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 ~  Abstract
 ~ Introduction
 ~  Materials and Me...
 ~ Results
 ~ Discussion
 ~ Acknowledgments
 ~  References
 ~  Article Tables

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  Table of Contents  
BRIEF COMMUNICATION
Year : 2012  |  Volume : 30  |  Issue : 2  |  Page : 198-202
 

Does antimicrobial use increase the rate of antimicrobial resistance? A one year experience


Department of Infectious Diseases and Clinical Microbiology, Ministry of Health Okmeydani Training and Research Hospital, Istanbul, Turkey

Date of Submission19-Oct-2011
Date of Acceptance16-Jan-2012
Date of Web Publication28-May-2012

Correspondence Address:
H Gedik
Department of Infectious Diseases and Clinical Microbiology, Ministry of Health Okmeydani Training and Research Hospital, Istanbul
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.96692

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 ~ Abstract 

Antimicrobial resistance has been a challenge in all countries. The aim of this study is to ascertain the risk factors that predispose patients to infections with extended spectrum beta lactamase (ESBL)-producing gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA). Patients who were treated in the secondary care hospital due to infections in 2009 and their isolates were evaluated retrospectively. In total, 174 patients and their 189 isolates, which contained 36 ESBL-producing gram-negative bacteria, 112 non-ESBL-producing gram-negative bacteria, and 41 gram-positive bacteria were evaluated retrospectively. Hospitalisation in the previous 3 months, comorbidity, and usage of amoxicillin-clavulanate in the previous 3 months were determined to be the risk factors associated with infections by the ESBL-producing gram-negative bacteria. Hospitalisation was found to be a risk factor for infection with MRSA. Hospitalisation and underlying conditions increase the colonisation with resistant bacteria and resistance rates in the patients, hospitals and communities. An infection control programme should be contemplated not only for hospitals, but also for the greater community.


Keywords: Community-acquired infections, drug resistance, microbial, risk factor


How to cite this article:
Gedik H. Does antimicrobial use increase the rate of antimicrobial resistance? A one year experience. Indian J Med Microbiol 2012;30:198-202

How to cite this URL:
Gedik H. Does antimicrobial use increase the rate of antimicrobial resistance? A one year experience. Indian J Med Microbiol [serial online] 2012 [cited 2019 Jun 17];30:198-202. Available from: http://www.ijmm.org/text.asp?2012/30/2/198/96692



 ~ Introduction Top


Microorganisms have been evolving towards antimicrobial drug resistance, and this evolution has been considered a major challenge to hospitals. However, many articles have revealed that resistant microorganisms have already invaded areas beyond the hospital, such as farms, long-term care facilities and communities in the last decade. [1],[2] Resistant microorganisms related infections have increased with the increasing use of broad-spectrum antibiotics causing a vicious circle between antimicrobial resistance and antimicrobial use. [3] The aim of this study is to ascertain the risk factors that predispose patients to infections with extended spectrum beta lactamase (ESBL)-producing gram-negative bacteria and methicillin-resistant Staphylococcus aureus Scientific Name Search  (MRSA).


 ~ Materials and Methods Top


This case-control study was conducted in a secondary care hospital that has 120 beds without an intensive care unit. Patients who had an infection associated with the following symptoms, fever (>38°C), increased C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) with microbiological culture that yielded bacteria in 2009 were included in this study. Patients were asked about antibiotic usage and other risk factors such as comorbidity and hospitalisation in the previous 3 months, and a consent form was obtained through face-to-face interviews. Patients who could not be interviewed or had incomplete data and/or did not sign the consent form were excluded from this study. Since it could not be precisely determined whether some isolates were acquired from the community or from outpatients in a health care facility, they were evaluated with the outpatients' isolates. Blood samples that were drawn from vein or catheter were inoculated into Bact Alert 3D bottles (bioMιrieux Diagnostics, Marcy l'Etoile, France), and also urine, sputum, wound, conjunctiva, abscess, blood and catheter samples were inoculated onto 5% sheep blood agar (Salubris Inc Pharmaceuticals, İstanbul, Turkey), or chocolate agar (Salubris Inc Pharmaceuticals) and MacConkey agar (Salubris Inc Pharmaceuticals). Identification, susceptibility and presence of ESBL production and methicillin resistance were examined by the Sensititre system (Trek Diagnostic Systems, Cleveland, OH, USA). Patients' demographic features, underlying conditions, antibiotic use including ceftriaxone, cefixim, amoxicillin-clavulanate, quinolones (ciprofloxacin, levofloxacin, moxifloxacin), cefuroxim and amoxycillin in the previous 3 months and hospitalisation in the previous 3 months were evaluated with the isolates.

