.5%), whereas Klebsiella spp. (53.6%) showed highest percentage of ESBL production followed by Proteus spp. (51.1%). Jones et al found 23.8% isolates of Klebsiella spp. to be resistant to ceftazidime[10] whereas Bantar et al found 48% isolates to be resistant to third generation cephalosporins.[11] 71% isolates of Klebsiella spp. from blood samples have been reported to be resistant to third generation cephalosporins.[9]
In 1976, Sharad Kumar committee had made specific recommendations to form hospital drug policy and infection control committee.[12] For the formulation of such a policy, surveillance of antimicrobial resistance is very essential. Hospital drug policies are of two types: 1) Restrictive policy - this removes selection pressure for the emergence of resistant strains, 2) Rotational policy - periodic changes of antibiotics used in a hospital will avoid the emergence of resistant strains by altering the selection pressure.[13] In 1989 Giamarellou et al conducted a surveillance in Greece on antimicrobial drug resistance and applied a restrictive policy. Drugs used as second line therapy were ordered to pharmacy only after taking approval of hospital infection control committee. This reduced resistance remarkably.[14]
Since drug resistance is so high in hospitals, it is difficult to form empirical therapy. We suggest to use third generation cephalosporins only in dire emergency. In routine, specific therapy should be sought after antimicrobial sensitivity testing. Resistance against second line drugs (third generation cephalosporins, netilmicin, piperacillin, coamoxyclav, amikacin) is very high (more than 30%) and for them a restrictive policy should be followed. Continuous use of WHONET program will go a long way in making effective policies for future. 

 ~ References Top

1.Manual on antimicrobial resistance and susceptibility testing. Division of emerging and other communicable diseases surveillance and control. WHO antimicrobial resistance monitoring programme. WHO, Geneva Sept. 1997.  Back to cited text no. 1    
2.Editorial review. -lactamases and their clinical significance. Hospital Today 2001;6(10).  Back to cited text no. 2    
3.Collee JG, Duguid JP, Fraser AG, Marmion BP, Mackie, MacCartney. Practical Medical Microbiology, 14th Ed., vol. 2, (Churchill and Livingstone, Edinberg). 1996;131-148 and 166-169.  Back to cited text no. 3    
4.Vatopoulos AC, Kalapothaki V, Legakis NJ. The Greek Network for the surveillance of antimicrobial resistance in bacterial nosocomial isolates in Greece; Bulletin WHO. 1999;77(7):595-601.  Back to cited text no. 4    
5.Zhang F, Jin S, Wu Q. Trends and changes in antimicrobial resistance of clinical isolates from 11 hospitals in Beijing area. Chung Hua I Hsueh Tsa chih 1997;77(5):327-231.  Back to cited text no. 5    
6.Manninen R, Eerola E, Huovienen P. Disk diffusion susceptibility tests: need for laboratory specific breakpoints. Scand J Infect Dis 1995;27(1):45-49.  Back to cited text no. 6    
7.Nema S, Premchandani P, Asolkar MV, Chitnis DS. Emerging Bacterial Drug Resistance in Hospital Practice. Indian J Med Sci 1997;51(8):275-280.  Back to cited text no. 7    
8.Rossi A, Galas M, Tokumoto M, Guelfand L, Lopardo H. In vitro activity of trovafloxacin, of other quinolones and of related antimicrobials against clinical isolates. Groupo colaborativo WHONET - Argentina. 1999;59(1):8-16.  Back to cited text no. 8    
9.Valdivieso F, Trucco O, Diaz MC, Ojeda A. Antimicrobial resistance of agents causing urinary tract infections in 11 Chilean hospitals, Pronares Project. ( In process citation ) Rev Med Chil 1999;127(9):1033-1040.  Back to cited text no. 9    
10.Jones RN, Kugler KC, Pfaller MA, Winokur PL. Characteristics of pathogens causing urinary tract infections in hospitals in North America: results from the sentry antimicrobial surveillance programme 1997. Diagn Microbiol Infect Dis 1999;35(1):55-63.  Back to cited text no. 10    
11.Bantar C, Famiglietti A, Goldberg M. Three year surveillance study of nosocomial bacterial resistance in Argentina. Int J Infect Dis 2000;4(2):85-90.  Back to cited text no. 11    
12.Laboratory manual on the investigation of hospital infections with special reference to P.aeruginosa. National Pseudomonas center, AIIMS, 1979.  Back to cited text no. 12    
13.Greenwood D, Richard SCB, John PF. Strategy of antimicrobial chemotherapy. Medical Microbiology; 15th Edition. 1997:627-628.  Back to cited text no. 13    
14.Giamarellou H, Antoniadou A. The effect of monitoring of antibiotic use on decreasing antibiotic resistance in the hospital. Ciba Found Symp 1997;207:76-86.  Back to cited text no. 14  [PUBMED]  
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2004 - Indian Journal of Medical Microbiology
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