Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-18 (of 18 Records) |
Query Trace: Sjolund-Karlsson M [original query] |
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Molecular Epidemiology of Carbapenem-Resistant Acinetobacter baumannii in the United States, 2013-2017.
McKay SL , Vlachos N , Daniels JB , Albrecht VS , Stevens VA , Rasheed JK , Johnson JK , Lutgring JD , Sjölund-Karlsson M , Halpin AL . Microb Drug Resist 2022 28 (6) 645-653 Healthcare-associated carbapenem-resistant Acinetobacter baumannii (CRAB) infections are a serious threat associated with global epidemic clones and a variety of carbapenemase gene classes. In this study, we describe the molecular epidemiology, including whole-genome sequencing analysis and antimicrobial susceptibility profiles of 92 selected, nonredundant CRAB collected through public health efforts in the United States from 2013 to 2017. Among the 92 isolates, the Oxford (OX) multilocus sequence typing scheme identified 30 sequence types (STs); the majority of isolates (n = 59, 64%) represented STs belonging to the international clonal complex 92 (CC92(OX)). Among these, ST208(OX) (n = 21) and ST281(OX) (n = 20) were the most common. All isolates carried an OXA-type carbapenemase gene, comprising 20 alleles. Ninety isolates (98%) encoded an intrinsic OXA-51-like enzyme; 67 (73%) harbored an additional acquired bla(OXA) gene, most commonly bla(OXA-23) (n = 45; 49%). Compared with isolates harboring only intrinsic oxacillinase genes, acquired bla(OXA) gene presence was associated with higher prevalence of resistance and a higher median minimum inhibitory concentration to the carbapenem imipenem (64 μg/mL vs. 8 μg/mL), and antibiotics from other drug classes, including penicillin, aminoglycosides, cephalosporins, and polymyxins. These data illustrate the wide distribution of CC92(OX) and high prevalence of acquired bla(OXA) carbapenemase genes among CRAB in the United States. |
Development and Validation of a Clinical Laboratory Improvement Amendments-Compliant Multiplex Real-Time PCR Assay for Detection of mcr Genes.
Daniels JB , Campbell D , Boyd S , Ansari U , Lutgring J , Rasheed JK , Halpin AL , Sjolund-Karlsson M . Microb Drug Resist 2019 25 (7) 991-996 Increased use of colistin in both human and veterinary medicine has led to the emergence of plasmid-mediated colistin resistance (mcr genes). In this study, we report the development of a real-time PCR assay using TaqMan probe-based chemistry for detection of mcr genes from bacterial isolates. Positive control isolates harboring mcr-1 and mcr-2 yielded exponential amplification curves with the assay, and the amplification efficiency was 98% and 96% for mcr-1 and mcr-2, respectively. Each target gene could be reproducibly detected from a sample containing 10(3) cfu/mL of mcr-harboring bacteria, and there was no cross-reactivity with DNA extracted from several multidrug-resistant bacteria harboring other resistance genes, but lacking mcr genes. Both sensitivity and specificity of the mcr real-time PCR assay were 100% in a method validation performed with a set of 25 previously well-characterized bacterial isolates containing mcr-positive and -negative bacteria. This newly developed assay is a rapid and sensitive tool for detecting emerging mcr genes in cultured bacterial isolates. The assay was successfully validated according to quality standards of the Clinical Laboratory Improvement Amendments (CLIA). |
Genomic Analysis of a Pan-Resistant Isolate of Klebsiella pneumoniae , United States 2016.