Statistical analysis was conducted using SPSS, 13.0 (Chicago, IL, USA). Continuous variables were compared by the two-sample t-test and dichotomous variables were compared by Pearson χ2 . Received antimicrobial therapy was grouped into antimicrobials to assure adequate cell counts. Logistic regression analysis was conducted to obtain unadjusted odds ratios and revealed as the odds ratio (OR), 95% confidence interval (CI) and P value.


 ~ Results Top


In total, 174 patients and their 189 isolates, which contained 36 ESBL-producing gram-negative bacteria, 112 non-ESBL-producing gram-negative bacteria and 41 gram-positive bacteria were evaluated retrospectively [Table 1]. The age distribution of the ESBL (+) group was significantly different from the ESBL (−) group (P = 0.0005). ESBL-producing gram-negative bacteria were significantly isolated from patients who were older than 65 years and less than 1 year of age (P = 0.01), from their urine, blood and catheter samples (P = 0.047). Urinary catheter was recorded in 12 patients and 16 patients had undergone surgery in the previous 3 months. Surgical site infection was not reported by physicians according to Center for Disease Control (CDC) criteria. Urinary system malformations and disorders, chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM), chronic renal failure (CRF) and central venous dialysis catheter (CVDC) were the most frequent underlying conditions in the patients. Urinary system malformations and disorders were the most common comorbid factor. There was a significant relationship between recurrent infection with ESBL-producing gram-negative bacteria and underlying conditions (OR = 0.22; 95% CI: 0.66-0.75; P = 0.004). Hospitalisation in the previous 3 months (OR = 4.32; 95% CI: 1.9-9.6; P = 0.0001) and having an underlying condition (OR = 2.3; 95% CI: 1.23-8.1; P = 0.013) were significant risk factors in the ESBL (+) group. Amoxicillin-clavulanate use in the previous 3 months was determined to be a risk factor for infection with ESBL-producing gram-negative bacteria (OR = 3.7; 95% CI: 1.36-10.33; P = 0.005). There was a relationship between hospitalisation in the previous 3 months and usage of those antibiotics which included ceftriaxone, ciprofloxacin, levofloxacin, sulbactam-ampicillin, cefazolin (OR = 2.4; 95% CI: 0.9-6.3; P = 0.04). There was a correlation between ESBL production and resistance to some antibiotics, for example, amoxycillin-clavulanate, ampicillin-sulbactam and others (P = 0.007; Pearson correlation r = 0.71), except for piperacillin-tazobactam (TZP, P > 0.05). Presence of ESBL production correlated with the presence of resistance against at least one of the third-generation antibiotics (P = 0.003; Pearson correlation r = 0.24). ESBL production rates were significantly higher in E. cloacae (P = 0.0001), E. sakazakii (P = 0.003) and A. baumanii (P = 0.003) isolates [Table 1]. Hospitalisation was determined to be a risk factor for infection with MRSA (OR = 1.4; 95% CI: 0.42-1.9; P = 0.02) [Table 2].
Table 1: Characteristics and risk factors associated with antimicrobial resistance of patients who were infected with gram-negative bacteria

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Table 2: Characteristics and risk factors associated with antimicrobial resistance of patients who were infected with gram-positive bacteria

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 ~ Discussion Top


Use of broad-spectrum antibiotics, such as quinolone, penicillin, second- and third-generation cephalosporins, beta-lactam antibiotics combined with beta-lactamase inhibitors, hospitalisation in the previous 3 months with or without antibiotic treatment, being older than 60 years, having DM, being male and being infected by Klebsiella spp. were described as risk factors for community-acquired ESBL-producing gram-negative bacteria infections. [4],[5] Hospitalisation, amoxicillin-clavulanate use and comorbidity were determined to be the risk factors for infection with ESBL-producing gram-negative bacteria in our study. Moreover, underlying conditions predispose patients to recurrent ESBL-producing bacterial infections due to impairment of immunity and frequent antibiotic use. These factors are the selective forces that increase resistance to antibiotics, as was observed in our study. ESBL-producing gram-negative bacteria were significantly isolated from patients who were older than 65 years and less than 1 year. Infections are more frequently seen in these ages because of underlying conditions, immaturity or impairment of immunity. A healthy immune response prevents infection by resistant forms of bacteria. The immune response pressurises the mutant selection window, which contributes to alleviating the negative effects of non-compliance and influences the optimum dosing strategy. [6] If antibiotic drug concentrations in the blood can be sustained at relatively high levels, the synergistic effect between the antibiotics and the immune response will be optimal for reducing the emergence of resistance, especially for immune response situations that are independent from a wide range of bacterial dynamics. [6]

Broad-spectrum antibiotic use selects resistant microorganisms in the patients and hospitals. This selection predisposes patients to infection by resistant microorganism. Patients who have underlying conditions, such as urinary system malformations and disorders, COPD and DM, are prone to infections by resistant bacteria due to immunocom primising conditions, frequent antibiotic use, hospitalisation, colonisation with resistant bacteria, and exposure to nosocomial strains during hospitalisation. Carriage and overgrowth of resistant bacteria in the gut are important steps for the spread of resistant microorganisms into the community. In a study by Filius and colleagues, [7] the rectal colonisation rate decreased during hospitalisation, but after discharge colonisation with Klebsiella spp., Enterobacter spp., Serratia marcescens, and  Pseudomonas aeruginosa Scientific Name Search rains increased. Faecal harbouring of ESBL-producing enterobacteriaceae isolates had reached a considerable point in the healthy population to the extent of 5% in E. coli, 14% in Klebsiella pneumoniae Scientific Name Search  and 20% in  Klebsiella oxytoca Scientific Name Search  study by Gedik and colleagues. [8] History of hospitalisation and medical care were determined to be the risk factors for infection with MRSA in our study. Health care facilities that serve a large population with an insufficient number of healthcare workers are likely to have a higher rate of MRSA infection. [9]

TZP was found to be the only sensitive (beta)-lactam (beta)-lactamase inhibitor antibiotic and its use was not correlated with the development of infections with ESBL-producing gram-negative bacteria in our study. It seems that TZP could be taken into consideration as an option to reduce the rates of infections with ESBL-producing bacteria. However, Burgess and colleagues [10] reported that the clinical cure rate of TZP was only 55% in their study, which involved TZP as the most commonly administered antibiotic for ESBL-producing bacteria-related infections.

Consequently, hospitalisation and underlying conditions increase colonisation by resistant bacteria and increase resistance rates in the patients, hospitals and communities. Infection control programmes should be contemplated not only for hospitals, but also for the greater community.


 ~ Acknowledgments Top


Research was conducted at the Ministry of Health Çan Public Hospital. No person(s) or firm(s) financed this study. The author has no commercial associations that might create a conflict of interest in connection with this article.

 
 ~ References Top

1.Seppala H, Klaukka T, Lehtonen R, Nenonen E, Huovinen P. Outpatient use of erythromycin: link to increased erythromycin resistancein group A streptococci. Clin Infect Dis 1995;21:1378-85.  Back to cited text no. 1
    
2.Andersson DI. Persistence of antibiotic resistant bacteria. Curr Opin Microbiol 2003;6:452-6.   Back to cited text no. 2
    
3.Chiew YF, Yeo SF, Hall LM, Livermore DM. Can susceptibility to an antimicrobial be restored by halting its use? The case of streptomycinversus Enterobacteriaceae. J Antimicrob Chemother 1998;41:247-51.  Back to cited text no. 3
    
4.Colodner R, Rock W, Chazan B, Keller N, Guy N, Sakran W, et al. Risk factors for the development of extended-spectrum beta-lactamase-producing bacteria in nonhospitalized patients. Eur J Clin Microbiol Infect Dis 2004;23:163-7.  Back to cited text no. 4
    
5.Calbo E, Romaný´ V, Xercavins M, Gomez L, Vidal CG, Quintana S, et al . Risk factors for community-onset urinary tract infections due to Escherichia coli harbouring extended-spectrum beta-lactamases. J Antimicrob Chemother 2006;57:780-3.  Back to cited text no. 5
    
6.Handel A, Margolis E, Levin RB. Exploring the role of the immune response in preventing antibiotic resistance. J Theor Biol 2008;256:655-62.  Back to cited text no. 6
    
7.Filius GM, Gyssens I, Kershof I, Roovers PJ, Ott A, Vulto, et al. Colonization and Resistance Dynamics of Gram-Negative Bacteria in Patients during and after Hospitalization. Antimicrob Agents Chemother 2005;49:2879-6.  Back to cited text no. 7
    
8.Gedik H, Yahyaoðlu M, Yörük G, Fincancý M. Extended-Spectrum [beta]-Lactamase Production Rates of Klebsiella spp. and Escherichia coli Strains Isolated From Infections and Fecal Samples of Healthy People. Infect Dis Clin Pract 2010;18:104-6.  Back to cited text no. 8
    
9.Tacconelli E, De Angelis G, Cataldo MA, Pozzi E, Cauda R. Does antibiotic exposure increase the risk of methicillin-resistant Staphylococcus aureus (MRSA) isolation? A systematic review and meta-analysis. J Antimicrob Chemother 2008;61:26-38.  Back to cited text no. 9
    
10.Burgess D S, Hall 2nd RG, Lewis 2 nd JS, Jorgensen JH, Patterson JE. Clinical and Microbiologic Analysis of a Hospital's Extended-Spectrum Beta-Lactamase-Producing Isolates Over a 2-Year Period. Pharmacotherapy 2003;23:10.  Back to cited text no. 10
    



 
 
    Tables

  [Table 1], [Table 2]



 

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