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Background: Enteric fever remains a major cause of morbidity and mortality in Nepal. The emergence of multi-drug resistant Salmonella is a challenge to the clinician to care for patients with enteric fever. This study assessed the antibiotic susceptibility of Salmonella Typhi isolated from enteric fever and the presence of gyrA? ?gene mutation at ser83 of S. Typhi., Methods: Blood samples (n = 834) from suspected enteric fever patients were collected and cultured to identify Salmonella Typhi. Antimicrobial sensitivity test was performed by the modified Kirby Bauer disc diffusion method. The minimum ?inhibitory concentration (MIC) tests for ofloxacin and ciprofloxacin were examined by the agar dilution method. The gyrA gene was amplified by PCR and restriction enzyme digestion was performed to evaluate the ser83 mutation., Results: Among 824 blood samples analyzed, 5.1% (42/824) were culture positive for S. Typhi. First-line antibiotics chloramphenicol and co-trimoxazole showed higher in-vitro efficacy compared to amoxicillin. Macrolides (azithromycin) and third-generation cephalosporins (ceftriaxone, cefixime, and cefotaxime) were highly effective against S. Typhi. Nalidixic acid resistance (NAR) was observed in 95.2% (40/42) isolates, among them, all (40/40) isolates harbored mutant gyrA gene at ser83. However, none of the nalidixic acid-sensitive Salmonella? isolates was positive for gyrA? mutation at ser83., Conclusions: This study showed decreased susceptibility to fluoroquinolones and the presence of gyrA? mutation at ser83 position in majority of S. Typhi isolates which highlights the importance of alternate drugs as empirical therapy for the treatment of enteric fever patients. So, the clinician should focus on prescribing conventional first-line antibiotics for the treatment of typhoid patients after higher cohort and extended follow-up studies.

Introduction: With increasing fluoroquinolone resistance, extended spectrum cephalosporins are recommended for the treatment of invasive Salmonella infections. However, Extended spectrum beta-lactamases (ESBL) producing Salmonella Paratyphi A causing enteric fever is on the rise and constitutes a major therapeutic challenge. Hence, we aimed to assess the incidence of ESBL production, fluoroquinolone resistance in S. Paratyphi A and to compare the fluoroquinolone resistance detection methods., Methodology: Seventeen blood-culture isolates of S. Paratyphi A were tested for susceptibility to ampicillin, chloramphenicol, co-trimoxazole, streptomycin and tetracycline (ACCuST), fluoroquinolones, azithromycin and ceftriaxone by disk diffusion method. We compared and correlated between disk diffusion of ciprofloxacin and pefloxacin with ciprofloxacin MIC. Combined disk test was employed to determine ESBL production., Results: In this study, 13(76.5%) isolates were nalidixic acid resistant (NAR), 16 (94.1%) were pefloxacin resistant, while 7 (41.2%), 9 (52.9%) exhibited resistance and intermediate susceptibility to ciprofloxacin respectively. The MIC50, MIC90 of ciprofloxacin was 1 µg/mL, 2 µg/mL respectively. Among the NAR, 76.92% were DSC (MIC 0.5-1 µg/mL) and 23.08% had an MIC of 2-4 µg/mL. Of note, 4 isolates with DSC were NAS. Of the 17 S. Paratyphi A isolates, 14 (82.4%) were ESBL producers and 11 (64.7%) isolates were ceftriaxone susceptible., Conclusions: Multidrug resistant (AmpRChlRSxtR) S. Paratyphi A with combined resistance to fluoroquinolones and ESBL production is a cause of concern. We found S. Paratyphi A isolates with a relatively unusual phenotype: nalidixic acid susceptible but exhibited DSC; pefloxacin susceptible but ciprofloxacin resistant. Of note one multidrug resistant (AmpRChlRSxtR) isolate, an ESBL producer exhibited resistance to azithromycin, cephalosporins and fluoroquinolones but was susceptible to carbapenems and streptomycin., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 Rajan Prabhurajan, R Mary Esther Selvam, Kesavaram Padmavathy.)

The rapid rise of antibiotic resistance, combined with the increasing cost and difficulties to develop new antibiotics, calls for treatment strategies that enable more sustainable antibiotic use. The development of such strategies, however, is impeded by the lack of suitable experimental approaches that allow testing their effects under realistic epidemiological conditions. Here, we present an approach to compare the effect of alternative multidrug treatment strategies in vitro using a robotic liquid-handling platform. We use this framework to study resistance evolution and spread implementing epidemiological population dynamics for treatment, transmission, and patient admission and discharge, as may be observed in hospitals. We perform massively parallel experimental evolution over up to 40 d and complement this with a computational model to infer the underlying population-dynamical parameters. We find that in our study, combination therapy outperforms monotherapies, as well as cycling and mixing, in minimizing resistance evolution and maximizing uninfecteds, as long as there is no influx of double resistance into the focal treated community., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Objectives: Since the early 2000s, Escherichia coli resistance to third-generation cephalosporins (3GCs) has been increasing in all European countries, mainly due to the spread of extended spectrum β-lactamases (ESBLs). Here we present a retrospective study that combines resistance of E. coli to 3GCs and quinolones with data on antibiotic use in the community in a region of Northeastern France., Methods: Since 2012, an observational surveillance of antimicrobial resistance and antibiotic use in the community was conducted: data on antimicrobial resistance in E. coli isolates were collected from 11 private laboratories, and consumption data were collected from the three main healthcare insurances., Results: A significant decrease in the prevalence of resistance to 3GCs (from 5.6% to 4.2%; P < 0.001), nalidixic acid (from 16.7% to 14.8%; P = 0.004) and ciprofloxacin (from 10.9% to 8.1%; P < 0.001) was reported between 2015 and 2017. Although total antibiotic consumption did not vary significantly between 2012 and 2017, a decrease in the consumption of 3GCs (-32.%; P < 0.001) and quinolones (-25.5%; P < 0.001) was observed., Conclusion: Here we report a decrease in the prevalence of E. coli isolates resistant to 3GCs and quinolones in outpatients in the context of significant decreasing consumption of these two antibiotic classes., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Atopic dermatitis (AD) is an inflammatory skin disease with an associated barrier dysfunction and Staphylococcus aureus infection. The mainstay steroid and calcineurin inhibitor therapy shows some adverse effects. 2,4-Dimethoxy-6-methylbenzene-1,3-diol (DMD) is a benzenoid isolated from Antrodia camphorata., Objective: We investigated the inhibitory effect of DMD on methicillin-resistant S. aureus (MRSA), the chemokine production in stimulated keratinocytes, and the AD-like lesion found in ovalbumin (OVA)-sensitized mice., Methods: The antimicrobial effect and cutaneous barrier function were evaluated using an in vitro culture model and an in vivo mouse model of AD-like skin., Results: DMD exhibited a comparative minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against MRSA with nalidixic acid, a conventional antibiotic. The MIC and MBC for DMD was 78.1 and 156.3 μg/ml, respectively. DMD also showed the ability to eliminate the clinical bacteria isolates with resistance to methicillin and vancomycin. The DNA polymerase and gyrase inhibition evoked by DMD for bacterial lethality was proposed. In the activated keratinocytes, DMD stopped the upregulation of chemokines (CCL5 and CCL17) and increased the expression of differentiation proteins (filaggrin, involucrin, and integrin β-1). Topical application of DMD facilely penetrated into the skin, with AD-like skin displaying 2.5-fold greater permeation than healthy skin. The in vivo assessment using the mouse model with OVA sensitization and MRSA inoculation revealed a reduction of transepidermal water loss (TEWL) and bacterial burden by DMD by about 2- and 100-fold, respectively. Differentiation proteins were also restored after topical DMD delivery., Conclusion: Our data demonstrated an advanced concept of AD treatment by combined barrier repair and bacterial eradication with a sole agent for ameliorating the overall complications., (Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

