Emergence Of Fluoroquinolone Resistance Research Articles

Global impact of antibacterial resistance in patients with hematologic malignancies and hematopoietic cell transplant recipients.

Patients with hematologic malignancies and hematopoietic cell transplant (HCT) recipients are at high risk of developing bacterial infections. These patients may suffer severe consequences from these infections if they do not receive immediate effective therapies, and thus are uniquely threatened by antimicrobial-resistant bacteria. Here, we outline how the emergence of specific resistant bacteria threatens the effectiveness of established approaches to prevent and treat infections in this population. The emergence of fluoroquinolone resistance among Enterobacterales and viridans group streptococci may decrease the effectiveness of fluoroquinolone prophylaxis during neutropenia. The emergence of Enterobacterales that produce extended-spectrum β-lactamases or carbapenemases and of increasingly resistant Pseudomonas aeruginosa may result in neutropenic patients experiencing delayed time to active antibacterial therapy, and consequently worse clinical outcomes. The ability to select targeted antibacterial therapies after the availability of susceptibility data may be limited in patients infected with metallo-β-lactamase-producing Enterobacterales and difficult-to-treat P. aeruginosa. Vancomycin-resistant enterococci and Stenotrophomonas maltophilia can cause breakthrough infections in patients already being treated with broad-spectrum β-lactam antibiotics. Resistance can also limit the ability to provide oral stepdown antibacterial therapy for patients who could otherwise be discharged from hospitalization. We also outline strategies that have the potential to mitigate the negative impact of antimicrobial resistance, including interventions based on active screening for colonization with resistant bacteria and the use of novel rapid diagnostic assays. Additional research is needed to better understand how these strategies can be leveraged to combat the emerging crisis of antimicrobial resistance in patients with hematologic malignancies and HCT recipients.

Concerning Trend in Ceftriaxone Minimum Inhibitory Concentration (MIC): Implications for the Treatment of Enteric Fever

Introduction:Salmonella typhi and paratyphi - related enteric fever still poses serious health risks to people all over the world. Ceftriaxone and azithromycin were recommended as the preferred treatments for enteric fever following the emergence of fluoroquinolone resistance. Several reports of ceftriaxone resistance have also been reported, hence accurate medication susceptibility tracking is essential to maintain the empiric management of enteric fever. This study’s objective is to determine the MIC of ceftriaxone in order to help clinicians prescribe the right dosage and stop the emergence of resistance. Material and Methods: The investigation was carried out in 800 bedded hospital in Ghaziabad using a cross-sectional prospective design. A total of 228 Salmonella isolates were included in this investigation. The isolates’ antibiotic susceptibility was assessed using the Kirby Bauer disc diffusion method, and the ceftriaxone MIC was calculated using the Broth Micro-Dilution (BMD) method. Result: Of the 228 Salmonella species that were isolated, 64 (28.07%) were Salmonella paratyphi A, and 164 (71.92%) were Salmonellatyphi. Ceftriaxone resistance was found in 33 (20.12%) Salmonellatyphi strains while it was found in 14 (21.87%) S. paratyphi A strains. 0.125 μg/ml was the ceftriaxone MIC50 value for S. typhi as well as for paratyphi A but the MIC90 value was 8 μg/ml in S. typhi and 4 μg/ml in S. paratyphi A isolates. Conclusion: This investigation revealed a concerning rise in the MIC to ceftriaxone and the reemergence of sensitivity to first-line medications.

Phylogenomic investigation of an outbreak of fluoroquinolone-resistant Salmonella enterica subsp. enterica serovar Paratyphi A in Phnom Penh, Cambodia.

