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1.
J Nepal Health Res Counc ; 20(2): 517-523, 2022 Nov 03.
Article in English | MEDLINE | ID: mdl-36550738

ABSTRACT

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.


Subject(s)
Typhoid Fever , Humans , Typhoid Fever/drug therapy , Salmonella typhi/genetics , Fluoroquinolones/pharmacology , Fluoroquinolones/therapeutic use , Nalidixic Acid/pharmacology , Nalidixic Acid/therapeutic use , Drug Resistance, Bacterial/genetics , Nepal , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbial Sensitivity Tests , Mutation
2.
J Infect Dev Ctries ; 15(4): 579-583, 2021 04 30.
Article in English | MEDLINE | ID: mdl-33956660

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Resistance, Multiple, Bacterial/drug effects , Fluoroquinolones/therapeutic use , Nalidixic Acid/therapeutic use , Typhoid Fever/microbiology , Anti-Bacterial Agents/pharmacology , Fluoroquinolones/pharmacology , Humans , India , Microbial Sensitivity Tests , Nalidixic Acid/pharmacology , Salmonella paratyphi A/isolation & purification , Typhoid Fever/drug therapy
3.
Proc Natl Acad Sci U S A ; 118(13)2021 03 30.
Article in English | MEDLINE | ID: mdl-33766914

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Drug Resistance, Bacterial/genetics , Drug Therapy, Combination , Epidemics , Evolution, Molecular , Adaptation, Physiological , Anti-Bacterial Agents/pharmacology , Bacterial Infections/microbiology , Computer Simulation , Escherichia coli/drug effects , Escherichia coli/genetics , Humans , Mutation , Nalidixic Acid/pharmacology , Nalidixic Acid/therapeutic use , Patient Admission , Patient Discharge , Streptomycin/pharmacology , Streptomycin/therapeutic use
4.
Int J Antimicrob Agents ; 55(5): 105909, 2020 May.
Article in English | MEDLINE | ID: mdl-31991220

ABSTRACT

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 ß-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.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Cephalosporins/therapeutic use , Ciprofloxacin/therapeutic use , Drug Resistance, Bacterial/genetics , Escherichia coli/drug effects , Nalidixic Acid/therapeutic use , Escherichia coli/genetics , Escherichia coli/isolation & purification , Escherichia coli Infections/drug therapy , Escherichia coli Infections/epidemiology , France/epidemiology , Humans , Microbial Sensitivity Tests , Outpatients/statistics & numerical data , Prevalence , Retrospective Studies , beta-Lactamases/genetics
5.
J Dermatol Sci ; 92(2): 188-196, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30219520

ABSTRACT

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 ß-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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antrodia/chemistry , Dermatitis, Atopic/drug therapy , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Skin Infections/drug therapy , Toluene/analogs & derivatives , Toluene/pharmacology , Administration, Cutaneous , Animals , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/therapeutic use , Cell Line , Chemokines/immunology , Chemokines/metabolism , Dermatitis, Atopic/immunology , Dermatitis, Atopic/microbiology , Disease Models, Animal , Drug Evaluation, Preclinical , Filaggrin Proteins , Humans , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Methicillin-Resistant Staphylococcus aureus/metabolism , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Nalidixic Acid/pharmacology , Nalidixic Acid/therapeutic use , Ovalbumin/immunology , Skin/drug effects , Skin/immunology , Skin/metabolism , Skin/microbiology , Staphylococcal Skin Infections/immunology , Staphylococcal Skin Infections/microbiology , Swine , Toluene/isolation & purification , Toluene/therapeutic use , Treatment Outcome , Water Loss, Insensible/drug effects
6.
Cell Mol Biol (Noisy-le-grand) ; 64(7): 75-79, 2018 May 30.
Article in English | MEDLINE | ID: mdl-29974849

ABSTRACT

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.


Subject(s)
Drug Resistance, Multiple, Bacterial/genetics , Intensive Care Units , Klebsiella Infections/enzymology , Klebsiella pneumoniae/genetics , beta-Lactamases/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Clavulanic Acid/therapeutic use , Cross-Sectional Studies , Female , Humans , Imipenem/therapeutic use , Iran/epidemiology , Klebsiella Infections/drug therapy , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/isolation & purification , Male , Microbial Sensitivity Tests , Middle Aged , Molecular Epidemiology , Nalidixic Acid/therapeutic use , Tertiary Care Centers , beta-Lactamase Inhibitors/therapeutic use
7.
Indian J Med Microbiol ; 36(1): 131-135, 2018.
Article in English | MEDLINE | ID: mdl-29735844

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/therapeutic use , DNA Gyrase/genetics , DNA Topoisomerase IV/genetics , Drug Resistance, Bacterial/genetics , Escherichia coli/drug effects , Escherichia coli/genetics , Fluoroquinolones/therapeutic use , Nalidixic Acid/therapeutic use , Escherichia coli/isolation & purification , Escherichia coli Infections/drug therapy , Escherichia coli Infections/microbiology , Humans , India , Microbial Sensitivity Tests , Tertiary Care Centers
8.
Trop Doct ; 48(3): 182-188, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29495943

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic use , Drug Resistance, Multiple, Bacterial , Nalidixic Acid/therapeutic use , Salmonella typhi/drug effects , Typhoid Fever/drug therapy , Adult , Azithromycin/therapeutic use , Ciprofloxacin/therapeutic use , Cohort Studies , Female , Fluoroquinolones/therapeutic use , Gatifloxacin , Hospitalization , Humans , India/epidemiology , Male , Microbial Sensitivity Tests , Recurrence , Treatment Outcome , Typhoid Fever/epidemiology , Typhoid Fever/microbiology , Young Adult
9.
Eur J Clin Microbiol Infect Dis ; 37(2): 271-276, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29076047

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Ciprofloxacin/therapeutic use , Community-Acquired Infections/drug therapy , Drug Resistance, Multiple, Bacterial/drug effects , Escherichia coli Infections/drug therapy , Escherichia coli/drug effects , Nalidixic Acid/therapeutic use , Tetracycline/therapeutic use , Adult , Community-Acquired Infections/microbiology , Escherichia coli/isolation & purification , Escherichia coli Infections/microbiology , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Retrospective Studies
10.
Indian J Med Res ; 146(Supplement): S53-S58, 2017 Jul.
Article in English | MEDLINE | ID: mdl-29205196

ABSTRACT

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.


Subject(s)
Aeromonas/drug effects , Cholera/drug therapy , Diarrhea/drug therapy , Drug Resistance, Microbial/genetics , Adolescent , Adult , Aeromonas/genetics , Aeromonas/pathogenicity , Cefotaxime/therapeutic use , Child , Child, Preschool , Cholera/epidemiology , Cholera/genetics , Cholera/microbiology , Ciprofloxacin/therapeutic use , Diarrhea/epidemiology , Diarrhea/genetics , Diarrhea/microbiology , Female , Humans , India/epidemiology , Infant , Male , Microbial Sensitivity Tests , Middle Aged , Nalidixic Acid/therapeutic use , Retrospective Studies , Tertiary Care Centers , Young Adult
11.
Am J Trop Med Hyg ; 97(6): 1706-1709, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29016327

ABSTRACT

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.


Subject(s)
Bacteremia/epidemiology , Paratyphoid Fever/epidemiology , Salmonella paratyphi A/drug effects , Typhoid Fever/epidemiology , Ampicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Ceftriaxone/therapeutic use , Chloramphenicol , Drug Resistance, Multiple, Bacterial , Humans , Male , Microbial Sensitivity Tests , Molecular Epidemiology , Nalidixic Acid/therapeutic use , Nepal/epidemiology , Paratyphoid Fever/drug therapy , RNA, Bacterial/isolation & purification , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Typhoid Fever/drug therapy , Young Adult
13.
Microb Drug Resist ; 23(2): 177-187, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27728774

ABSTRACT

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 blaOXA-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.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial/genetics , Enterobacteriaceae/drug effects , Enterobacteriaceae/genetics , Plasmids/genetics , Quinolones/therapeutic use , Argentina , Bacterial Proteins/genetics , Ciprofloxacin/therapeutic use , Enterobacteriaceae Infections/drug therapy , Humans , Integrons/genetics , Microbial Sensitivity Tests/methods , Mutation/genetics , Nalidixic Acid/therapeutic use , Prevalence
14.
J Clin Pharmacol ; 56(9): 1060-75, 2016 09.
Article in English | MEDLINE | ID: mdl-26865283

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/adverse effects , Fluoroquinolones/adverse effects , Gastrointestinal Diseases/chemically induced , Age Factors , Animals , Anti-Bacterial Agents/therapeutic use , Child , Clinical Trials as Topic/methods , DNA Gyrase/metabolism , Drug Resistance, Bacterial/drug effects , Drug Resistance, Bacterial/physiology , Fluoroquinolones/therapeutic use , Gastrointestinal Diseases/diagnosis , Humans , Nalidixic Acid/adverse effects , Nalidixic Acid/therapeutic use , Prospective Studies , Retrospective Studies , Topoisomerase II Inhibitors/adverse effects , Topoisomerase II Inhibitors/therapeutic use
15.
Braz J Microbiol ; 46(3): 753-7, 2015.
Article in English | MEDLINE | ID: mdl-26413057

ABSTRACT

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.


Subject(s)
Drug Resistance, Multiple, Bacterial/genetics , Escherichia coli Infections/drug therapy , Fluoroquinolones/therapeutic use , Lactose/metabolism , Nalidixic Acid/therapeutic use , Ornithine Decarboxylase/genetics , Urinary Tract Infections/drug therapy , Uropathogenic Escherichia coli/genetics , Anti-Bacterial Agents/therapeutic use , Brazil , DNA Gyrase/genetics , DNA Topoisomerase IV/genetics , Decarboxylation/genetics , Decarboxylation/physiology , Escherichia coli Infections/microbiology , Humans , Microbial Sensitivity Tests , Ornithine/metabolism , Urinary Tract Infections/microbiology , Uropathogenic Escherichia coli/drug effects , Uropathogenic Escherichia coli/enzymology , Uropathogenic Escherichia coli/isolation & purification
16.
Braz. j. microbiol ; 46(3): 753-757, July-Sept. 2015. tab, ilus
Article in English | LILACS | ID: lil-755797

ABSTRACT

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.

.


Subject(s)
Humans , Drug Resistance, Multiple, Bacterial/genetics , Escherichia coli Infections/drug therapy , Fluoroquinolones/therapeutic use , Lactose/metabolism , Nalidixic Acid/therapeutic use , Ornithine Decarboxylase/genetics , Urinary Tract Infections/drug therapy , Uropathogenic Escherichia coli/genetics , Anti-Bacterial Agents/therapeutic use , Brazil , DNA Gyrase/genetics , DNA Topoisomerase IV/genetics , Decarboxylation/genetics , Decarboxylation/physiology , Escherichia coli Infections/microbiology , Microbial Sensitivity Tests , Ornithine/metabolism , Urinary Tract Infections/microbiology , Uropathogenic Escherichia coli/drug effects , Uropathogenic Escherichia coli/enzymology , Uropathogenic Escherichia coli/isolation & purification
17.
J Med Chem ; 58(12): 4874-82, 2015 Jun 25.
Article in English | MEDLINE | ID: mdl-25738967

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/history , Bacteria/drug effects , Bacterial Infections/drug therapy , Drug Discovery/history , Quinolones/chemistry , Quinolones/history , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/history , Drug Discovery/methods , History, 20th Century , History, 21st Century , Humans , Nalidixic Acid/chemistry , Nalidixic Acid/history , Nalidixic Acid/pharmacology , Nalidixic Acid/therapeutic use , Quinolones/pharmacology , Quinolones/therapeutic use
18.
Antimicrob Agents Chemother ; 59(1): 461-6, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25385097

ABSTRACT

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.


Subject(s)
Drug Resistance, Bacterial/genetics , Fluoroquinolones/therapeutic use , Haemophilus Infections/drug therapy , Haemophilus influenzae/genetics , Respiratory Tract Infections/drug therapy , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Bacterial Typing Techniques , Base Sequence , Ciprofloxacin/therapeutic use , DNA Gyrase/genetics , DNA Topoisomerase IV/genetics , DNA, Bacterial/genetics , Female , Genetic Variation , Haemophilus Infections/microbiology , Haemophilus influenzae/drug effects , Haemophilus influenzae/isolation & purification , Humans , Levofloxacin/therapeutic use , Male , Microbial Sensitivity Tests , Middle Aged , Multilocus Sequence Typing , Nalidixic Acid/therapeutic use , Pulmonary Disease, Chronic Obstructive/microbiology , Respiratory Tract Infections/microbiology , Sequence Analysis, DNA
19.
Ethiop J Health Sci ; 24(2): 101-8, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24795510

ABSTRACT

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.


Subject(s)
Bacterial Infections/epidemiology , Campylobacter/pathogenicity , Diarrhea/epidemiology , Diarrhea/microbiology , Salmonella/pathogenicity , Shigella/pathogenicity , Amoxicillin/therapeutic use , Ampicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Campylobacter/drug effects , Ceftriaxone/therapeutic use , Child, Preschool , Chloramphenicol/therapeutic use , Cross-Sectional Studies , Developing Countries , Diarrhea/drug therapy , Drug Resistance, Bacterial , Erythromycin/therapeutic use , Ethiopia/epidemiology , Female , Humans , Infant , Infant, Newborn , Male , Nalidixic Acid/therapeutic use , Prevalence , Salmonella/drug effects , Shigella/drug effects , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use
20.
Med Mal Infect ; 44(5): 206-16, 2014 May.
Article in English | MEDLINE | ID: mdl-24794820

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Community-Acquired Infections/drug therapy , Drug Resistance, Multiple, Bacterial , Escherichia coli Infections/drug therapy , Escherichia coli/drug effects , Fluoroquinolones/pharmacology , Pyelonephritis/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Catchment Area, Health , Cohort Studies , Community-Acquired Infections/epidemiology , Community-Acquired Infections/microbiology , Comorbidity , Emergency Service, Hospital/statistics & numerical data , Escherichia coli/isolation & purification , Escherichia coli Infections/epidemiology , Female , Fluoroquinolones/therapeutic use , France/epidemiology , Hospitalization , Hospitals, Teaching/statistics & numerical data , Hospitals, Urban/statistics & numerical data , Humans , Institutionalization , Long-Term Care , Middle Aged , Nalidixic Acid/pharmacology , Nalidixic Acid/therapeutic use , Ofloxacin/pharmacology , Ofloxacin/therapeutic use , Pyelonephritis/epidemiology , Pyelonephritis/microbiology , Retrospective Studies , Risk Factors , Young Adult
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