The epidemiology of typhoid fever in South Asia has changed. Multi-drug resistant (MDR) Salmonella typhi ( S. typhi) is now frequently resistant to nalidixic acid and thus labelled NARST. Treatment failure with the use of fluoroquinolones has been widely noted, forcing clinicians to adopt alternative treatment strategies. In this observational study, we looked at various treatment regimens and correlated clinical and microbiological outcomes. In 146 hospitalised adults, the median minimum inhibitory concentration (MIC) for ciprofloxacin was 0.38 µg/mL with a median fever clearance time (FCT) of eight days (range = 2-35 days). Of the regimens used, gatifloxacin and azithromycin had a shorter FCT of six days compared to ceftriaxone (ten days; P < 0.001). Though mortality and relapse in our cohort was low, NARST seemed to correlate with mortality ( P = 0.006). Gatifloxacin or azithromycin clearly emerge as the drugs of choice for treatment of typhoid in South India.

The emergence of extended-spectrum beta-lactamases (ESBL) producing strains become a great concern, because few antimicrobial agents remain active against them. Due to the lack of data on the genotyping characteristics and antibiotics resistance of clinical isolates of Klebsiella pneumoniae in the north of Iran, this study aimed to determine the occurrence of ESBL-producing isolates and their molecular characteristics in order to analyses their epidemiological relationships. This cross-sectional study performed on 60 K. pneumoniae isolates which were recovered from different clinical specimens within May and November 2016. Isolates were identified by standard microbiologic tests and confirmed by API 20E strip. Antimicrobial susceptibility testing was carried out by disk diffusion method. The genetic relatedness among the isolates was assessed by RAPD-PCR. Totally, the lowest level of susceptibility was toward amoxicillin/clavulanat, and nalidixic acid. On the other hand, the highest level of susceptibility was toward imipenem (86.7%). The rate of ESBL-producing isolates was 45% (27/60). There was a significant association between production of ESBLs and higher antibiotic resistance in tested isolates. The RAPD-PCR dendrogram revealed 5 major clusters with a similarity of 80% which indicates the high relatedness of the studied isolates. Twenty-one isolates out of the 27 ESBL-producing isolates were clustered in cluster A. In summary, results showed the high prevalence of multiple-drug resistant and ESBL-producing K. pneumoniae isolates in our ICUs. Also, results revealed a significant similarity between ESBL-producing isolates that necessitate restricted infection control policies and rational prescription and use of antibiotics.

We previously found that the hospital use of tetracyclines is associated with quinolone resistance in hospital isolates of Enterobacteriaceae. Tetracyclines are heavily used in the community. Our aim was to assess whether their use in the community favors quinolone resistance in community isolates of Escherichia coli. Monthly data of community antibiotics use and E. coli quinolone resistance in a 1.3 million inhabitant French area were obtained from 2009 to 2014, and were analyzed with autoregressive integrated moving average (ARIMA) models. Quinolone use decreased from 10.1% of the total antibiotic use in 2009 to 9.3% in 2014 (trend, - 0.016; p-value < 0.0001), while tetracycline use increased from 16.5% in 2009 to 17.1% in 2014 (trend, 0.016; p < 0.0001). The mean (95% confidence interval) monthly proportions of isolates that were non-susceptible to nalidixic acid and ciprofloxacin were 14.8% (14.2%-15.5%) and 9.5% (8.8%-10.1%), respectively, with no significant temporal trend. After adjusting on quinolone use, tetracycline use in the preceding month was significantly associated with nalidixic acid non-susceptibility (estimate [SD], 0.01 [0.007]; p-value, 0.04), but not with ciprofloxacin non-susceptibility (estimate [SD], 0.01 [0.009]; p-value, 0.23). Tetracycline use in the community may promote quinolone non-susceptibility in E. coli. Decreasing both tetracycline and quinolone use may be necessary to fight against the worldwide growth of quinolone resistance.

Therapeutic options with quinolones are severely compromised in infections caused by members of Enterobacteriaceae family. Mutations in chromosomal region are one of the major reasons for bacterial resistance towards this group of antibiotic. The aim of the study is to detect the mutations in gyr A and par C responsible for quinolone resistance among clinical isolates of Escherichia coli. A total of 96 quinolone-resistant clinical isolates of E. coli were collected from a tertiary care hospital of North-east India during March 2015 to August 2015. All the quinolone-resistant E. coli strains were investigated for mutations in the topoisomerases genes gyrA and parC by amplifying and sequencing the quinolone resistance determining regions. Among the 96 E. coli isolates, 83.3% were resistant to nalidixic acid and 80.2%, 66.6%, 23.9% and 50% to ciprofloxacin, norfloxacin, levofloxacin and ofloxacin, respectively. Several alterations were detected in gyrA and parC genes. Three new patterns of amino acid substitution are reported in E. coli isolates. The findings of this study warrant a review in quinolone-based therapy in this region of the world to stop or slow down the irrational use this drug., Competing Interests: There are no conflicts of interest

Little is known about the epidemiology of typhoid and paratyphoid fever in Nepal. We aimed to elucidate the molecular and clinical epidemiology of Salmonella Paratyphi A in Nepal. Isolates were collected from 23 cases of bacteremia due to S. Paratyphi A between December 2014 and October 2015. Thirteen patients (57%) were male, and the median age was 21 years. None of the patients had an underlying chronic disease. All S. Paratyphi A isolates were sensitive to ampicillin, trimethoprim/sulfamethoxazole, ceftriaxone, and chloramphenicol. All isolates were resistant to nalidixic acid and were categorized as intermediately susceptible to levofloxacin. Phylogenetic analysis revealed close relatedness among the isolates, including several clonal groups, suggesting local spread. Patients with bacteremia due to S. Paratyphi A in Kathmandu, Nepal, were relatively young and nondebilitated. Improving control of S . Paratyphi infections should focus on effective infection control measures and selection of empirical therapy based on current resistance patterns.