In early 2020, the Medical Biology Laboratory of the Pasteur Institute of Cambodia isolated an unusually high number of fluoroquinolone-resistant Salmonella enterica subspecies enterica serovar Paratyphi A strains during its routine bacteriological surveillance activities in Phnom Penh, Cambodia. A public-health investigation was supported by genome sequencing of these Paratyphi A strains to gain insights into the genetic diversity and population structure of a potential outbreak of fluoroquinolone-resistant paratyphoid fever. Comparative genomic and phylodynamic analyses revealed the 2020 strains were descended from a previously described 2013-2015 outbreak of Paratyphi A infections. Our analysis showed sub-lineage 2.3.1 had remained largely susceptible to fluoroquinolone drugs until 2015, but acquired chromosomal resistance to these drugs during six separate events between late 2012 and 2015. The emergence of fluoroquinolone resistance was rapidly followed by the replacement of the original susceptible Paratyphi A population, which led to a dramatic increase of fluoroquinolone-resistant blood-culture-confirmed cases in subsequent years (2016-2020). The rapid acquisition of resistance-conferring mutations in the Paratyphi A population over a 3 year period is suggestive of a strong selective pressure on that population, likely linked with fluoroquinolone use. In turn, emergence of fluoroquinolone resistance has led to increased use of extended-spectrum cephalosporins like ceftriaxone that are becoming the drug of choice for empirical treatment of paratyphoid fever in Cambodia.

Emergence of Fluoroquinolone resistance and carbapenemase plasmids in Enterobacter cloacae isolated from Egyptian Pediatric Hospital

Emergence of Fluoroquinolone resistance and carbapenemase plasmids in Enterobacter cloacae isolated from Egyptian Pediatric Hospital

Emergence of fluoroquinolone resistance and possible mechanisms in clinical isolates of Stenotrophomonas maltophilia from Iran

Stenotrophomonas maltophilia exhibits wide spectrum of fluoroquinolone resistance using different mechanisms as multidrug efflux pumps and Smqnr alleles. Here, the role of smeDEF, smeVWX efflux genes and contribution of Smqnr alleles in the development of fluoroquinolone resistance was assessed. Ciprofloxacin, levofloxacin and moxifloxacin resistance were found in 10.9%, 3.5%, and 1.6% of isolates, respectively. More than four-fold differences in ciprofloxacin MICs were detected in the presence of reserpine and smeD, F, V expression was significantly associated with ciprofloxacin resistance (p = 0.017 for smeD, 0.003 for smeF, and 0.001 for smeV). Smqnr gene was found in 52% of the ciprofloxacin-resistant isolates and Smqnr8 was the most common allele detected. Fluoroquinolone resistance in S. maltophilia clinical isolates was significantly associated with active efflux pumps. There was no correlation between the Smqnr alleles and ciprofloxacin resistance; however, contribution of the Smqnr genes in low-level levofloxacin resistance was revealed.

The Relation Between the Emergence of Fluoroquinolone Resistance and Fluoroquinolone Exposure in New Cases of Active Pulmonary Tuberculosis.

This study aimed to determine the ratio of fluoroquinolone (FQ) exposure before the diagnosis of patients with a new case of active pulmonary tuberculosis (TB) and to investigate the correlation of this treatment with the emergence of FQ-resistant strains. In this retrospective comparative case series study, a total of 132 patients, who had been diagnosed with adult, culture-positive, active pulmonary TB were reviewed. The FQ group had 30 patients who had had ≥1 time and ≥7 days of FQ exposure within 1 year before the diagnoses. The control group included an equal number of patients with TB with similar demographic characteristics (non-FQ group). Ofloxacin (OFX) and moxifloxacin (MFX) resistance were examined at 2 different concentrations (2 and 4 mg/L for OFX; 0.25 and 0.5 mg/L for MFX). Of the 132 patients, 30 (22%) had 7 days or longer of FQ monotherapy within 1 year of initiation of anti-TB treatment. FQ resistance was detected in 2 (3.3%) patients. In the FQ group, MFX resistance at 0.25 mg/L concentration was observed in 1 patient, whereas another patient had OFX and MFX resistance at 4 mg/L and 0.5 mg/L concentrations, respectively. In the non-FQ group, no FQ resistance was detected in any of the patients. No statistically significant difference in terms of development of FQ resistance was found between the ratios of FQ and non-FQ groups (p=0.492). Although there was no statistically significant difference, 2 patients, in whom resistance was detected, had FQ exposure before their diagnosis. The FQ exposure ratio before the diagnosis is high (22%) in this cohort that includes patients with new active pulmonary TB, and the presence of patients with FQ resistance (even if only a few) should be a noteworthy and cautionary result in terms of FQ exposure and resistance development.

Epidemiology and Antimicrobial Susceptibility of Salmonella enterica Bloodstream Isolates Among Febrile Children in a Rural District in Northeastern Tanzania: A Cross-sectional Study.

