Frequency and factors associated with carriage of multi-drug resistant commensal Escherichia coliamong women attending antenatal clinics in Central India
© Pathak et al.; licensee BioMed Central Ltd. 2013
Received: 2 February 2013
Accepted: 22 April 2013
Published: 2 May 2013
Commensal Escherichia coli are a prominent reservoir of genes coding for antibiotic resistance and also responsible for endogenous infections in pregnant women. We studied the factors in pregnant women associated with carriage of multi-drug resistant (MDR) E. coli and genetic determinants of antibiotic resistance in them.
Women attending to Obstetric and Gynaecology department outpatient clinics for routine antenatal check-up were administered a questionnaire. Peri-anal swabs were collected for culture isolation and identification of E.coil. Antibiotic sensitivity was done using the Kirby-Bauer disc diffusion method as recommended by the CLSI guidelines. MICs for quinolones and third generation cephalosporins were done using the agar dilution method. Genes coding for production of beta lactamses and for the quinolone resistance determinant were screened by polymerase chain reaction. Rep-PCR was done on MDR isolates for detecting possible genetic similarity. Multiple logistic regression models were used to determine the independent factors associated with carriage of MDR isolates.
A total of 710 isolates of E. coli from 710 women (mean age 26 years) were included in the study. Resistance to at least one antibiotic tested was detected in 94% of the E. coli isolates. A total of 109 isolates were ESBL producing and 35 isolates were MDR. In the MDR isolates MIC50 and MIC90 for quinolones and third generation cephalosporins were high for those isolates that carried bla TEM gene (26 isolates) and bla CTX-M gene (24 isolates). Both bla TEM and bla CTX-M genes were detected in 19 isolates. The commonest Plasmid Mediated Quinolone Resistance (PMQR) gene identified was aac(6 ′ )-Ib-cr (n = 23/25). All isolates carrying the PMQR genes were also positive for bla CTX-M and bla TEM gene. Mutations in gyr A and par C genes were present in all 35 MDR isolates. The statistically significant risk factors for carriage of MDR E. coli were graduate or post-graduate education, a self-employed status, a family size of more than 10 members, antibiotic usage in last four weeks, and history of hospitalization in the last four weeks.
The presence of genes coding for extended spectrum of beta lactamases and plasmid mediated quinolone resistance in commensal E. coli is disconcerting. The study provides strong basis good antibiotic stewardship.
The worldwide dissemination of plasmid-borne extended-spectrum beta-lactamases (ESBLs) in Enterobacteriaceae has become a major global public health problem . Inappropriate use of antibiotic is the predominant selection pressure for antibiotic resistance and aids horizontal transfer of bacterial resistance . The spread of multi-resistant strains of bacteria in the community is compounded with a paucity of new classes of antibiotics effective against Gram-negative bacteria like Escherichia coli. E. coli is the most common bacterial cause of urinary tract infections (UTI’s) in women and also a major cause of catheter induced UTI, surgical site infections, intra-abdominal infections and sepsis in all age groups and meningitis in neonates . The recent spread of New Delhi metallo-beta-lactamase-1 (NDM-1) producing bacteria emphasises the fact that resistant bacteria respect no geographical boundaries .
E. coli forms part of the bacteria commensal flora of the human gut. It has been identified as the predominant reservoir of antibiotic resistance genes . Once acquired, these resistance genes are stable and are easily transferable to pathogenic bacteria . The published studies on antibiotic resistance in commensal E. coli in resource-poor settings are limited as resistance monitoring is resource intensive, requires dedicated staff and a well-equipped laboratory [7–9].
During pregnancy many anatomical and physiological changes occur, which also affect the urinary tract. Asymptomatic bacteriuria is reported to occur in 2–10% of pregnancies and E. coli causes 70–80% of them . Most infections are endogenous in origin . Asymptomatic bacteriuria can have serious consequences for the foetus and/or mother . However, knowledge about the risk factors for carriage of resistant E. coli in the women of reproductive age group is lacking in general and especially from India. Screening the commensal E. coli in antenatal women for antibiotic resistance pattern will provide guidelines for empiric therapy especially for sick new-borns. Molecular analysis of these isolates will provide prevalence of antibiotic resistant genes present in E. coli in the community. The aim of the study is to ascertain the factors associated with the carriage of resistant commensal E. coli in pregnant women and further to characterize the genotypic determinants of antibiotic resistance in them.
Study setting, study participants, enrolment and survey procedure
The study was conducted in Obstetrics and Gynaecology outpatient clinics of a teaching and a non-teaching hospital in Ujjain, Madhya Pradesh, India during a 15- month period from November 2007 to February 2009. Both the hospitals cater predominantly to rural populations. Women between 18 to 49 years of age coming for routine antenatal check up were included in the study. Patients requiring emergency admission or with genital infections were not included.
Study participants were interviewed using a questionnaire containing details of patient particulars: age, family size, education, occupation of the main breadwinner, a reported history of antibiotic use in the previous four weeks and reported hospitalization in the previous four weeks. The questionnaire was piloted for one month to ascertain feasibility of data collection and to train the study assistants. Verbal informed consent was obtained from all participants after explaining the purpose of the study. The Ethics Committee of R.D. Gardi Medical College approved the study (approval number 41/ 2007).
Sample collection, isolation and identification of E. coli
Perianal swabbing was done using sterile, moistened cotton swabs. The collected samples were placed in Amies transport media with charcoal (HiMedia, Mumbai, India). Swabs were transported on ice to microbiology diagnostic laboratory within four hours of collection. Swabs were plated on MacConkey agar. All swabs grew E. coli.
E. coli were identified by standard recommonded methods . Five colonies morphologically resembling of E. coli were selected and identified biochemically . A single isolate from the pool of five colonies was selected for further characterization.
Phenotypic determination of antibiotic susceptibility
Antibiotic susceptibility testing was done using the Kirby-Bauer disc diffusion method. Disc strengths were as recommended by Clinical and Laboratory Standards Institute (CLSI) guidelines . The plates were incubated at 35°C for 18 to 24 hours. Diameter and inhibition zones produced by the antibiotic disc were measured to the nearest millimetre. E. coli ATCC 25922 was used as the reference strain. Antibiotics tested were: ampicillin, cefuroxime, ceftriaxone, cefixime, ceftazidime, nalidixic acid, norfloxacin, ciprofloxacin, ofloxacin, gentamicin, amikacin, chloramphenicol, tetracycline, co-trimoxazole, nitrofurantoin, amoxicillin/clavulanate and piperacillin/tazobactum and imipenem. For calculations all isolates showing zone of inhibition indicating intermediate susceptibility were considered resistant. Multi-drug resistance (MDR) isolates were defined as those isolates having co-resistance to at least three different antibiotic classes . Resistance of the MDR isolates was confirmed by Minimum Inhibitory Concentration (MIC) using agar dilution method for quinolones (ciprofloxacin, ofloxacin) and third generation cephalosporins (cefotaxim, ceftazidime) according to CLSI guidelines .
Extended Spectrum Beta-Latamase (ESBL) were detected phenotypically by the combined disc diffusion method with cefotaxime (30µg) and cefotaxime/clavulanic acid (30/10 µg) and ceftazidime (30µg) and ceftazidime/clavulanic acid (30/10 µg) according to CLSI guidelines .
Detection of genotypic determinants for ESBLs and resistance to quinolones
Multiplex Polymerase Chain reactions (PCR) were used to detect genes coding for beta-lactamases. Total bacterial DNA from selected MDR E. coli showing ESBL production phenotypically was extracted by alkaline lysis method . Amplification and identification of ESBL encoding genes (bla CTX-M , bla TEM and bla SHV ) was done using previously described primers .
A separate multiplex PCR was done for detecting plasmid mediated quinolone resistance genes (PMQR; qnrA, qnrB, qnrS, aac(6 ′ )-Ib-cr and qepA) using previously described primers . After PCR amplification, products were visualized under gel documentation system. Chromosomally mediated quinolone resistance was detected using PCR and DNA sequencing of gyr A and par C genes . The purified PCR products were sequenced with ABI 3730XL (Applied Biosystems, USA) sequencer. The nucleic acid sequences were analyzed by Basic Local Alignment Search Tool available at the National Center for Biotechnology database. The nucleic acid sequences were submitted to Genbank (GenBank accession numbers- KC795246 - KC 795255, KC795239 - KC795245, KC788561, KC788562).
Rep-PCR typing of MDR E. coliisolates
The molecular epidemiology of the MDR E. coli was done by Rep-PCR using BOX A1R (5′-CTACGGCAAGGCGACGCTGACG-3′) primers as previously described . PCR analysis was performed on a total of 25 ml reaction mixture using 3 µl of total bacterial DNA, as previously reported. PCR products were then separated by electrophoresis in 1.5% agarose gels with 1XTAE running buffer at 8V/cm for 70 minutes and stained with Ethidium bromide (0.5µg/ml), (Sigma Aldrich), for 30 minutes and visualized using a UV trans-illuminator. DNA molecular weight marker (O’GenerulerTM 100 bp DNA ladder; Fermentas) was used as a molecular size standard. Gel images were normalized, bands were identified and the data were statistically analysed by using Bionumerics software version 3.5 (Applied Maths, Kortrijk, Belgium). Clustering of patterns was performed by Unweighted Pair Group with Arithmetic averages (UPGMA) and dendrogram was created using the Dice Similarity Coefficient .
The data was entered in EpiData Entry (version 3.1) and then transferred to Stata 10.0 (Stata Corp. College Station, Texas, USA) software for statistical analysis. Frequency and percentages are presented for categorical data. Pearson Chi square test with 95% confidence interval (95% CI) was used to calculate odds ratios (OR) for potential risk factors associated with outcome variable carriage of MDR isolates of E. coli. Crude ORs were calculated from two by two tables. Multi-variable logistic regression models were used to calculate adjusted OR in the final model. The dichotomized explanatory variables included were, occupation of the breadwinner (self employed versus salaried), reported antibiotic use in the previous four weeks (yes versus no), reported hospitalization in the previous four weeks (yes versus no). Categorical variables included, age group in years (15 to 19, 20 to 29, 30 to 39 and 40 to 45), family size (less than or equal to 4, 5 to 10 and more than 10 members) and education (illiterate, up-to primary, up-to higher secondary and graduate or post-graduate). A P value less than or equal to 0.05 was considered significant. The goodness of fit for the model was tested by examining the Receiver Operating Characteristics (ROC) curve plot . The area under the ROC curve was 0.944 for the model for MDR E. coli meeting the criteria for excellent model determination .
Study population and enrolment
Multiple logistic regression analysis of factors associated with carriage of multi-drug resistant E. coli among healthy women attending antenatal clinics in two hospitals in Ujjain, India
n = 710
n = 35
OR (95% CI)
Age (in years)b
15 to 19
20 to 29
30 to 39
40 to 45
Up-to higher secondary
Graduate or post graduate
Less than or equal to 4
More than 10
Reported antibiotic usage (last 4 weeks)
Reported Hospitalization (last 4 weeks)
Detection of antibiotic-resistant phenotype and factors associated with carriage of MDR E. coli
Co-resistance pattern of ten antibiotics for 710 E. coli isolates from healthy women attending antenatal clinics in two hospitals, Ujjain, India
Amoxycillin/clav n (%)
MICs of 35 MDR commensal E. coli isolates
MIC 50 (µg/mL)
The statistically significant factors associated with carriage of MDR E. coli are shown in Table 1 and are as follows: “graduate or post-graduate education” Odds Ratio (OR) 3.98 (95% CI 1.05 to 15.10; P = 0.04); “self employed” OR 0.41 (95% CI 0.15 to 1.06; P = 0.05); “family size more than 10 members” OR 4.97 (95% CI 1.51 to 16.33; P = 0.008); reported “antibiotic usage in last four weeks” OR 17.01 (6.35 to 45.51; P < 0.001) and “history of hospitalization in the last four weeks” OR 26.99 (95% CI 10.32 to 70.50; P < 0.001). The statistically significant factors associated with carriage of ESBL producing isolates are: “antibiotic usage in last four weeks” OR 5.21 (3.12 to 11.28; P < 0.001) and “history of hospitalization in the last four weeks” OR 7.82 (95% CI 4.31 to 10.50; P < 0.001).
Detection of antibiotic resistance coding genes
Chromosomally mediated resistance to quinolones was seen in all the 35 isolates based on the presence of gyrA and parC genes. Plasmid mediated resistance to cephalosporins and quinolones was seen in 22/35 (63%). Of these 21 isolates carried the aac(6 ′ )-Ib-cr genes and only one isolate carried the qnrS along with bla CTX-M-15, bla TEM-1 and bla OXA-1 The other qnrA and qnrS genes carrying plasmid were seen along with the plasmid coding for cephalosporin resistance. Details of MDR isolates along with MIC values are included in the supplementary data (Additional file 1: Table S1). The dendrogram (Figure 1) depicts the genetic similarity of MDR E .coli. The genes coding for plasmid mediated and chromosomally mediated resistance to cephalosporins and quinolones are also depicted at Figure 1.
In the present study it was found that out of the 710 E. coli isolated from women attending antenatal clinics in Ujjain, India 94% were resistant to at least one of the antibiotic groups tested. The statistically significant factors associated with carriage of MDR E. coli were better education, overcrowding (family size more than 10 members) history of antibiotic use and/or hospitalization in the last four weeks.
Quinolone resistance is usually chromosomally mediated . All 35 multi-resistant isolates showed presence of gyrA and parC genes, which are chromosomally mediated. The aac(6 ′ )-Ib-cr gene accounted for 95% of the PMQR genes. Similar findings in pathogenic E. coli have been reported elsewhere in India  and in E. coli isolated from hospital wastewater in our setting . Plasmid mediated resistance to cephalosporins was largely due to bla CTX-M -15 which is in keeping with other studies done in India [21, 23]. The bla TEM-1 is not been subtyped therefore no comment can be made for its co-relation with ESBL production. It is interesting to note that bla SHV was not detected. The presence of genes coding for extended spectrum of beta lactamases and plasmid mediated quinolone resistance in commensal E. coli is disconcerting.
Studies from India [7, 24] and other low-middle income countries  have reported lower rates of resistance (range of 32 to 63%) to a single antibiotic compared to the present study (94%). The difference in the resistance rates could be due to variation in the geographical area of the study [7, 8, 26] and also is dependent on the pattern of antibiotic prescribing in the local community [27, 28]. The ESBL rate (15%) in the present study is lower than that reported among pathogenic E. coli (69%) isolated from patients with clinical infections in the same geographical area .
The majorities of women enrolled in the study were either illiterate or had only a primary education (Table 1). Women with higher education had a higher likelihood of carriage of MDR E. coli. This could be a chance association and needs further validation. But, women with higher education may also be socio-economically better off and thus more likely to seek health-care and consequently have a greater exposure to antibiotics . Most self-employed women enrolled in the study were daily wage workers, and consequently, probably, had limited opportunity to seek medical care, limiting their antibiotic exposure.
Exposure to hospital environment especially hospitalization in intensive care units is a major risk factor for carriage of multi-drug resistant bacteria especially in resource poor settings where hospitals can have high infection rates and spread of multi-drug resistant pathogens [25, 31]. A multitude of factors including poor infrastructure of hospitals, low compliance with hand-hygiene, heavy workload with understaffing, overcrowding, lack of or poorly functioning infection control programme contribute to the problem .
In the present study a significantly higher MDR carriage among women living in larger families (more than 10 members), OR 4.97 (95% CI 1.51 to 16.33; P = 0.008) was found. Similar results have been reported in postmenopausal women in our setting . Over-crowding combined with inadequate hygiene and sanitary facilities and sewage disposal, would lead to greater sharing of commensal flora in families and communities [8, 32]. In a study among primary school children in rural Tamil Nadu over crowding in classrooms was associated with increased carriage of antibiotic resistant commensal E. coli. Thus, the dynamics of bacterial transmission due to over crowding is worthy of further investigation.