Background & Objectives: Aeromonas species have been reported to cause various illnesses in humans such as wound infections, septicaemia, peritonitis and pneumonia. Their role in causation of cholera-like illness is also being increasingly recognized. This retrospective study was done to know the presence of Aeromonas as a cause of acute diarrhoea in a tertiary care hospital and to find the common species of Aeromonas causing diarrhoea and their antibiotic susceptibility patterns., Methods: Fifty isolates of Aeromonas were obtained over a period of 15 yr from 2000 to 2014 from patients of suspected acute gastroenteritis resembling cholera. Biotyping was done for 35 of these isolates available in culture collection, based on a panel of 13 biochemical reactions. Antibiogram was put up for all of these isolates by disk diffusion methods and interpreted according to the Clinical and Laboratory Standards Institute guidelines., Results: Of the 50 patients of Aeromonas-related acute gastroenteritis, 13 (26%) had typical features of cholera with rice water stools and severe dehydration. Eight patients (16%) had dysentery-like picture. One patient died of severe dehydration and septicaemia. The most common species were found to be Aeromonas caviae (34%) followed by Aeromonas veronii biovar veronii (29%), Aeromonas veronii biovar sobria (26%) and Aeromonas hydrophila (9%). All tested isolates were uniformly susceptible to cefepime, amikacin, azithromycin and meropenem; 14 per cent were susceptible to amoxicillin, 32 per cent to nalidixic acid, 60 per cent to co-trimoxazole, 54 per cent to ciprofloxacin, 60 per cent to ofloxacin, 74 per cent to chloramphenicol, 76 per cent to ceftriaxone, 74 per cent to cefotaxime, 88 per cent to gentamicin and 86 per cent to furoxone., Interpretation & Conclusions: Aeromonas is an important, often neglected pathogen capable of causing a variety of gastrointestinal tract symptoms such as acute diarrhoea and dysentery and may even mimic cholera. It is, therefore, pertinent to recognize this pathogen as an important agent in the causation of severe diarrhoea.

This first nationwide study was conducted to analyze the prevalence of plasmid-mediated quinolone resistance (PMQR) genes in phenotypically unselected (consecutive) clinical enterobacteria. We studied 1,058 isolates that had been consecutively collected in 66 hospitals of the WHONET-Argentina Resistance Surveillance Network. Overall, 26% of isolates were nonsusceptible to at least one of the three quinolones tested (nalidixic acid, ciprofloxacin, and levofloxacin). The overall prevalence of PMQR genes was 8.1% (4.6% for aac(6')-Ib-cr; 3.9% for qnr genes; and 0.4% for oqxA and oqxB, which were not previously reported in enterobacteria other than Klebsiella spp. from Argentina). The PMQR prevalence was highly variable among the enterobacterial species or when the different genes were considered. The prevalent PMQR genes were located in class 1 integrons [qnrB2, qnrB10, and aac(6')-Ib-cr]; in the ColE1-type plasmid pPAB19-1 or Tn2012-like transposons (qnrB19); and in Tn6238 or bracketed by IS26 and bla OXA-1 [aac(6')-Ib-cr]. The mutations associated with quinolone resistance that were located in the quinolone resistance-determining region (QRDR mutations) of gyrA, parC, and gyrB were also investigated. The occurrence of QRDR mutations was significantly associated with the presence of PMQR genes: At least one QRDR mutation was present in 82% of the PMQR-harboring isolates but in only 23% of those without PMQR genes (p < 0.0001, Fisher's Test). To the best of our knowledge, this is the first report on the prevalence of PMQR genes in consecutive clinical enterobacteria where all the genes currently known have been screened.

Fluoroquinolones are highly effective antibiotics with many desirable pharmacokinetic and pharmacodynamic properties including high bioavailability, large volume of distribution, and a broad spectrum of antimicrobial activity. Despite their attractive profile as anti-infective agents, their use in children is limited, primarily due to safety concerns. In this review we highlight the pharmacological properties of fluoroquinolones and describe their current use in pediatrics. In addition, we provide a comprehensive assessment of the safety data associated with fluoroquinolone use in children. Although permanent or destructive arthropathy remains a significant concern, currently available data demonstrate that arthralgia and arthropathy are relatively uncommon in children and resolve following cessation of fluoroquinolone exposure without resulting in long-term sequelae. The concern for safety and risk of adverse events associated with pediatric fluoroquinolone use is likely driving the limited prescribing of this drug class in pediatrics. However, in adults, fluoroquinolones are the most commonly prescribed broad-spectrum antibiotics, resulting in the development of drug-resistant bacteria that can be challenging to treat effectively. The consequence of misuse and overuse of fluoroquinolones leading to drug resistance is a greater, but frequently overlooked, safety concern that applies to both children and adults and one that should be considered at the point of prescribing., Competing Interests: None of the authors has any conflict of interest in regard to this manuscript., (© 2016, The American College of Clinical Pharmacology.)

Quinolones and fluoroquinolones are widely used to treat uropathogenic Escherichia coli infections. Bacterial resistance to these antimicrobials primarily involves mutations in gyrA and parC genes. To date, no studies have examined the potential relationship between biochemical characteristics and quinolone resistance in uropathogenic E. coli strains. The present work analyzed the quinolone sensitivity and biochemical activities of fifty-eight lactose-negative uropathogenic E. coli strains. A high percentage of the isolates (48.3%) was found to be resistant to at least one of the tested quinolones, and DNA sequencing revealed quinolone resistant determining region gyrA and parC mutations in the multi-resistant isolates. Statistical analyses suggested that the lack of ornithine decarboxylase (ODC) activity is correlated with quinolone resistance. Despite the low number of isolates examined, this is the first study correlating these characteristics in lactose-negative E. coli isolates.

Published descriptions of the specific lines of research leading to the discovery of therapeutically important medicines, especially major new class medicines, have long provided value to the biopharmaceutical community as models of success, often influencing the strategies and methods of subsequent drug research. Quinolone antibacterials represent one of medicine's most important classes of anti-infective agents; yet in contrast to many other classes of anti-infectives, astonishingly few details concerning the origin of the class or the rationale leading to the selection of the first clinical agent, nalidixic acid, were ever published by the discoverers. Moreover, earlier disclosures of an independent discovery of the quinolone class of antibacterials have been almost entirely overlooked by the scientific literature. This review brings together all the available information from primary literature sources relating to both discoveries and provides for the first time a much fuller, if still partially speculative, story of the earliest years of this important class of drugs.

Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory infections in adults, who are frequently treated with fluoroquinolones. The aims of this study were to characterize the genotypes of fluoroquinolone-resistant NTHi isolates and their mechanisms of resistance. Among 7,267 H. influenzae isolates collected from adult patients from 2000 to 2013, 28 (0.39%) were ciprofloxacin resistant according to Clinical and Laboratory Standards Institute (CLSI) criteria. In addition, a nalidixic acid screening during 2010 to 2013 detected five (0.23%) isolates that were ciprofloxacin susceptible but nalidixic acid resistant. Sequencing of their quinolone resistance-determining regions and genotyping by pulse-field gel electrophoresis and multilocus sequence typing of the 25 ciprofloxacin-resistant isolates available and all 5 nalidixic acid-resistant isolates were performed. In the NTHi isolates studied, two mutations producing changes in two GyrA residues (Ser84, Asp88) and/or two ParC residues (Ser84, Glu88) were associated with increased fluoroquinolone MICs. Strains with one or two mutations (n = 15) had ciprofloxacin and levofloxacin MICs of 0.12 to 2 μg/ml, while those with three or more mutations (n = 15) had MICs of 4 to 16 μg/ml. Long persistence of fluoroquinolone-resistant strains was observed in three chronic obstructive pulmonary disease patients. High genetic diversity was observed among fluoroquinolone-resistant NTHi isolates. Although fluoroquinolones are commonly used to treat respiratory infections, the proportion of resistant NTHi isolates remains low. The nalidixic acid disk test is useful for detecting the first changes in GyrA or in GyrA plus ParC among fluoroquinolone-susceptible strains that are at a potential risk for the development of resistance under selective pressure by fluoroquinolone treatment., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Unlabelled: In France, according to the National Epidemiology Observatory of Bacterial Resistance to Antibiotics, 15.3% of outpatient urinary Escherichia coli isolates were fluoroquinolone-resistant in 2010. This puts to question the relevance of empirical fluoroquinolone therapy for community-acquired acute pyelonephritis (APN), potentially severe infections., Objectives: We had for aim to identify individual risk factors for quinolone-resistant E. coli in community-acquired APN., Patients and Methods: A retrospective cohort study of 344 adult female patients presenting with E. coli APN was conducted at the Roanne and Saint-Etienne hospital emergency departments, from January 2011 to February 2012. We studied the demographic, administrative, and clinical factors. E. coli strains with intermediate susceptibility on the antibiogram were considered as resistant., Results: There was 23% of isolates that were resistant to nalidixic acid and 17.4% to ofloxacin. Complicated APN was not a significant risk factor (univariate analysis). Three risk factors of resistance to nalidixic acid and ofloxacin were independent (multivariate analysis): fluoroquinolone use in the previous 3 months, hospitalization in the previous 6 months, and stay in a long-term care facility. The resistance to ofloxacin reached 30.6% if at least 1 of these risk factors was present; it was 9% when none of the factors were present., Conclusions: These results suggest that local recommendations for the empirical therapy of APN should be reviewed. The limitations of our study require backing up our results with prospective multicentric studies that could lead to drafting new national recommendations., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: Diarrhea is the leading cause of morbidity and mortality in under-five children in developing countries including Ethiopia. Therefore, up-to-date data on etiologic agent and susceptibility pattern are important for the management of bacterial diarrhea in under-five children, which was the main objective of this study., Method: A cross-sectional study was conducted at Hawassa Adare Hospital and Millennium Health Center from June 6 to October 28, 2011. A total of 158 under-five children with diarrhea were selected using convenient sampling technique. Demographic and clinical data were collected using questionnaire. Fecal samples were collected and processed for bacterial isolation, and antimicrobial susceptibility testing following standard bacteriological techniques., Result: A total of 158 fecal samples were collected from 81(51.3%) males and 77(48.7%) females of under-five children with diarrhea. Of the 158 fecal samples, 35(22.2%) bacterial pathogens were isolated. The isolated bacteria were Campylobacter species, 20 (12.7%), Shigella species, 11 (7.0%), and Salmonella species, 4 (2.5%). The majority of the isolates were sensitive to chloramphenicol, ciprofloxacin, nalidixic acid and cotrimoxazol and high rate of drug resistance was observed against erythromycin and amoxicillin., Conclusions: The finding of this study indicates that Campylobacter species were the predominant etiologies and the presence of bacterial isolates resistant to the commonly prescribed drugs for treating diarrhea in children. Therefore, periodic monitoring of etiologic agent with their drug resistant pattern is essential in the management of diarrhea in children.

Shigellosis, caused by Shigella species, is a major public health problem in Bangladesh. To determine the prevalence and distribution of different Shigella species, we analyzed 10,827 Shigella isolates from patients between 2001 and 2011. S. flexneri was the predominant species isolated throughout the period. However, the prevalence of S. flexneri decreased from 65.7% in 2001 to 47% in 2011, whereas the prevalence of S. sonnei increased from 7.2% in 2001 to 25% in 2011. S. boydii and S. dysenteriae accounted for 17.3% and 7.7% of the isolates respectively throughout the period. Of 200 randomly selected S. sonnei isolates for extensive characterization, biotype g strains were predominant (95%) followed by biotype a (5%). Resistance to commonly used antibiotics including trimethoprim-sulfamethoxazole, nalidixic acid, ciprofloxacin, mecillinam and ampicillin was 89.5%, 86.5%, 17%, 10.5%, and 9.5%, respectively. All isolates were susceptible to ceftriaxone, cefotaxime, ceftazidime and imipenem. Ninety-eight percent of the strains had integrons belonging to class 1, 2 or both. The class 1 integron contained only dfrA5 gene, whereas among class 2 integron, 16% contained dhfrAI-sat1-aadA1-orfX gene cassettes and 84% harbored dhfrA1-sat2 gene cassettes. Plasmids of ∼5, ∼1.8 and ∼1.4 MDa in size were found in 92% of the strains, whereas only 33% of the strains carried the 120 MDa plasmid. PFGE analysis showed that strains having different integron patterns belonged to different clusters. These results show a changing trend in the prevalence of Shigella species with the emergence of multidrug resistant S. sonnei. Although S. flexneri continues to be the predominant species albeit with reduced prevalence, S. sonnei has emerged as the second most prevalent species replacing the earlier dominance by S. boydii and S. dysenteriae in Bangladesh.

Background & Objectives: Salmonella enterica serovars Typhi and Paratyphi are predominantly known to cause enteric fever. Multidrug resistance in S. Tphi and S. Paratyphi has emerged as a cause of concern. This study was done to evaluate status in antimicrobial susceptibility patterns of Salmonella enterica serovar Typhi (S. Typhi) and S. Paratyphi obtained from blood culture in a tertiary care hospital in south India., Methods: Blood isolates of Salmonella species over a two year period between May 2009 and June 2011 were studied. A total of 322 isolates of Salmonella species were tested for antimicrobial susceptibility by Kirby-Bauer disc diffusion method. The MIC of ciprofloxacin was obtained by E-test, and azithromycin MIC was confirmed by agar dilution method for a limited number of isolates., Results: Of the total of 322 isolates studied, 186 (57.8%) were S. Typhi, 134 (41.6%) were S. Paratyphi A, and two were S. Paratyphi B. Of these, 44(13.66%) were resistant to ciprofloxacin (MIC <0.50 μg/ml) and 296 (91.9%) were nalidixic acid resistant. Of these 296 nalidixic acid resistant isolates, 278 (94%) were susceptible to ciprofloxacin by MIC criteria (<0.5 μg/ml). Of the 262 isolates tested for azithromycin sensitivity, only 120 (46%) were susceptible, whereas 81 (31%) were resistant and 55 (21%) showed intermediate susceptibility. Of the isolates, 322 (90%) were susceptible to ampicillin and (95%) were susceptible to co-trimoxazole. However, all the isolates were susceptible to chloramphenicol and ceftriaxone., Interpretation & Conclusions: Nalidixic acid resistance screening is not a reliable surrogate indicator of ciprofloxacin resistance. Ciprofloxacin MIC should to be routinely done. Azithromycin resistance appears to be emerging. However, isolates showed a high degree of susceptibility to ampicillin, co-trimoxazole and chloramphenicol. Thus, antibiotics like ampicillin and co-trimoxazole may once again be useful for the management of enteric fever in southern India.