Background Salmonella enterica including Salmonella Typhi and nontyphoidal Salmonella (NTS) are the predominant cause of community-acquired bloodstream infections in sub-Saharan Africa (sSA). Multiple-drug resistance and emerging fluoroquinolone resistance are of concern. Data on the age distribution of typhoid fever in sSA are scarce but essential for typhoid conjugate vaccine policy. We sought to describe Salmonella bloodstream infections, antimicrobial resistance, and age distribution at a rural district hospital in northeastern Tanzania.MethodsFrom 2008 to 2016, febrile children or children with a history of fever aged 1 month to 5 years admitted to Korogwe District Hospital were enrolled. Demographic, clinical data and blood cultures were collected. Organisms were identified by conventional microbiological methods, and antimicrobial susceptibility test was done by disc diffusion.ResultsOf 4176 participants receiving blood cultures, 383 (9.2 %) yielded pathogens. Of pathogens, 171 (44.6%) were Salmonella enterica of which 129 (75.4%) were Salmonella Typhi, and 42 (24.6%) were NTS. The median (interquartile range age of participants was 13.1 (6.3–28.0) months for those with Salmonella Typhi and 11.5 (8.5–23.4) months for NTS. Of 129 Salmonella Typhi, 89 (89.9%) were resistant to amoxicillin, 85 (81.0%) to chloramphenicol, and 93 (92.1%) to trimethoprim-sulfamethoxazole compared with 22 (62.9%), 15 (39.4%), and 27 (79.4%), respectively, for NTS. Multidrug resistance was present in 68 (81.0%) of Salmonella Typhi and 12 (41.4%) of NTS.Conclusion Salmonella Typhi was the leading cause of bloodstream infection among infants and young children <2 years of age admitted to Korogwe District Hospital. Multidrug resistance was common, highlighting a role for typhoid conjugate vaccine into routine infant vaccine schedules.

Reconsidering azithromycin disc diffusion interpretive criteria for Salmonellae in view of azithromycin MIC creep among typhoidal and nontyphoidal salmonella.

PURPOSE:Enteric fever continues to be an important public health challenge for the developing world. With the emergence of fluoroquinolone resistance in Salmonellae spp. azithromycin is increasingly being used for oral treatment of enteric fever. We investigated the antibiotic susceptibility pattern of azithromycin in Salmonellae spp. isolates from a tertiary care hospital to detect emerging resistance.METHODS:The study assessed the reliability of disc diffusion as a screening test to detect azithromycin resistance by comparing it with the minimum inhibitory concentrations (MICs) of the drug in 100 Salmonellae spp. strains. The strains of Salmonellae spp. showing resistance to azithromycin were further investigated for resistance markers – mphA, mphB, and mef B genes.RESULTS:This study was conducted on 100 Salmonella enterica strains recovered from blood culture samples between 2013 and 2017. Among these isolates, 18 showed resistance to azithromycin by disc diffusion methodology with zones of inhibition <13 mm. MIC of 6 of these isolates were ≥32 mg/L. The mean MIC of azithromycin increased from 5 mg/L in 2013 to 24 mg/L in 2017. Azithromycin consumption as defined daily doses per 1000 patient days also showed an increase over the past 4 years.CONCLUSION:Azithromycin disc diffusion diameter interpretations as recommended by Clinical and Laboratory Standards Institute can mislabel a few sensitive strains as resistant. Azithromycin resistance is emerging in typhoidal and nontyphoidal Salmonella. MphA gene is associated with high MICs in nontyphoidal Salmonella spp.

Impact of fluoroquinolone prophylaxis during neutropenia on bloodstream infection: Data from a surveillance program in 8755 patients receiving high-dose chemotherapy for haematologic malignancies between 2009 and 2014