de Man TJB , Lutgring JD , Lonsway DR , Anderson KF , Kiehlbauch JA , Chen L , Walters MS , Sjolund-Karlsson M , Rasheed JK , Kallen A , Halpin AL . mBio 2018 9 (2) Antimicrobial resistance is a threat to public health globally and leads to an estimated 23,000 deaths annually in the United States alone. Here, we report the genomic characterization of an unusual Klebsiella pneumoniae, nonsusceptible to all 26 antibiotics tested, that was isolated from a U.S. PATIENT: The isolate harbored four known beta-lactamase genes, including plasmid-mediated blaNDM-1 and blaCMY-6, as well as chromosomal blaCTX-M-15 and blaSHV-28, which accounted for resistance to all beta-lactams tested. In addition, sequence analysis identified mechanisms that could explain all other reported nonsusceptibility results, including nonsusceptibility to colistin, tigecycline, and chloramphenicol. Two plasmids, IncA/C2 and IncFIB, were closely related to mobile elements described previously and isolated from Gram-negative bacteria from China, Nepal, India, the United States, and Kenya, suggesting possible origins of the isolate and plasmids. This is one of the first K. pneumoniae isolates in the United States to have been reported to the Centers for Disease Control and Prevention (CDC) as nonsusceptible to all drugs tested, including all beta-lactams, colistin, and tigecycline.IMPORTANCE Antimicrobial resistance is a major public health threat worldwide. Bacteria that are nonsusceptible or resistant to all antimicrobials available are of major concern to patients and the public because of lack of treatment options and potential for spread. A Klebsiella pneumoniae strain that was nonsusceptible to all tested antibiotics was isolated from a U.S. PATIENT: Mechanisms that could explain all observed phenotypic antimicrobial resistance phenotypes, including resistance to colistin and beta-lactams, were identified through whole-genome sequencing. The large variety of resistance determinants identified demonstrates the usefulness of whole-genome sequencing for detecting these genes in an outbreak response. Sequencing of isolates with rare and unusual phenotypes can provide information on how these extremely resistant isolates develop, including whether resistance is acquired on mobile elements or accumulated through chromosomal mutations. Moreover, this provides further insight into not only detecting these highly resistant organisms but also preventing their spread. |
Development of a pefloxacin disk diffusion method for detection of fluoroquinolone-resistant Salmonella enterica
Skov R , Matuschek E , Sjolund-Karlsson M , Ahman J , Petersen A , Stegger M , Torpdahl M , Kahlmeter G . J Clin Microbiol 2015 53 (11) 3411-7 Fluoroquinolones are among the drugs of choice for treatment of salmonella infections. However, fluroquinolone resistance is increasing in salmonella due to chromosomal mutations in the quinolone resistance-determining region (QRDR) of the topoisomerase genes gyrA, gyrB, parC and parE and/or plasmid-mediated quinolone resistance (PMQR) mechanisms including qnr variants, aac(6' )-Ib-cr, qepA and oqxAB. Some of these cause only subtle increases of the MIC i.e, MICs ranging from 0.12 - 0.25 mg/L for ciprofloxacin (just above the wild type MIC of ≤0.06 mg/L). These isolates are difficult to detect with standard ciprofloxacin disk diffusion, and plasmid mediated resistance such as qnr are often not detected by the nalidixic acid screen test. We evaluated 16 quinolone/fluoroquinolone disks for their ability to detect low-level resistant Salmonella non-typhi isolates. A total of 153 Salmonella isolates characterized for the presence (N=104) or absence (N=49) of gyrA/parC topoisomerase mutations, qnrA, qnrB, qnrD, qnrS, aac(6' )-lb-cr or qepA genes were investigated. All isolates were MIC tested by broth micro-dilution against ciprofloxacin, levofloxacin and ofloxacin and by disk diffusion using EUCAST/CLSI methodology. MIC determination correctly categorized all isolates as either wildtype (MICs ≤0.06 mg/L and absence of resistance genes) or non-wildtype (MIC >0.06 mg/L and presence of a resistance gene). Disk diffusion using these antibiotics and nalidixic acid failed to detect some low-level resistant isolates whereas the pefloxacin 5 mug disk correctly identified all resistant isolates. However, pefloxacin will not detect isolates having aac(6' )-Ib-cr as the only resistance determinant. The pefloxacin disk assay was approved and implemented by EUCAST(2014) and CLSI(2015). |
Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive Salmonella infections
Crump JA , Sjolund-Karlsson M , Gordon MA , Parry CM . Clin Microbiol Rev 2015 28 (4) 901-37 Salmonella enterica infections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses and may be associated with a high case fatality ratio. Microbiologic culture of blood or bone marrow remains the mainstay of laboratory diagnosis. Antimicrobial resistance has emerged in Salmonella enterica, initially to the traditional first-line drugs chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. Decreased fluoroquinolone susceptibility and then fluoroquinolone resistance have developed in association with chromosomal mutations in the quinolone resistance-determining region of genes encoding DNA gyrase and topoisomerase IV and also by plasmid-mediated resistance mechanisms. Resistance to extended-spectrum cephalosporins has occurred more often in nontyphoidal than in typhoidal Salmonella strains. Azithromycin is effective for the management of uncomplicated typhoid fever and may serve as an alternative oral drug in areas where fluoroquinolone resistance is common. In 2013, CLSI lowered the ciprofloxacin susceptibility breakpoints to account for accumulating clinical, microbiologic, and pharmacokinetic-pharmacodynamic data suggesting that revision was needed for contemporary invasive Salmonella infections. Newly established CLSI guidelines for azithromycin and Salmonella enterica serovar Typhi were published in CLSI document M100 in 2015. |
Plasmid-mediated quinolone resistance in isolates of Salmonella enterica serotype Typhi, USA.
Sjolund-Karlsson M , Howie R , Rickert R , Newton A , Gonzalez-Aviles G , Crump JA . Int J Antimicrob Agents 2014 45 (1) 88-90 Salmonella enterica serotype Typhi is the causative agent of typhoid fever, a severe, systemic, febrile illness. The infection is usually acquired through consumption of water or food contaminated with human faecal material and is therefore more common in areas with poor sanitation and crowding. Typhoid fever was estimated to cause 11.9 million illnesses and 129 000 deaths in 2010 [1]. A large proportion of typhoid fever occurs among infants and children in South-Central and Southeast Asia. Typhoid fever in the USA is often associated with international travel. | Timely treatment with appropriate antimicrobial agents is critical for optimal management of typhoid fever. However, resistance to traditional first-line antimicrobial agents (chloramphenicol, ampicillin and trimethoprim/sulfamethoxazole) is common and has prompted the use of other drugs such as fluoroquinolones (e.g. ciprofloxacin) [2]. In the USA, antimicrobial susceptibility among S. Typhi is monitored by the National Antimicrobial Resistance Monitoring System (NARMS) at the US Centers for Disease Control and Prevention (CDC). |
Shigellosis with decreased susceptibility to azithromycin
Heiman KE , Grass JE , Sjolund-Karlsson M , Bowen A . Pediatr Infect Dis J 2014 33 (11) 1204-5 Shigella with decreased susceptibility to azithromycin (DSA-Shigella) is emerging in the United States.1 This is concerning because azithromycin is recommended for treatment of multidrug-resistant shigellosis among children and adults.2 In the United States, Shigella causes approximately 500,000 illnesses annually, mainly in children <10 years of age, and it can cause large school- and childcare-associated outbreaks.3 Because clinical guidelines for determining susceptibility of Shigella to azithromycin do not exist, DSA-Shigella isolates are difficult to identify and treatment decisions must be made without azithromycin susceptibility data. | We identified DSA-Shigella isolates through the National Antimicrobial Resistance Monitoring System (NARMS), which in 2011 began measuring azithromycin minimum inhibitory concentrations among all Shigella isolates submitted from public health laboratories to Centers for Disease Control and Prevention for routine surveillance and outbreak evaluation (∼5% of US Shigella isolates). Additional DSA-Shigella isolates were identified through NARMS retrospective studies.1 We defined DSA as azithromycin minimum inhibitory concentration >16 μg/mL using broth microdilution.1 Macrolide resistance genes mphA and ermB were detected using polymerase chain reaction. |
Performance of Etest and disk diffusion for the detection of ciprofloxacin and levofloxacin resistance in Salmonella
Deak E , Hindler JA , Skov R , Sjolund-Karlsson M , Sokovic A , Humphries RM . J Clin Microbiol 2014 53 (1) 298-301 Etest and disk diffusion were compared to broth microdilution for the detection of fluoroquinolone resistance in 135 typhoidal and non-typhoidal serovars of Salmonella. Categorical agreement for ciprofloxacin and levofloxacin Etest was 89.6 and 83.7%, respectively. Disk diffusion categorical agreement was 88.2 and 93.3%, respectively. The only errors observed were minor errors. |
Fluoroquinolone susceptibility testing of Salmonella enterica: detection of acquired resistance and selection of zone diameter breakpoints for levofloxacin and ofloxacin
Sjolund-Karlsson M , Howie RL , Crump JA , Whichard JM . J Clin Microbiol 2014 52 (3) 877-84 Fluoroquinolones (e.g., ciprofloxacin) have become a mainstay for treating severe Salmonella infections in adults. Fluoroquinolone resistance in Salmonella is mostly due to mutations in the topoisomerase genes, but plasmid-mediated quinolone resistance (PMQR) mechanisms have also been described. In 2012, the Clinical and Laboratory Standards Institute (CLSI) revised the ciprofloxacin interpretive criteria (breakpoints) for disk diffusion and MIC test methods for Salmonella. In 2013, the CLSI published MIC breakpoints for Salmonella to levofloxacin and ofloxacin, but breakpoints for assigning disk diffusion results to susceptible (S), intermediate (I), and resistant (R) categories are still needed. In this study, the MICs and inhibition zone diameters for nalidixic acid, ciprofloxacin, levofloxacin, and ofloxacin were determined for 100 clinical isolates of nontyphi Salmonella with or without resistance mechanisms. We confirmed that the new levofloxacin MIC breakpoints resulted in the highest category agreement (94%) when plotted against the ciprofloxacin MICs and that the new ofloxacin MIC breakpoints resulted in 92% category agreement between ofloxacin and ciprofloxacin. By applying the new MIC breakpoints in the MIC zone scattergrams for levofloxacin and ofloxacin, the following disk diffusion breakpoints generated the least number of errors: ≥28 mm (S), 19 to 27 mm (I), and ≤18 mm (R) for levofloxacin and ≥25 mm (S), 16 to 24 mm (I), and ≤15 mm (R) for ofloxacin. Neither the levofloxacin nor the ofloxacin disk yielded good separation of isolates with and without resistance mechanisms. Further studies will be needed to develop a disk diffusion assay that efficiently detects all isolates with acquired resistance to fluoroquinolones. |
Occurrence of ß-lactamase genes among non-Typhi Salmonella enterica isolated from humans, food animals, and retail meats in the United States and Canada.
Sjolund-Karlsson M , Howie RL , Blickenstaff K , Boerlin P , Ball T , Chalmers G , Duval B , Haro J , Rickert R , Zhao S , Fedorka-Cray PJ , Whichard JM . Microb Drug Resist 2013 19 (3) 191-7 Non-Typhi Salmonella cause over 1.7 million cases of gastroenteritis in North America each year, and food-animal products are commonly implicated in human infections. For invasive infections, antimicrobial therapy is indicated. In North America, the antimicrobial susceptibility of Salmonella is monitored by the U.S. National Antimicrobial Resistance Monitoring System (NARMS) and The Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). In this study, we determined the susceptibility to cephalosporins by broth microdilution among 5,041 non-Typhi Salmonella enterica isolated from food animals, retail meats, and humans. In the United States, 109 (4.6%) of isolates collected from humans, 77 (15.7%) from retail meat, and 140 (10.6%) from food animals displayed decreased susceptibility to cephalosporins (DSC). Among the Canadian retail meat and food animal isolates, 52 (13.0%) and 42 (9.4%) displayed DSC. All isolates displaying DSC were screened for beta-lactamase genes (bla(TEM), bla(SHV), bla(CMY), bla(CTX-M), and bla(OXA-1)) by polymerase chain reaction. At least one beta-lactamase gene was detected in 74/109 (67.9%) isolates collected from humans, and the bla(CMY) genes were most prevalent (69/109; 63.3%). Similarly, the bla(CMY) genes predominated among the beta-lactamase-producing isolates collected from retail meats and food animals. Three isolates from humans harbored a bla(CTX-M-15) gene. No animal or retail meat isolates harbored a bla(CTX-M) or bla(OXA-1) gene. A bla(TEM) gene was found in 5 human, 9 retail meat, and 17 animal isolates. Although serotype distributions varied among human, retail meat, and animal sources, overlap in bla(CMY)-positive serotypes across sample sources supports meat and food-animal sources as reservoirs for human infection. |
Outbreak of infections caused by Shigella sonnei with reduced susceptibility to azithromycin, United States
Sjolund Karlsson M , Bowen A , Reporter R , Folster JP , Grass JE , Howie RL , Taylor J , Whichard JM . Antimicrob Agents Chemother 2012 57 (3) 1559-60 Shigellosis is the third most common enteric bacterial infection in the United States (9).... |
Drug-resistance mechanisms in Vibrio cholerae O1 outbreak strain, Haiti, 2010.
Sjolund-Karlsson M , Reimer A , Folster JP , Walker M , Dahourou GA , Batra DG , Martin I , Joyce K , Parsons MB , Boncy J , Whichard JM , Gilmour MW . Emerg Infect Dis 2011 17 (11) 2151-2154 To increase understanding of drug-resistant Vibrio cholerae, we studied selected molecular mechanisms of antimicrobial drug resistance in the 2010 Haiti V. cholerae outbreak strain. Most resistance resulted from acquired genes located on an integrating conjugative element showing high homology to an integrating conjugative element identified in a V. cholerae isolate from India. |
Antimicrobial susceptibility to azithromycin among Salmonella enterica isolated in the United States
Sjolund-Karlsson M , Joyce K , Blickenstaff K , Ball T , Haro J , Medalla FM , Fedorka-Cray P , Zhao S , Crump JA , Whichard JM . Antimicrob Agents Chemother 2011 55 (9) 3985-9 Due to emerging resistance to traditional antimicrobial agents such as ampicillin, trimethoprim-sulfamethoxazole and chloramphenicol, azithromycin is increasingly used for the treatment of invasive Salmonella infections. In the present study, 696 isolates of non-Typhi Salmonella collected from humans, food animals and retail meats in the United States were investigated for antimicrobial susceptibility to azithromycin. Seventy two Salmonella enterica serotype Typhi isolated from humans were also tested. For each isolate, minimum inhibitory concentrations (MICs) to azithromycin and 15 other antimicrobial agents were determined by broth microdilution. Among the non-Typhi Salmonella isolates, azithromycin MICs among human isolates ranged from 1-32 mcg/mL whereas the MICs among the animal and retail meat isolates ranged from 2-16 mcg/mL and 4-16 mcg/mL, respectively. Among Salmonella ser. Typhi isolates the azithromycin MICs ranged from 4-16 mcg/mL. The highest MIC observed in the present study was 32 mug/mL and was detected in three isolates from humans belonging to serotypes Kentucky, Montevideo and Paratyphi A. Based on our findings, we propose an epidemiological cut-off value (ECOFF) of wild type ≤ 16 mcg/mL for azithromycin and Salmonella. The susceptibility data provided could be used in combination with clinical outcome data to determine tentative clinical breakpoints for azithromycin and Salmonella enterica. |
Ciprofloxacin-resistant Salmonella enterica serotype Typhi, United States, 1999-2008
Medalla F , Sjolund-Karlsson M , Shin SH , Harvey E , Joyce K , Theobald L , Nygren BL , Pecic G , Gay K , Austin J , Stuart A , Blanton E , Mintz ED , Whichard JM , Barzilay EJ . Emerg Infect Dis 2011 17 (6) 1095-1098 We report 9 ciprofloxacin-resistant Salmonella enterica serotype Typhi isolates submitted to the US National Antimicrobial Resistance Monitoring System during 1999-2008. The first 2 had indistinguishable pulsed-field gel electrophoresis patterns and identical gyrA and parC mutations. Eight of the 9 patients had traveled to India within 30 days before illness onset. |
CTX-M-producing non-Typhi Salmonella spp. isolated from humans, United States
Sjolund-Karlsson M , Howie R , Krueger A , Rickert R , Pecic G , Lupoli K , Folster JP , Whichard JM . Emerg Infect Dis 2011 17 (1) 97-9 CTX-M-type Beta-lactamases are increasing among US Enterobacteriaceae isolates. Of 2,165 non-Typhi Salmonella isolates submitted in 2007 to the National Antimicrobial Resistance Monitoring System, 100 (4.6%) displayed elevated MICs (≥2 mg/L) of ceftriaxone or ceftiofur. Three isolates (serotypes Typhimurium, Concord, and I 4,5,12:i:-) contained blaCTX-M-5, blaCTX-M-15, and blaCTX-M-55/57, respectively. |
Salmonella isolates with decreased susceptibility to extended-spectrum cephalosporins in the United States
Sjolund-Karlsson M , Rickert R , Matar C , Pecic G , Howie RL , Joyce K , Medalla F , Barzilay EJ , Whichard JM . Foodborne Pathog Dis 2010 7 (12) 1503-9 OBJECTIVE: We describe the antimicrobial susceptibility to extended-spectrum cephalosporins in non-Typhi Salmonella (NTS) isolated from humans in the United States and explore resistance mechanisms for isolates displaying decreased susceptibility to ceftriaxone or ceftiofur. We further explore the concordance between the newly revised Clinical and Laboratory Standards Institute (CLSI) breakpoints for ceftriaxone and the presence of a beta-lactamase. METHODS: In 2005 and 2006, public health laboratories in all U.S. state health departments forwarded every 20th NTS isolate from humans to Centers for Disease Control and Prevention as part of the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. Isolates displaying decreased susceptibility (MIC ≥ 2 mg/L) to ceftriaxone or ceftiofur were included in the study. The presence of beta-lactamase genes was investigated by polymerase chain reaction amplification and sequencing, targeting six different genes (bla(TEM), bla(OXA), bla(SHV), bla(CTX-M), bla(PSE), and bla(CMY)). Plasmid location of bla(CMY) was confirmed by transforming plasmids into Escherichia coli. RESULTS: Among the 4236 isolates of NTS submitted to NARMS in 2005 and 2006, 175 (4.1%) displayed decreased susceptibility to either ceftriaxone or ceftiofur. By polymerase chain reaction screening, one or more beta-lactamase genes could be detected in 139 (80.8%) isolates. The most prevalent resistance mechanism detected was the AmpC beta-lactamase gene bla(CMY.) Other beta-lactamase genes detected included 11 bla(TEM-1), 3 bla(PSE-1), 2 bla(OXA-1), and 1 bla(CTX-M-15). The ceftriaxone MIC values for the bla(CMY)-containing isolates ranged from 4 to 64 mg/L; all bla(CMY)-bearing isolates were classified as ceftriaxone resistant according to current CLSI guidelines. CONCLUSIONS: Among NTS isolates submitted to NARMS in 2005 and 2006, cephamycinase beta-lactamases are the predominant cause of decreased susceptibility to ceftriaxone. The fact that all bla(CMY)-containing isolates were classified as resistant to ceftriaxone (MIC ≥ 4 mg/L) supports the newly revised CLSI breakpoints for cephalosporins and Enterobacteriaceae. |
Plasmid-mediated quinolone resistance among non-Typhi Salmonella enterica isolates, USA
Sjolund-Karlsson M , Howie R , Rickert R , Krueger A , Tran TT , Zhao S , Ball T , Haro J , Pecic G , Joyce K , Fedorka-Cray PJ , Whichard JM , McDermott PF . Emerg Infect Dis 2010 16 (11) 1789-91 We determined the prevalence of plasmid-mediated quinolone resistance mechanisms among non-Typhi Salmonella spp. isolated from humans, food animals, and retail meat in the United States in 2007. Six isolates collected from humans harbored aac(6')Ib-cr or a qnr gene. Most prevalent was qnrS1. No animal or retail meat isolates harbored a plasmid-mediated mechanism. |
Little evidence for reversibility of trimethoprim resistance after a drastic reduction in trimethoprim use
Sundqvist M , Geli P , Andersson DI , Sjolund-Karlsson M , Runehagen A , Cars H , Abelson-Storby K , Cars O , Kahlmeter G . J Antimicrob Chemother 2010 65 (2) 350-60 OBJECTIVES: The worldwide rapid increase in antibiotic-resistant bacteria has made efforts to prolong the lifespan of existing antibiotics very important. Antibiotic resistance often confers a fitness cost in the bacterium. Resistance may thus be reversible if antibiotic use is discontinued or reduced. To examine this concept, we performed a 24 month voluntary restriction on the use of trimethoprim-containing drugs in Kronoberg County, Sweden. METHODS: The intervention was performed on a 14 year baseline of monthly data on trimethoprim resistance and consumption. A three-parameter mathematical model was used to analyse the intervention effect. The prerequisites for reversion of resistance (i.e. fitness cost, associated resistance and clonal composition) were studied on subsets of consecutively collected Escherichia coli from urinary tract infections. RESULTS: The use of trimethoprim-containing drugs decreased by 85% during the intervention. A marginal but statistically significant effect on the increase in trimethoprim resistance was registered. There was no change in the clonal composition of E. coli and there was no measurable fitness cost associated with trimethoprim resistance in clinical isolates. The frequency of associated antibiotic resistances in trimethoprim-resistant isolates was high. CONCLUSIONS: A lack of detectable fitness cost of trimethoprim resistance in vitro together with a strong co-selection of other antibiotics could explain the rather disappointing effect of the intervention. The result emphasizes the low possibility of reverting antibiotic resistance once established and the urgent need for the development of new antibacterial agents. |
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