Food-borne salmonellosis is an important public health problem worldwide and the second leading cause of food-borne illnesses in Hong Kong. In this study, the prevalence and antimicrobial resistance of Salmonella in meat products in Hong Kong were determined. Interestingly, a plasmid-mediated quinolone resistance (PMQR) gene combination, oqxAB, which mediates resistance to nalidixic acid, chloramphenicol, and olaquindox, was for the first time detectable on the chromosomes of two Salmonella enterica serovar Derby isolates. Further surveillance of oqxAB in Salmonella will be needed.

Purpose: The present study was performed to assess the current susceptibility pattern of blood isolates of Salmonella spp from a super specialty hospital in North India against nalidixic acid, ciprofloxacin and azithromycin and compare the in vitro and in vivo response against azithromycin., Materials and Methods: We evaluated the minimum inhibitory concentration's (MIC's) of 107 blood isolates of Salmonella spp against nalidixic acid, azithromycin and ciprofloxacin and correlated in vitro and in vivo response of azithromycin from the treatment and discharge summaries from the Hospital Information System (HIS) software., Results: Among the 107 isolates evaluated, 94 (87.8%) were nalidixic acid-resistant (NAR) Salmonella and 36 were resistant to azithromycin by MIC testing. The MIC 90 value for azithromycin was 24 μg/mL. Among the 57 treatment histories evaluated using the HIS software, 19 (33%) patients had documented clinical non-response to azithromycin which required change of therapy., Conclusions: The present study observed a higher MIC 90 values for azithromycin compared to Salmonella isolates from Western studies. There was also a documented clinical non-response against azithromycin. The in vitro and in vivo findings in this study suggest a guarded use of azithromycin for cases of enteric fever in India. The study also augments the reversal of resistance pattern in favour of chloramphenicol, ampicillin and trimethoprim - sulfamethoxazole.

Objectives: The aim of this study was to define the epidemiological, clinical, and antibiotic susceptibility patterns of Shigella gastroenteritis cases occurring during the years 2003-2009 and to compare results with those of the years 1987-2002., Methods: A hospital-based study was conducted over a 22-year period. All 238 Shigella strains isolated between 2003 and 2009 were compared to 618 isolates from the period 1987-1994 and 218 Shigella strains isolated during 1995-2002 with regard to antimicrobial resistance patterns and patient clinical characteristics., Results: The predominant species during all periods was Shigella sonnei, with an increasing predominance across the periods (64.0%, 71.5%, and 87.8%, respectively; p<0.001). Neither the prevalence of bloody diarrhea nor other clinical characteristics changed across the study periods, except for the prevalence of dehydration, which increased (11.0%, 20.6%, and 28.6%, respectively; p<0.001). During the period 2003-2009, 69.9% of Shigella were resistant to trimethoprim/sulfamethoxazole, 35.8% to ampicillin, and 4.7% to nalidixic acid. No case resistant to ciprofloxacin was detected. Multidrug resistance was also found to be similar in the last two periods (24.0% vs. 28.1%, respectively)., Conclusions: There was both a microbiological and a clinical change in childhood Shigella gastroenteritis cases over the 22 years. The antibiotic resistance pattern appears to have remained stable over the last two periods. There is a need to re-examine the criteria and clinical management guidelines for suspected shigellosis cases., (Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

With an aim to evaluate the isolation rate and antibiotic susceptibility pattern in Salmonella enterica serovar Typhi and S. Paratyphi A, 656 blood samples collected from clinically diagnosed enteric fever patients at National Public Health Laboratory, Nepal during January through December 2008 were processed. Isolates were identified by standard microbiological procedures including serotyping. Antibiotic susceptibility testing was performed by disc diffusion method and minimum inhibitory concentration (MIC) to ciprofloxacin, ofloxacin and nalidixic acid was determined by agar dilution method following CLSI guidelines. Altogether 59 isolates of S. Typhi (49.15%) and S. Paratyphi A (50.85%) were recovered. A total of 80% isolates were resistant to nalidixic acid with S. Paratyphi A (93%) showing significantly higher resistance (P < 0.05) compared to S. Typhi (66%). The nalidixic acid resistant S. Paratyphi A strains required significantly higher MICs (P < 0.001) to quinolone (MIC expressed as mean +/- SD for nalidixic acid 477.87 +/- 87.02 microg/mL, ofloxacin 1.8 +/- 0.63 microg/mL, ciprofloxacin 0.62 +/- 0.3 microg/mL) compared with that of S. Typhi (nalidixic acid 173.18 +/- 72.03 microg/mL, ofloxacin 0.43 +/- 0.11 microg/mL, ciprofloxacin 0.25 microg/mL). Increased MIC of fluoroquinolone (FQ) is of particular concern in emerging strains of S. Paratyphi A as exposure to these drugs fuels up further development of full FQ resistant populations. Use of FQs as the first-line drugs for empirical therapy and management of enteric fever in areas where these strains are prevalent is questionable and requires an urgent review.