Antibacterial chemoprophylaxis with fluoroquinolones (FQPx) has been commonly used in cancer patients with neutropenia, but its efficacy has been challenged by the emergence of fluoroquinolone resistance. The impact of FQPx on bloodstream infections (BSI) during neutropenia after high-dose chemotherapy for haematologic malignancies was evaluated through a multicenter hospital infection surveillance system for the period 2009-2014. Among 8755 patients (4223 allogeneic [allo-] HSCT, 3602 autologous [auto-] HSCT, 930 high-dose chemotherapy for acute leukemia [HDC]), 5302 (61%) had received FQPx. Administration of FQPx was associated with fewer Gram-negative BSI in the overall study cohort patients (4.6% vs. 7.7%, adjusted subdistribution hazard ratio [aSHR] 0.59, 95%CI 0.50-0.70), in patients with HDC (3.7% vs. 9.2%, adjusted subdistribution hazard ratio [aSHR] 0.40, 95%CI 0.22-0.70) and auto-HSCT patients (4% vs. 9%, aSHR 0.43, 95%CI 0.33-0.56). In HDC patients, FQPx was associated with a marked reduction in all-cause mortality during neutropenia (2.3% vs. 7.8%, aSHR 0.30, 95%CI 0.15-0.58). Patients receiving FQPx had significantly more BSIs due to ESBL-positive Enterobacteriacea (0.8 vs. 0.3%, RR 2.2, 95%CI 1.17-4.26). BSIs by MRSA (n = 5) and VRE (n = 11) were rare in our cohort. As used in the participating centers, FQPx was associated with reduced Gram-negative BSI and improved survival among HDC patients. Among HSCT patients, the benefits were less clear. If adapted to local resistance patterns and patient characteristics, FQPx still may be useful in the management of patients with haematologic malignancies.

Out of Asia: the independent rise and global spread of fluoroquinolone-resistant Shigella.

Shigella are ranked among the most prevalent aetiologies of diarrhoeal disease worldwide, disproportionately affecting young children in developing countries and high-risk communities in developed settings. Antimicrobial treatment, most commonly with fluoroquinolones, is currently recommended for Shigella infections to alleviate symptoms and control disease transmission. Resistance to fluoroquinolones has emerged in differing Shigella species (S. dysenteriae, flexneri and sonnei) since the turn of the 21st century, originating in endemic areas, and latterly spreading into non-endemic regions. Despite occurring independently, the emergence of fluoroquinolone resistance in these different Shigella species shares striking similarities regarding their epidemiology and resistance mechanisms. Here, we review and discuss the current epidemiology of fluoroquinolone-resistant Shigella species, particularly in the light of recent genomic insights.

Emergence of Fluoroquinolone Resistance in Pigs, Nigeria

Emergence of Fluoroquinolone Resistance in Pigs, Nigeria

Species differences in ciprofloxacin resistance among Gram-negative bacteria: can “anti-mutant” ratios of the area under the concentration–time curve to the MIC be achieved clinically?

To explore if the ‘anti-mutant’ ratios of 24-h area under the concentration–time curve (AUC24) to the MIC overlap the clinically attainable AUC24/MICs, the selection of ciprofloxacin-resistant Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae mutants was studied in dynamic model that simulates human pharmacokinetics of ciprofloxacin. Four strains each of E. coli and P. aeruginosa and three strains of K. pneumoniae were exposed to ciprofloxacin over a 50–400-fold range of the AUC24/MIC ratio. Based on population analysis data, areas under the bacterial mutant concentration–time curves (AUBCMs) were determined for subpopulations resistant to 4×, 8× and 16× MIC of the antibiotic. The emergence of resistance among three Gram-negative organisms was concentration dependent. Based on the AUBCM vs. AUC24/MIC curves, the predicted ‘anti-mutant’ AUC24/MIC ratios were clinically attainable with E. coli but not with P. aeruginosa and K. pneumoniae. The emergence of fluoroquinolone resistance in a clinical setting can be predicted using dynamic models.

PCR-RFLP-Based Detection of Mutations in the Chromosomal Fluoroquinolone Targets g yr A and p ar C Genes of Acinetobacter b aumanii Clinical Isolates from a Tertiary Hospital in Cairo, Egypt