The rate and amount of antibiotic use in community an important determinant of increasing antibiotic resistance in bacteria [27, 28]. A meta analysis and review on the effect of antibiotic prescribing in a primary-care setting on antimicrobial resistance in individual patients included five studies of urinary tract infections (14348 participants), the pooled odds ratio (OR) for resistance was 2.5 (95% CI 2.1 to 2.9) within two months of antibiotic treatment . The OR at one month (only one study) was 6.1 (95% CI 2.8 to 13.4) . Recent antibiotic use was associated with increased risk of carriage of resistant E. coli, OR 1.8 (95% CI 1.5 to 2.3) in a study from Indonesia .
The ESBL production is the commonest mechanism of resistance to cephalosporins in Enterobacteriaceae. Phenotypic detection of ESBL production was in 15% isolates in the present study, which is much lower than the 51% reported in a study from China .
The bla CTX-M-15 and bla TEM −1 coded genes are widespread in E. coli. The detection of bla CTX-M-15 and bla TEM-1 genes as shown in Figure 1 is similar to that in Latin America . In the present study it has been noted that a majority of MDR E coli isolates (48%) were carrying aac(6 ′ )-Ib-cr gene. These isolates also showed high MIC to ciprofloxacin and ofloxacin probably due to chromosomally mediated resistance (par A and par C) (Table 3). Co-residence of bla CTX-M-15, qnr and aac(6 ′ )-Ib-cr genes on the same plasmid has been reported elsewhere .
PMQR genes code for low levels of quinolone resistance . The presence of PMQR gene in MDR isolates was 4%, which is similar to that in a study from Republic of Korea . It is interesting to notice that chromosomal mediated quinolone resistance coded by mutation in QRDR regions of gyr A and par C genes was present in all MDR E coli isolates in the present study. A study in Ghana on quinolone-resistant E. coli in the faecal flora also reported the presence of qnr genes and amnio acid substitutions at gyrA and par C genes .
An analysis of resistance pattern of commensal E. coli can be helpful in deciding empiric treatment of choice for suspected neonatal infections. Neonatal sepsis with multi-drug resistant gram negative organisms resistant to ampicillin, third generation cephalosporins and gentamicin caused high mortality (26%) in neonates in a neonatal intensive care unit (NICU) in India . The current choices of therapy in our NICU are in line with the most sensitive patterns described ie third generation cephalosporins along with an aminoglycoside (Table 2). However, the last resort antibiotics (eg. vancomycin and imipenem) are now increasingly being used in view of increasing resistance  in our NICU to salvage septic neonates.
The most important strength of this study is the combination of epidemiological and molecular methods for the identification of factors associated with carriage of resistant bacteria. Antenatal women are a population, which is at a low risk for receiving antibiotics. Despite this a history of antibiotic therapy was identified as an important risk factor associated with carriage of resistant bacteria. The fact underscores the importance of prudent antibiotic use. A structured questionnaire was used which could have resulted in us missing other factors related to carriage of resistant E. coli like environmental factors and food chain related factors.
The presence of antibiotic resistance mediating genes in commensal bacteria provides information on the occurrence of multi-drug resistance bacteria in a given geographical area. The presence of genes coding for extended spectrum of beta lactamases and plasmid mediated quinolone resistance in commensal E. coli is disconcerting.
This is compounded in resource poor settings with overcrowding and poor sanitation, which seem to aid the spread of multi-drug resistant bacteria within a community. This provides strong basis of good antibiotic stewardship.
We thank all the participating physicians and patients for their co-operation during data collection and Dr VK Mahadik, Medical Director, RD Gardi Medical College, for administrative support during the project. This project is funded by the VR (the Swedish Research Council) and the Asia link. We thank the Erasmus Mundus External Cooperation Window lot 15 and The Swedish Research School for Global Health for scholarships to AP for his doctoral studies at Division of Global Health (IHCAR), Karoliska Institutet, Sweden. We also thank Sathish Mundayoor and Biljo V. Joseph at RGCB, Thiruvananthapuram, Kerala for providing support for BioNumerics software analysis.
- Schultsz C, Geerlings S: Plasmid-mediated resistance in enterobacteriaceae: changing landscape and implications for therapy. Drugs. 2012, 72 (1): 1-16. 10.2165/11597960-000000000-00000.View ArticlePubMedGoogle Scholar
- Bailey JK, Pinyon JL, Anantham S, Hall RM: Commensal Escherichia coli of healthy humans: a reservoir for antibiotic-resistance determinants. J Med Microbiol. 2011, 59 (Pt 11): 1331-1339.Google Scholar
- Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, Scheld M, Spellberg B, Bartlett J: Bad bugs, no drugs: no ESKAPE! an update from the infectious diseases society of america. Clin Infect Dis. 2009, 48 (1): 1-12. 10.1086/595011.View ArticlePubMedGoogle Scholar
- Ron EZ: Distribution and evolution of virulence factors in septicemic Escherichia coli. Int J Med Microbiol. 2010, 300 (6): 367-370. 10.1016/j.ijmm.2010.04.009.View ArticlePubMedGoogle Scholar
- Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, Chaudhary U, Doumith M, Giske CG, Irfan S: Emergence of a new antibiotic resistance mechanism in india, pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis. 2010, 10 (9): 597-602. 10.1016/S1473-3099(10)70143-2.View ArticlePubMedPubMed CentralGoogle Scholar
- Ewers C, Bethe A, Semmler T, Guenther S, Wieler LH: Extended-spectrum beta-lactamase-producing and AmpC-producing Escherichia coli from livestock and companion animals, and their putative impact on public health: a global perspective. Clin Microbiol Infect. 2012, 18 (7): 646-655. 10.1111/j.1469-0691.2012.03850.x.View ArticlePubMedGoogle Scholar
- Mathai E, Chandy S, Thomas K, Antoniswamy B, Joseph I, Mathai M, Sorensen TL, Holloway K: Antimicrobial resistance surveillance among commensal Escherichia coli in rural and urban areas in southern india. Trop Med Int Health. 2008, 13 (1): 41-45. 10.1111/j.1365-3156.2007.01969.x.View ArticlePubMedGoogle Scholar
- Nys S, Okeke IN, Kariuki S, Dinant GJ, Driessen C, Stobberingh EE: Antibiotic resistance of faecal Escherichia coli from healthy volunteers from eight developing countries. J Antimicrob Chemother. 2004, 54 (5): 952-955. 10.1093/jac/dkh448.View ArticlePubMedGoogle Scholar
- Pallecchi L, Bartoloni A, Fiorelli C, Mantella A, Di Maggio T, Gamboa H, Gotuzzo E, Kronvall G, Paradisi F, Rossolini GM: Rapid dissemination and diversity of CTX-M extended-spectrum beta-lactamase genes in commensal Escherichia coli isolates from healthy children from low-resource settings in latin america. Antimicrob Agents Chemother. 2007, 51 (8): 2720-2725. 10.1128/AAC.00026-07.View ArticlePubMedPubMed CentralGoogle Scholar
- Schnarr J, Smaill F: Asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy. Eur J Clin Invest. 2008, 38 (Suppl 2): 50-57.View ArticlePubMedGoogle Scholar
- Murray PRBE, Pfaller MA, Tenover FC, Yolken RH: Manual of clinical microbiology. 1999, Washington DC: ASM press, 7Google Scholar
- Clinical and Laboratory Standards Institute: M100-S20-U. Performance standards for antimicrobial susceptibility testing: 20th informational supplement. 2010, Wayne, PA: CLSIGoogle Scholar
- Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B: 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 (3): 268-281. 10.1111/j.1469-0691.2011.03570.x.View ArticlePubMedGoogle Scholar
- Sambrook JFE, Maniatis T: Molecular cloning: a laboratory manual. 1989, NY, USA: Cold Spring Harbor Laboratory PressGoogle Scholar
- Dallenne C, Da Costa A, Decre D, Favier C, Arlet G: Development of a set of multiplex PCR assays for the detection of genes encoding important beta-lactamases in enterobacteriaceae. J Antimicrob Chemother. 2010, 65 (3): 490-495. 10.1093/jac/dkp498.View ArticlePubMedGoogle Scholar
- Kim HB, Park CH, Kim CJ, Kim EC, Jacoby GA, Hooper DC: Prevalence of plasmid-mediated quinolone resistance determinants over a 9-year period. Antimicrob Agents Chemother. 2009, 53 (2): 639-645. 10.1128/AAC.01051-08.View ArticlePubMedGoogle Scholar
- Everett MJ, Jin YF, Ricci V, Piddock LJ: Contributions of individual mechanisms to fluoroquinolone resistance in 36 Escherichia coli strains isolated from humans and animals. Antimicrob Agents Chemother. 1996, 40 (10): 2380-2386.PubMedPubMed CentralGoogle Scholar
- Goldberg TL, Gillespie TR, Singer RS: Optimization of analytical parameters for inferring relationships among Escherichia coli isolates from repetitive-element PCR by maximizing correspondence with multilocus sequence typing data. Appl Environ Microbiol. 2006, 72 (9): 6049-6052. 10.1128/AEM.00355-06.View ArticlePubMedPubMed CentralGoogle Scholar
- Lemeshow S, Hosmer DW: A review of goodness of fit statistics for use in the development of logistic regression models. Am J Epidemiol. 1982, 115 (1): 92-106.PubMedGoogle Scholar
- Li XZ: Quinolone resistance in bacteria: emphasis on plasmid-mediated mechanisms. Int J Antimicrob Agents. 2005, 25 (6): 453-463. 10.1016/j.ijantimicag.2005.04.002.View ArticlePubMedGoogle Scholar
- Shahid M, Singh A, Sobia F, Rashid M, Malik A, Shukla I, Khan HM: bla(CTX-M), bla(TEM), and bla(SHV) in enterobacteriaceae from north-indian tertiary hospital: high occurrence of combination genes. Asian Pac J Trop Med. 2011, 4 (2): 101-105. 10.1016/S1995-7645(11)60046-1.View ArticlePubMedGoogle Scholar
- Diwan V, Chandran SP, Tamhankar AJ, Stalsby Lundborg C, Macaden R: Identification of extended-spectrum beta-lactamase and quinolone resistance genes in Escherichia coli isolated from hospital wastewater from central india. J Antimicrob Chemother. 2012, 67 (4): 857-859. 10.1093/jac/dkr564.View ArticlePubMedGoogle Scholar
- Pazhani GP, Chakraborty S, Fujihara K, Yamasaki S, Ghosh A, Nair GB, Ramamurthy T: QRDR mutations, efflux system & antimicrobial resistance genes in enterotoxigenic Escherichia coli isolated from an outbreak of diarrhoea in ahmedabad, india. Indian J Med Res. 2011, 134: 214-223.PubMedPubMed CentralGoogle Scholar
- Seidman JC, Anitha KP, Kanungo R, Bourgeois AL, Coles CL: Risk factors for antibiotic-resistant E. Coli in children in a rural area. Epidemiol Infect. 2009, 137 (6): 879-888. 10.1017/S0950268808001519.View ArticlePubMedGoogle Scholar
- Duerink DO, Lestari ES, Hadi U, Nagelkerke NJ, Severin JA, Verbrugh HA, Keuter M, Gyssens IC, van den Broek PJ: Determinants of carriage of resistant Escherichia coli in the indonesian population inside and outside hospitals. J Antimicrob Chemother. 2007, 60 (2): 377-384. 10.1093/jac/dkm197.View ArticlePubMedGoogle Scholar
- Sahoo KC, Tamhankar AJ, Sahoo S, Sahu PS, Klintz SR, Lundborg CS: Geographical variation in antibiotic-resistant Escherichia coli isolates from stool, cow-dung and drinking water. Int J Environ Res Public Health. 2012, 9 (3): 746-759.View ArticlePubMedPubMed CentralGoogle Scholar
- Pathak A, Mahadik K, Dhaneria SP, Sharma A, Eriksson B, Lundborg CS: Surveillance of antibiotic consumption using the “focus of infection” approach in 2 hospitals in ujjain india. PLoS One. 2012, 7 (6): e38641-10.1371/journal.pone.0038641.View ArticlePubMedPubMed CentralGoogle Scholar
- Goossens H, Ferech M, Vander Stichele R, Elseviers M: Outpatient antibiotic use in europe and association with resistance: a cross-national database study. Lancet. 2005, 365 (9459): 579-587.View ArticlePubMedGoogle Scholar
- Pathak A, Marothi Y, Kekre V, Mahadik K, Macaden R, Lundborg CS: High prevalence of extended-spectrum beta-lactamase-producing pathogens: results of a surveillance study in two hospitals in ujjain, india. Infect Drug Resist. 2012, 5: 65-73.View ArticlePubMedPubMed CentralGoogle Scholar
- Mishra SK, Mukhopadhyay S: Socioeconomic correlates of reproductive morbidity among adolescent girls in sikkim india. Asia Pac J Public Health. 2012, 24 (1): 136-150. 10.1177/1010539510375842.View ArticlePubMedGoogle Scholar
- Alp E, Leblebicioglu H, Doganay M, Voss A: Infection control practice in countries with limited resources. Ann Clin Microbiol Antimicrob. 2011, 10: 36-10.1186/1476-0711-10-36.View ArticlePubMedPubMed CentralGoogle Scholar
- Pathak A, Mahadik K, Sharma R, Marothi Y, Sharma M, Macaden R, Lundborg CS: Factors associated with carriage of multi-resistant commensal Escherichia coli among postmenopausal women in Ujjain, India. Scand J Infect Dis. 2012, 44 (12): 973-977. 10.3109/00365548.2012.697635.View ArticlePubMedGoogle Scholar
- Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD: Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ. 2010, 340: c2096-10.1136/bmj.c2096.View ArticlePubMedGoogle Scholar
- Li B, Sun JY, Liu QZ, Han LZ, Huang XH, Ni YX: High prevalence of CTX-M beta-lactamases in faecal Escherichia coli strains from healthy humans in fuzhou china. Scand J Infect Dis. 2011, 43 (3): 170-174. 10.3109/00365548.2010.538856.View ArticlePubMedGoogle Scholar
- Jiang Y, Zhou Z, Qian Y, Wei Z, Yu Y, Hu S, Li L: Plasmid-mediated quinolone resistance determinants qnr and aac(6′)-Ib-cr in extended-spectrum beta-lactamase-producing Escherichia coli and klebsiella pneumoniae in china. J Antimicrob Chemother. 2008, 61 (5): 1003-1006. 10.1093/jac/dkn063.View ArticlePubMedGoogle Scholar
- El Salabi A, Walsh TR, Chouchani C: Extended spectrum beta-lactamases, carbapenemases and mobile genetic elements responsible for antibiotics resistance in gram-negative bacteria. Crit Rev Microbiol. 2013, 39 (2): 113-122. 10.3109/1040841X.2012.691870.View ArticlePubMedGoogle Scholar
- Namboodiri SS, Opintan JA, Lijek RS, Newman MJ, Okeke IN: Quinolone resistance in Escherichia coli from accra ghana. BMC Microbiol. 2011, 11: 44-10.1186/1471-2180-11-44.View ArticlePubMedPubMed CentralGoogle Scholar
- Viswanathan R, Singh AK, Basu S, Chatterjee S, Sardar S, Isaacs D: Multi-drug resistant gram negative bacilli causing early neonatal sepsis in india. Arch Dis Child Fetal Neonatal Ed. 2012, 97 (3): F182-187. 10.1136/archdischild-2011-300097.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/199/prepub