Owing to multidrug resistance, quinolones and third-generation cephalosporins are currently used as key antibiotics to combat Salmonella organisms. Therapy failure due to reduced ciprofloxacin susceptibility has been reported in endemic areas, but also in imported disease. Different bacterial resistance mechanisms may result in reduced ciprofloxacin susceptibility. In this study, the presence and expression of different resistance mechanisms resulting in reduced minimum inhibitory concentrations (MICs) for ciprofloxacin were evaluated in 23 blood-culture-derived Salmonella enterica serotypes Typhi and Paratyphi A organisms from ill-returned travellers to Asia. The presence of mutations in the quinolone resistance-determining region (QRDR) of the gyrA gene as well as an activated efflux pump and plasmid-mediated quinolone resistance genes was determined. Resistance selection during therapy and the clonal relatedness of all isolates were established. Efflux pump inhibition did not appear to affect the MICs of ciprofloxacin and activity of the efflux pump appeared to be specific for nalidixic acid. Repeated exposure of the isolates to ciprofloxacin did not result in a significant increase in the MICs for ciprofloxacin. Repetitive sequence-based polymerase chain reaction (rep-PCR) profiles identified five different genotypes, but no correlation with resistance was observed. However, a significant relation was found with geographic region; reduced ciprofloxacin susceptibility was only found in travellers returning from India and Pakistan. All isolates with reduced ciprofloxacin susceptibility had a mutation at position 83 in the QRDR region of the gyrA gene. Plasmid-mediated quinolone resistance was not found. These findings confirm that the reduced ciprofloxacin MIC in S. Typhi and S. Paratyphi A is solely due to an amino acid substitution in the QRDR 'cluster' of the gyrA gene., (Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Nontyphoidal salmonellae (NTS) are important causes of community-acquired bloodstream infection. We describe patterns of antimicrobial resistance among invasive NTS in the United States. We compared bloodstream NTS isolates with those from stool submitted to the National Antimicrobial Resistance Monitoring System (NARMS) from 1996 to 2007. We describe antimicrobial resistance among invasive strains by serogroup and serotype. Of the 19,302 NTS isolates, 17,804 (92.2%) were from stool or blood. Of these, 1,050 (5.9%) were bloodstream isolates. The median ages (ranges) of patients with and without bacteremia were 36 (<1 to 97) years and 20 (<1 to 105) years, respectively (P < 0.001). Males (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.06 to 1.38) and those ≥65 years of age were at greater risk for invasive disease. Salmonella enterica serotypes Enteritidis, Typhimurium, and Heidelberg were the most common serotypes isolated from blood; S. enterica serotypes Dublin, Sandiego, and Schwarzengrund were associated with the greatest risk for bloodstream isolation. Of invasive isolates, 208 (19.8%) were resistant to ampicillin, 117 (11.1%) to chloramphenicol, and 26 (2.5%) to trimethoprim-sulfamethoxazole; 28 (2.7%) isolates were resistant to nalidixic acid and 26 (2.5%) to ceftriaxone. Antimicrobial resistance to traditional agents is common. However, the occurrence of nalidixic acid and ceftriaxone resistance among invasive NTS is cause for clinical and public health vigilance.

Poly(2-(dimethylaminoethyl) methacrylate) (pDMAEMA) was grafted to low density polyethylene (LDPE) and silicone rubber (SR) in order to make them less susceptible to microbial biofilm formation. The direct grafting of DMAEMA using γ-rays was an efficient and fast procedure for obtaining modified materials, which could be quaternized in a second step using methyl iodide. Raman spectroscopy showed that the grafting occurred only at the surface of the LDPE, but both at the surface and in the bulk of the SR. Consequently, the grafted chains caused changes in the surface-related features of the LDPE (water contact angle and viscoelastic behavior in the dry state) and in the bulk-related properties of the SR (swelling and viscoelasticity in the swollen state). The microbiological assays revealed that the grafted DMAEMA reduced Candida albicans biofilm formation (almost no biofilm on SR), while the quaternized surfaces inhibited C. albicans and Staphylococcus aureus biofilm by more than 99% compared to pristine materials. Modified LDPE and SR were capable of holding considerable amounts of nalidixic acid, an anionic antimicrobial drug, and sustained the release for several hours. In addition, the grafted materials were cytocompatible (fibroblast cell survival > 70%). In conclusion, these materials have the ability to inhibit microbial biofilm formation and at the same time act as drug-eluting systems, and for that reason may hold great promise for anti-biofouling applications.

Introduction: Chronic dacryocystitis results in chronic infection and inflammation of the lacrimal sac., Objective: To identify the aetiology of chronic dacryocystitis and to determine their antimicrobial susceptibility pattern., Materials and Methods: A cross - sectional study was undertaken including 120 lacrimal swab materials collected from patients aged above 15 years suffering from chronic dacryocystitis., Statistics: Data analysis was done by using software "Win pepi'' ver 7.9., Results: The bacteria of eight different species were isolated from 76.66 % (92/120) culture positive samples. 85.86 % showed a single and 14.13 % showed a mixed growth pattern. Coagulase negative staphylococci were the most common bacteria (P= 0.018) accounting for 33.96 % followed by Staphylococcus aureus (25.46 %), Streptococcus pneumoniae ( 19.81 % ), Streptococci viridans (5.66 %), Escherichia coli (5.66 %), Haemophilus spp ( 4.71 % ), Streptococcus pyogenes (3.77 %) and Bacillus spp (0.94 % ). Staphylococcus aureus were the most predominant bacteria in mixed growth. Rate of infection was higher in males 81.39 % than in females 74.02 %. Infection was higher in the age group of above 31 years. In the antimicrobial susceptibility test, except staphylococcus aureus, all the Gram positive isolates were 100 % sensitive to chloramphenicol and were least sensitive to tobramycin, but Gram negative isolates were equally sensitive to Chloramphenicol and Nalidixic acid., Conclusion: Coagulase negative staphylococci are the most frequently isolated bacteria. Staphylococcus aureus is predominantly found in mixed growth. Chloramphenicol is the most effective drug of choice for chronic dacryocystitis., (© Nepal Ophthalmic Society.)

Enteric fever is a global health problem and there is emerging drug resistance with some reports of re-emerging sensitivity to previously used antibiotics eg, chloramphenicol. This study was done to compare the drug sensitivity pattern of enteric fever over a decade period. Twenty-five culture positive patients for S typhi from one study done between October 1993 to February 1995 and 35 positive patients from another study done between September 2005 and August 2006 in the same hospital were taken into account and their sensitivity pattern was compared. A total of 36% of cases were sensitive to all the drugs and equal number were multidrug resistant in the study in 1995, while in 2006 only 14.2% (p<0.05) were sensitive to all drugs and percentage of multidrug resistance has increased to 42% (p>0.05). Sensitivity to chloramphenicol had decreased from 68.00% to 54.30% (p>0.05). With the emergence of resistant strains there is significant decline in overall sensitivity to all first line drugs. However there is no change in chloramphenicol sensitivity of Salmonella enterica serovar typhi 10 years back and now, this alone is not the sufficient reason for reintroduction of this drug especially in younger patients.

Nalidixic acid-resistant Salmonella typhi NARST infections increase minimal inhibitory concentrations of fluoroquinolones, due to chromosomal mutations in the gene encoding DNA gyrase, and can lead to a delayed treatment response. This in turn alters the course of the disease allowing for a protracted period of illness and the occurrence of complications. In this case report, we present a patient from the Indian sub-continent, who was diagnosed with NARST complicated by sub-intestinal obstruction, her diagnosis, treatment, and subsequent recovery.

Objective: To find out the frequency of low-level quinolone-resistance in Multi-Drug Resistant (MDR) typhoid using nalidixic acid screening disc., Study Design: Descriptive study., Place and Duration of Study: Armed Forces Institute of Pathology, Rawalpindi, from January 2005 to December 2005., Materials and Methods: Blood was obtained from suspected cases of typhoid fever and cultured in to BacT/ALERT. The positive blood cultures bottles were subcultured. The isolates were identified by colony morphology and biochemical tests using API-20E galleries. Susceptibility testing of isolates was done by modified Kirby-Bauer disc diffusion method on Muellar Hinton Agar. For the isolates, which were resistant to nalidixic acid by disc diffusion method, Minimal Inhibitory Concentrations (MICs) of ciprofloxacin and nalidixic acid were determined by using the E-test strips. Disc diffusion susceptibility tests and MICs were interpreted according to the guidelines provided by National Committee for Control Laboratory Standard (NCCLS)., Results: A total of 21(65.5%) out of 32 isolates of Salmonellae were nalidixic acid-resistant by disk diffusion method. All the nalidixic acid-resistant isolates by disc diffusion method were confirmed by MICs for both ciprofloxacin and nalidixic acid. All the nalidixic acid-resistant isolates had a ciprofloxacin MIC of 0.25-1microg/ml (reduced susceptibility) and nalidixic acid MICs > or = 32 microg (resistant). Out of all Salmonella isolates, 24 (75%) were found to be MDR, and all were S. typhi., Conclusion: Low-level quinolone-resistance in typhoid was high in this small series. Screening for nalidixic acid resistance with a 30 microg nalidixic acid disk is a reliable and cost-effective method to detect low-level fluoroquinolone resistance, especially in the developing countries.

Unlabelled: The last two decades have seen a change in the pattern of enteric fever with the emergence of multidrug-resistant strains (MDRS), particularly strains resistant to nalidixic acid., Aim: The aim of the study was to undertake a retrospective analysis of blood culture-confirmed cases of enteric fever diagnosed at Safdarjang Hospital, New Delhi, India from January 2001 to December 2003., Methods: The epidemiological details, clinical features, treatment outcome and antimicrobial resistance patterns were studied., Results: Of 377 blood culture-positive cases, 80.6% were Salmonella typhi and 19.4% Salmonella paratyphi A; 21.7% were children aged under 5 years and 6.1% were under 2 years. A significant decline in MDRS was observed, from 21.9% in 2001 to 12.4% in 2003 (p=0.04). There was a significant increase in nalidixic acid-resistant Salmonella (NARS) from 56.9% in 2001 to 88.9% in 2003 (p=0.0001). Complete resistance to ciprofloxacin (MIC>4 microg/ml) was detected in only two isolates, both Salmonella paratyphi A. Minimal inhibitory concentrations (MICs) of ciprofloxacin for NARS were increased (0.125-0.5 microg/ml) but were within National Committee for Clinical Laboratory Standards susceptibility ranges. NARS had a significantly longer fever defervescence time (7.7 vs 4.7 days, p<0.001) and hospital stay (12.1 vs 8.2 days, p<0.001), and higher rates of complications (55.5% vs 24.0%, p=0.014) and mortality than nalidixic acid-sensitive Salmonella (NASS). The rate of isolation of MDRS was higher in NARS than NASS (18.8% vs 7.3%, p=0.013)., Conclusion: The high rate of occurrence of enteric fever in children <5 years and also of infections caused by Salmonella paratyphi A in India calls for critical re-assessment of vaccination strategy. Nalidixic acid resistance and rising MICs of fluoroquinolones in Salmonella spp pose a new global threat requiring debate on the optimum treatment of enteric fever.

Background: This study was carried out to estimate the frequency of urinary tract infection among children subjected to urine culture presenting to Sam Hospital, Sana'a city, Yemen and to determine the susceptibility of the isolated bacteria to the antibiotics., Methods: Record-based study was done in Sam hospital in Sana'a city Yemen during three years 1/1/1999-31/12/2001. Out of 70,500 patients seen for different causes through that period 820 (1.16%) having urinary symptoms (fever, rigor, vomiting, frequency or screams during the act of urination) were subjected to urine culture. Data about age and sex were also collected., Results: Frequency of urinary tract infections among children examined by urine culture was 36.8% (n=302), with mean age of 7.6 years. 272 (90.1%) of them were females, and 30 (9.9%) were males. More than half 154 (51%) of infected patients were less than three years old. The isolated bacteria was Escherichia coli 201 (66.3%) followed by Staphylococcus suprofyticus 45 (14.9%), Proteus spp 15 (4.9%), Klebsiella 12 (3.9%) then Enterococcus spp 12 (3.9%). Sensitivity of E. coli to Nalidexic acid was 70%, to Amoxicillin/Clavulanic acid was 29.9%, to Co-trimoxasole was 16.4%, and to Nitrofurantoin was 15.9%., Conclusion: The majority of the infected patients were females and the highest frequency of the disease was in the first three years of age. The most common isolated microorganism was E. coli followed by Staphylococcus suprofyticus, Proteus spp, then Enterococcus spp. The highly active antibiotic for most organisms isolated was Nalidexic acid, then amoxicillin/clavulanic acid. Nalidexic acid can be used as a first line empiric treatment and/or prophylaxis of UTI in children.

Among shigellas isolated from patients in England and Wales in 2002, 10% of subgroups A, B and C, and 13% of subgroup D (Shigella sonnei), were resistant to nalidixic acid. As a consequence, should antimicrobial therapy be indicated, the efficacy of nalidixic acid as the preferred treatment for children with bacillary dysentery has been jeopardised.

Background: Non-typhoidal Salmonella are one of the key etiological agents of diarrhoeal disease. The appearance of multiple drug resistance along with resistance to quinolones in this bacterium poses a serious therapeutic problem. We determined the prevalence of nalidixic acid and ciprofloxacin resistance in non-typhoidal Salmonella isolated from faecal samples of patients with acute diarrhoeal disease attending the outpatient and inpatient department of a hospital in Saudi Arabia during the years 1999 to 2002., Methods: Non-typhoidal Salmonella were isolated from faecal samples. Antimicrobial susceptibility was tested by the disc diffusion test. MICs to nalidixic acid and ciprofloxacin were determined by the agar dilution method., Results: During the study period, 524 strains of non-typhoidal Salmonella were isolated. Strains belonging to serogroup C1 were the commonest (41.4%) followed by serogroups B and D (15.6% and 14.5%, respectively). Resistance to ampicillin was observed in 22.9% and to trimethoprim/sulfamethoxazole in 18.5% of the strains. Nalidixic acid resistance was encountered in 9.9% and ciprofloxacin resistance in 2.3% of the strains. Resistance to nalidixic acid significantly increased from 0.1% in 1999 to 5.5% in 2002 (P=0.0007) and ciprofloxacin resistance increased significantly from 0.1% in 1999 to 0.9% in 2002 (P=0.0001). MICs to nalidixic acid and ciprofloxacin were determined among 29 nalidixic acid-resistant strains of non-typhoidal Salmonella isolated during 2002. The MIC was >256 microg/mL to nalidixic acid and 8 to 16 microg/mL to ciprofloxacin., Conclusion: The increasing rates of antimicrobial resistance encountered among non-typhoidal Salmonella necessitate the judicious use of these drugs in humans. Moreover, these findings support the concern that the use of quinolones in animal feed may lead to an increase in resistance and should be restricted.