Background and Aim: Acinetobacter baumannii is one of the most antimicrobial resistant nosocomial pathogens encountered clinically worldwide. The emergence of fluoroquinolone resistance among A. baumannii isolates is currently of concern. This study aimed to investigate the antimicrobial susceptibility patterns among 49 clinical isolates of A baumannii collected from a tertiary care hospital in Egypt. These isolates were analysed for the mechanism of fluoroquinolone resistance based on the presence of mutations in the quinolone resistance-determining regions (QRDRs) of the chromosomal quinolone resistance determinants gyrA and parC genes. Methods: A. baumannii isolates were identified using conventional biochemical testing, VITEK 2 automated system and polymerase chain reaction (PCR) assay targeting the intrinsic blaOXA-51-like gene of A. baumannii species. Antimicrobial susceptibility to different antimicrobial agents was tested using agar disk diffusion method and the minimum inhibitory concentration (MIC) of ciprofloxacin was determined using E-test (bioMerieux, France) on Mueller-Hinton agar medium following the Clinical and Laboratory Standards Institute guidelines. The QRDRs of the gyrA and parC genes in A. baumannii isolates were amplified by PCR using specific primers. Mutations in theses QRDRs were detected by HinfI restriction fragment length polymorphism (RFLP) of PCR products and sequencing. Results: The blaOXA-51-like gene was detected in all isolates confirming identification as A. baumannii. Antimicrobial susceptibility study showed that all isolates (100 %) were MDR. They were 100 % resistant to the tested fluoroquinolones, ciprofloxacin and levofloxacin. The MIC of ciprofloxacin ranged from 4 to ≥ 32 μg/mL. All A. baumannii isolates (100 %) were found to harbour gyrA and parC genes. HinfI restriction analysis showed a detectable mutation in QRDRs at position Ser-83 of gyrA gene and Ser-80 of parC gene. There was single mutation in either gyrA or parC in 11 isolates showed ciprofloxacin MIC of < 32 μg/mL, while 38 isolates with MIC of ≥ 32 μg/mL had double mutations in QRDRs of both genes. Conclusions: Resistance of A. baumannii isolates to fluoroquinolones in Egypt is alarming as all MDR A. baumannii isolates in the current study were mostly highly resistant to ciprofloxacin with MIC ≥ 32 μg/mL, limiting the remaining therapeutic options and a public health policy on appropriate prescribing and thus the rational use of antimicrobial agents is required. Double mutation with substitutions at positions Ser-83 and Ser-80 of gyrA and parC genes, respectively, could lead to high‐level ciprofloxacin resistant phenotype than a single mutation in one of them. Further extensive studies including a larger number of isolates from different geographic areas in Egypt and investigating other fluoroquinolone resistance mechanisms are warranted.

Novel mutations in quinolone resistance-determining regions of gyrA, gyrB, parC and parE in Shigella flexneri clinical isolates from eastern Chinese populations between 2001 and 2011.

The aim of this study was to evaluate the prevalence of fluoroquinolone resistance and mechanisms of selected fluoroquinolone resistance in Shigella flexneri isolates. A total of 624 S. flexneri strains isolated between 2001 and 2011 in Jiangsu Province of China were analysed for their fluoroquinolone susceptibility. The quinolone resistance-determining region of gyrA, gyrB, parC and parE were amplified and sequenced. In general, 90.5% of S. flexneri exhibited resistance to nalidixic acid. The mean norfloxacin resistance rate was 22.4% during the 11years from 2001 to 2011 (6.4% from 2001 to 2005 and 36.8% from 2006 to 2011). Sequencing of gyrA, gyrB, parC and parE genes of all S. flexneri isolates showed that the mutation rate was as high as 93.9%. In addition, 91.8% and 92.3% of S. flexneri harboured mutations in gyrA and parC, respectively. About 35.2% of S. flexneri isolates susceptible to nalidixic acid contained mutations. Meanwhile, mutations were detected in 91.2% of norfloxacin-susceptible strains, and almost all S. flexneri isolates resistant to fluoroquinolone contained mutations. To the best of our knowledge, this is the first study reporting the occurrence of point mutations Asn57Lys and His80Pro in gyrA and Ala85Thr, Asp111His and Ser129Pro in parC. Emerging fluoroquinolone resistance with a significantly high mutation rate of the gyrA and parC genes in S. flexneri in Jiangsu Province deserves attention, and monitoring antibiotic susceptibility is important for the effective management of S. flexneri infections.

Trends of fluoroquinolone-resistant Escherichia coli amongst urinary isolates in children: a 10 year surveillance study.

We evaluated 3122 children with E. coli urinary isolates over a 10 year period in order to assess the emergence of fluoroquinolone resistance. Susceptibilities remained stable; however, hospitalized children had a statistically higher risk of developing fluoroquinolone-resistant isolates when compared with outpatients. Stewardship monitoring of fluoroquinolone use amongst hospitalized children is warranted.

Antibiotic prophylaxis for transrectal prostate biopsy-a new strategy.

Fluoroquinolones are extensively used as prophylaxis for transrectal ultrasound-guided biopsy of the prostate (TRUBP). Emerging fluoroquinolone resistance and selection of multiresistant organisms warrant new prophylactic strategies. Pivmecillinam and amoxicillin/clavulanic acid have mutual synergistic activity and the combination of these agents has a broad coverage of the majority of microorganisms causing infectious complications after TRUBP and may be a valuable future prophylactic regimen. This was a retrospective cohort study of 2624 men that underwent TRUBP at a Danish university hospital. The patients were divided into three groups. Group 1 (n = 1220) received ciprofloxacin before TRUBP, Group 2 (n = 240) received a combination of pivmecillinam and amoxicillin/clavulanic acid before TRUBP and Group 3 (n = 1161) received an extended prophylaxis with pivmecillinam and amoxicillin/clavulanic acid before and for 2 days after TRUBP. One hundred and ten out of 148 (74.3%) post-TRUBP infections were caused by Escherichia coli, Klebsiella pneumoniae or Enterococcus faecalis. Group 3 with the extended prophylaxis with pivmecillinam and amoxicillin/clavulanic acid had a significantly lower rate of bacteraemia (0.9%) as compared with Group 1 (1.8%) and Group 2 (3.7%). A significant fall in the proportion of ESBL-producing Enterobacteriaceae was observed from the period when ciprofloxacin was used as prophylaxis (8.1%) compared with the subsequent period when pivmecillinam and amoxicillin/clavulanic acid was used (5.9%). The combination of pivmecillinam and amoxicillin/clavulanic acid is an attractive prophylaxis for TRUBP from a clinical, bacteriological and ecological point of view as compared with ciprofloxacin.

The quest for the best metric of antibiotic use and its correlation with the emergence of fluoroquinolone resistance in children.

We evaluated the correlation between fluoroquinolone use, measured by doses administered and days of therapy, with the emergence of ciprofloxacin and levofloxacin resistance among Gram-negative bacilli infections in children hospitalized at one pediatric center between April 2001 and March 2009. Both metrics and drug resistance were highly correlated.