Multidrug-resistant (MDR) Salmonella Typhi (resistant to chloramphenicol, ampicillin, and trimethoprim-sulphamethoxazole) and isolates with reduced susceptibility to fluoroquinolones (indicated by resistance to nalidixic acid, NaR) have caused epidemics and become endemic in southern Viet Nam during the 1990s. Short courses of ofloxacin have proved acceptable for treating MDR/NaS isolates of S. Typhi (ofloxacin MIC90 = 0.06 mg/l) causing uncomplicated disease. Ofloxacin (10-15 mg/kg/d) given for 2, 3, or 5 d cured >90% of patients with an average fever clearance time (FCT) of 4 d. Less than 3% of patients relapsed or had a positive post-treatment stool culture. In contrast, the response of NaR isolates (ofloxacin MIC90 = 0.5 mg/l) to such regimens is poor. For example, ofloxacin (20 mg/kg/d) given for 7 d cured only 75% of patients, with an FCT of 7 d, and 19% of patients had positive post-treatment faecal cultures. Currently available alternatives for NaR infections include ceftriaxone, cefixime, and azithromycin. These antimicrobials are reasonably effective but expensive. New, effective, and affordable regimens are needed to treat these NaR infections. Short courses of the new generation fluoroquinolones or combinations of the available antimicrobials are possible options.

Background: Non-typhoidal Salmonella are one of the key etiological agents of diarrhoeal disease. The appearance of multiple drug resistance along with resistance to quinolones in this bacterium poses a serious therapeutic problem. We determined the prevalence of nalidixic acid and ciprofloxacin resistance in non-typhoidal Salmonella isolated from faecal samples of patients with acute diarrhoeal disease attending the outpatient and inpatient departments of a hospital in Saudi Arabia during the years 1999 to 2002., Methods: Non-typhoidal Salmonella were isolated from faecal samples. Antimicrobial susceptibility was tested by the disc diffusion test. MICs to nalidixic acid and ciprofloxacin were determined by the agar dilution method., Results: During the study period, 524 strains of non-typhoidal Salmonella were isolated. Strains belonging to serogroup C1 were the commonest (41.4%) followed by serogroups B and D (15.6% and 14.5%, respectively). Resistance to ampicillin was observed in 22.9% and to trimethoprim/sulfamethoxazole in 18.5% of the strains. Nalidixic acid resistance was encountered in 9.9% and ciprofloxacin resistance in 2.3% of the strains. Resistance to nalidixic acid significantly increased from 0.1% in 1999 to 5.5% in 2002 (P=0.0007) and ciprofloxacin resistance increased significantly from 0.1% in 1999 to 0.9% in 2002 (P=0.0001). MICs to nalidixic acid and ciprofloxacin were determined among 29 nalidixic acid-resistant strains of non-typhoidal Salmonella isolated during 2002. The MIC was >256 microg/mL to nalidixic acid and 8 to 16 microg/mL to ciprofloxacin., Conclusion: The increasing rates of antimicrobial resistance encountered among non-typhoidal Salmonella necessitate the judicious use of these drugs in humans. Moreover, these findings support the concern that the use of quinolones in animal feed may lead to an increase in resistance and should be restricted.

The ECO.SENS study investigated the prevalence and antimicrobial susceptibility of pathogens causing community-acquired acute uncomplicated urinary tract infections (UTIs) in 4734 women aged 18-65 years presenting with symptoms of acute UTI, at 252 community healthcare centres in 16 countries in Europe plus Canada. Resistance in Escherichia coli occurred most frequently to ampicillin (30%) and sulphonamides (29%), followed by trimethoprim (15%), trimethoprim/sulphamethoxazole (14%) and nalidixic acid (5%) but was low to co-amoxiclav, mecillinam, cefadroxil, nitrofurantoin, fosfomycin, gentamicin and ciprofloxacin, all at<3%. Consumption of antibiotics in 1997 varied more than 4-fold within Europe and from 9 to 37 DDD/1000 inhabitants/day, the consumption being highest in Southern Europe. The consumption of broad-spectrum penicillins correlated with resistance to ampicillin and there was a clear correlation between quinolone consumption and resistance to ciprofloxacin and nalidixic acid. The 4-fold difference in antibiotic consumption within Europe and the correlation to resistance emphasises the importance of controlling antibiotic usage.

Salmonella enterica infections cause considerable morbidity and mortality worldwide. Antimicrobial therapy may be life-saving for patients with extraintestinal infections with S. enterica serotype Typhi or non-Typhi salmonellae. Because antimicrobial resistance to several classes of traditional first-line drugs has emerged in the past several decades, the quinolone antimicrobial agents, particularly the fluoroquinolones, have become the drugs of choice. Recently, resistance to nalidixic acid has emerged among both Typhi and non-Typhi Salmonella serotypes. Such Salmonella isolates typically also have decreased susceptibility to fluoroquinolones, although minimum inhibitory concentrations of the fluoroquinolones usually are within the susceptible range of the interpretive criteria of the NCCLS. A growing body of clinical and microbiological evidence indicates that such nalidixic acid-resistant S. enterica infections also exhibit a decreased clinical response to fluoroquinolones. In this article, we recommend that laboratories test extraintestinal Salmonella isolates for nalidixic acid resistance, we recommend that short-course fluoroquinolone therapy be avoided for infection with nalidixic acid-resistant extraintestinal salmonellae, and we summarize existing data and data needs that would contribute to reevaluation of the current NCCLS fluoroquinolone breakpoints for salmonellae.

Objective: To study the drug sensitivity pattern of cholera in children., Setting: DTU of Civil Hospital, Karachi., Patients and Methods: All children age 2 months to 15 years attending Diarrhoea Treatment Unit (DTU) with acute onset of diarrhoea and dehydration were screened for cholera. Stool samples were collected in alkaline peptone and those positive for cholera had their antibiotic sensitivity determined., Results: Of 846 stool specimens, 161 were positive for V. Cholera. All were sensitive to third generation cephalosporins and quinolones, 98-100% to nalidixic acid, 82-86% to chloramphenicol and 67-75% to doxycycline and all were resistant to cotrimaxazole., Conclusion: Cholera can be treated with nalidixic acid or chloramphenical in young children while doxycycline for older children. Cotrimoxazole is not effective. Efforts should be done for identification and surveillance of cholera cases, along with change of sensitivity pattern of Vibrio cholera.

Shigellosis has been a major cause of dysentery for many years at Vellore, south India. In the last two years the number of Shigella being isolated from samples of faeces from patients with diarrhoea has decreased (5% isolation rate in 1997 to 3.9% in 2001), although the microbiological methods and media used have not changed. Also, the nalidixic acid (NA) resistance has increased for S. sonnei (now 94%). This is noteworthy, since NA has been recommended for the empirical treatment of patients suspected to have shigellosis and this concept needs to be reconsidered based on available data.