Decline ofSalmonella entericaSerotype Choleraesuis Infections, Taiwan

To the Editor: Human salmonellosis is a major public health problem of global concern. Salmonella enterica serotype Choleraesuis is a nontyphoid serotype; it has a narrow host range and is associated with a high proportion of invasive infections (50%–90% of isolates are from sterile sites [(1)]). In 2000, emergence of fluoroquinolone resistance in S. enterica Choleraesuis was reported from Chang Gung Memorial Hospital at Linkou, Taiwan (2). Since then, we have continuously monitored the trend of these infections at this hospital in northern Taiwan and at Chang Gung Memorial Hospital at Kaohsiung in southern Taiwan. We report the decline of S. enterica Choleraesuis infections coinciding with the implementation of several national control programs in Taiwan. In humans, S. enterica Choleraesuis usually causes invasive infections (1). Transmission of the organism is probably from pigs to humans (3). According to an inspection program conducted by the Council of Agriculture in 2004, illegal slaughter of pigs dying of unidentified diseases and sale of the pork at a reduced price were common in Taiwan and probably were associated with transmission of the organism (4). In Taiwan during 1996–1997, a large epidemic of swine foot-and-mouth disease occurred (5), and consumption of pork decreased substantially. To prevent further spread of that epidemic, the government implemented massive slaughter of infected pigs and a swine vaccination policy (5). Coincidently, in 1996–1998, S. enterica Choleraesuis infections among humans decreased significantly (p<0.001) (2). However, during the following years, infections among humans and antimicrobial drug resistance gradually increased (2). In Taiwan, widespread use of antimicrobial drugs in animals, which might contribute to development of antimicrobial drug resistance in human pathogens, was subsequently reported (6). The Taiwan government took further actions to improve the quality of pig husbandry. In 2002, a live attenuated S. enterica Choleraesuis vaccine (Suisaloral; Impfstoffwerk Dessau-Tornau GmbH, Rosslay, Germany) for pigs was licensed for importation (veterinary drug license no. 06387) (7). In 2004, the following approaches were implemented to consolidate the management of animal husbandry and ensure the quality and safety of meat: improving pollution control and sanitary conditions in pig farms by periodic inspection and education programs; implementing regulations to promote and improve an existing quality food certification system, Certified Agricultural Standards, by tracking and auditing illicit labeling; reinforcing monitoring and tracking systems for the sale and consumption of antimicrobial drugs for animal use (by continuing education and inspections with or without fixed schedules); preventing illegal slaughtering and sale of pigs dying of unidentified diseases (by inspections and monetary penalties for violations); and establishing a Taiwan Agriculture and Food Traceability system (http://taft.coa.gov.tw) to fully record all processes from farm to table (4,8). A particularly notable control measure launched at that time was a death insurance program for pigs. Although farmers were fully compensated for their losses, pigs dying of unidentified diseases were collected and chemically marked to prevent the possibility of subsequent illegal use (4). In 2005, 2 representative counties in central-southern Taiwan tried the program. During the next year, the program was extended to 8 neighboring counties, and in 2007, it was implemented in all counties (9). Furthermore, since the establishment of the Taiwan Agriculture and Food Traceability system, various Taiwan Good Agricultural Practice manuals have been gradually developed, and in 2008, a manual for pig farming established official standard operating procedures (10). The control measures seem to be successful, as evidenced by the results of a long-term monitoring program at the 2 large tertiary care hospitals in northern and southern Taiwan (Figure). S. enterica Choleraesuis infections have declined significantly since 2005 in southern Taiwan (Figure, panel A) and since 2006 in northern Taiwan (Figure, panel B) (χ2 test for trend, p 80 in 2004–2005 to 24 in 2006 (Figure, panel B), when the death insurance program was expanded to more areas. At both hospitals, the annual number of S. enterica Choleraesuis infections had decreased consistently in the subsequent years; since 2008, this number has remained <10 (Figure). Figure Trends of annual numbers and percentages of Salmonella enterica serotype Choleraesuis isolates from 2 tertiary care hospitals in Taiwan. A) Data from Chang Gung Memorial Hospital at Kaohsiung, southern Taiwan. B) Data from Chang Gung Memorial Hospital ... After interruption of the identified infection chain, the substantial decline of infection among humans became evident. Despite the absence of national surveillance data for nontyphoid human salmonellosis in Taiwan, the decrease in S. enterica Choleraesuis infections reported herein has also been noted at other hospitals in Taiwan (L.-H. Su, pers. comm.). This finding demonstrates that application of effective control measures on farms and in agricultural practices can lead to successful control of S. enterica Choleraesuis infection among humans.

Comment on: The national burden of infections after prostate biopsy in England and Wales: a wake-up call for better prevention

Transrectal ultrasound-guided needle biopsies (TGBs) are the mainstayof prostate cancer diagnosis. An averageof 72500 TGBs were performed in England and Wales in 2008. Current guidelines recommend fluoroquinoloneprophylaxis for TGBs. However, emerging fluoroquinolone resistance has led to increased frequency and mor-bidity due to post-TGB infections. Following TGB, 2.15%–3.6% of patients are readmitted with infective com-plications. We estimate readmissions result in 25745–37062 bed days at an annual cost of £7.7–11.1million in England and Wales. Clearly, an increase in post-TGB infections with resistant organisms has a pro-found clinical and economic impact. We suggest alternative approaches to prophylaxis to reduce post-TGBinfections. These include prophylaxis based on local antibiotic resistance surveillance and targeted prophylaxisbased on antibiograms of coliforms detected in pre-biopsy rectal swabs. Other strategies include selective pros-tate-specific antigen (PSA) screening and the use of biomarkers like prostate cancer antigen 3 (PCA3) to reducethe number of TGBs. Furthermore, transperineal biopsy has been shown to be associated with fewer infections.Keywords: prostate cancer, healthcare-associated infections, healthcare costs, ciprofloxacin resistance, antimicrobial prophylaxis,harm limitation

A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic

The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalized patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with health care. The most rapidly spreading and tenacious health-care-associated clone in Europe currently is EMRSA-15, which was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. Using phylogenomic methods to analyze the genome sequences for 193 S. aureus isolates, we were able to show that the current pandemic population of EMRSA-15 descends from a health-care-associated MRSA epidemic that spread throughout England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 subclone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this subclone over the last 20 yr has grown four times faster than its progenitor. Using comparative genomic analysis we identified the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens.