Antimicrobial use: a risk factor or a protective factor for acquiring campylobacteriosis?

BACKGROUND: It is well acknowledged that the use of antimicrobial drugs in food animals leads to antimicrobial drug resistance in foodborne bacteria such as Campylobacter; however, the role of human antimicrobial usage is much less investigated. The aim of this study was to quantify the odds of campylobacteriosis conferred by human consumption of fluoroquinolones and macrolides. METHODS: We conducted a registry-based retrospective case-control study on 31 669 laboratory-confirmed cases of campylobacteriosis between 1999 and 2005 in Denmark. Data were obtained from several Danish databases: the National Registry of Enteric Pathogens, the Danish Civil Registration System, the Danish National Prescription Database, and the Integrated Database on Labor Market Research. Odds ratios (OR) for campylobacteriosis were calculated by conditional logistic regression. RESULTS: The risk of campylobacteriosis was reduced 1 month after exposure to macrolides (OR, 0.72; 95% confidence interval [CI], 0.56-0.92). Macrolide exposure 1 month to 2 years before infection was associated with an increased risk of a Campylobacter diagnosis (OR, 1.5; 95% CI, 1.4-1.6). A history of fluoroquinolone use was also associated with increased risk (OR, 2.5; 95% CI, 1.8-3.5). This risk was higher for resistant isolates than for susceptible ones. CONCLUSIONS: Treatment with macrolides may protect against Campylobacter infection for a limited period of time, possibly due to the antibacterial effects of the drug or its metabolites. Fluoroquinolone treatment confers increased risk, probably due to a combination of competitive and selective effects, similar to what has been observed for nontyphoid Salmonella infection.

The interaction between prior antimicrobial drug exposure and resistance in human Salmonella infections.

OBJECTIVES: The use of antimicrobial drugs for food animals selects for resistant non-typhoid Salmonella strains, but human consumption of antimicrobial drugs may also increase the risk of subsequent infection. The aim of this study was to determine the risk of salmonellosis attributable to human consumption of antimicrobial drugs in a case-control study of 22 602 laboratory-confirmed Salmonella infections, diagnosed in Denmark between 1997 and 2005. METHODS: A population registry-based case-control study, using several Danish databases: the National Prescription Database; the National Registry for Enteric Pathogens; the Civil Registry System; and the Integrated Database on Labour Market Research. RESULTS: Exposure to trimethoprim, sulphonamides, broad-spectrum penicillins, tetracyclines and fluoroquinolones, during the year prior to diagnosis, was associated with an increased risk of non-typhoid Salmonella infection. Overall, the highest risk was associated with the prior use of fluoroquinolones. This risk increased as the time window of exposure approached the infection date. Previous use of fluoroquinolones was associated with an odds ratio (OR) of 4.55 [95% confidence interval (CI): 3.78-5.47] for Salmonella serotypes other than Salmonella Typhimurium or Salmonella Enteritidis, an OR of 2.21 (95% CI: 1.70-2.86) for Salmonella Typhimurium and an OR of 2.07 (95% CI: 1.76-2.42) for Salmonella Enteritidis. In particular for fluoroquinolones, there was an interaction between the pathogen resistance pattern and a history of antibiotic drug use. CONCLUSIONS: The increasing use of antibiotics, particularly fluoroquinolones, is likely to result in increased incidence of foodborne infections with drug-resistant Salmonella.

Prevalence and Risk Factors for Colonization With Extended-Spectrum Cephalosporin-Resistant Escherichia coli in Children Attending Daycare Centers: A Cohort Study in the Netherlands.

BACKGROUND: The purpose of this study was to determine the prevalence and risk factors for colonization with extended-spectrum cephalosporin-resistant (ESC-R) Escherichia coli in daycare center (DCC)-attending children. METHODS: This is a prospective cohort study including 44 DCCs in the Netherlands, combining DCC characteristics and monthly collected stool samples from their attendees, and was performed in 2010-2012. During a 22-month study period, 852 stool samples were collected and screened for ESC-R E coli. Risk factors were studied using logistic regression analysis. RESULTS: In DCC-attending children (<4 years old), the overall prevalence of ESC-R E coli was 4.5%, and it was 8% in <1-year-old attendees. Among the 38 children carrying ESC-R E coli, the most common types were blaCMY-2 (26%), blaCTX-M-1 (16%), and chromosomal AmpC type 3 promoter mutants (13%). Extended-spectrum cephalosporin-resistant E coli was less common in DCCs where stricter hygiene protocols were enforced, eg, not allowing ill children to enter the DCC (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.14-0.84), performing extra checks on handwashing of ill children (OR, 0.42; 95% CI, 0.20-0.87), and reporting suspected outbreaks to local health authorities (OR, 0.27; 95% CI, 0.11-0.69). CONCLUSIONS: The distribution of ESC-R E coli types in DCCs differs from that of the general population. Extended-spectrum cephalosporin-resistant E coli carriage in DCC-attending children is associated with the hygiene policies enforced in the DCC. Although our results are not conclusive enough to change current DCC practice beyond ensuring compliance with standing policies, they generated hypotheses and defined the degree of ESC resistance among DCC attendees, which may influence empiric antibiotic therapy choices, and tracked the increasing trend in ESC resistance.

Recommendations for the empirical treatment of complicated urinary tract infections using surveillance data on antimicrobial resistance in the Netherlands.

BACKGROUND: Complicated urinary tract infections (c-UTIs) are among the most common nosocomial infections and a substantial part of the antimicrobial agents used in hospitals is for the treatment of c-UTIs. Data from surveillance can be used to guide the empirical treatment choices of clinicians when treating c-UTIs. We therefore used nation-wide surveillance data to evaluate antimicrobial coverage of agents for the treatment of c-UTI in the Netherlands. METHODS: We included the first isolate per patient of urine samples of hospitalised patients collected by the Infectious Disease Surveillance Information System for Antibiotic Resistance (ISIS-AR) in 2012, and determined the probability of inadequate coverage for antimicrobial agents based on species distribution and susceptibility. Analyses were repeated for various patient groups and hospital settings. RESULTS: The most prevalent bacteria in 27,922 isolates of 23,357 patients were Escherichia coli (47%), Enterococcus spp. (14%), Proteus mirabilis (8%), and Klebsiella pneumoniae (7%). For all species combined, the probability of inadequate coverage was <5% for amoxicillin or amoxicillin-clavulanic acid combined with gentamicin and the carbapenems. When including gram-negative bacteria only, the probability of inadequate coverage was 4.0%, 2.7%, 2.3% and 1.7%, respectively, for amoxicillin, amoxicillin-clavulanic acid, a second or a third generation cephalosporin in combination with gentamicin, and the carbapenems (0.4%). There were only small variations in results among different patient groups and hospital settings. CONCLUSIONS: When excluding Enterococcus spp., considered as less virulent, and the carbapenems, considered as last-resort drugs, empirical treatment for c-UTI with the best chance of adequate coverage are one of the studied beta-lactam-gentamicin combinations. This study demonstrates the applicability of routine surveillance data for up-to-date clinical practice guidelines on empirical antimicrobial therapy, essential in patient care given the evolving bacterial susceptibility.

The use of typing methods and infection prevention measures to control a bullous impetigo outbreak on a neonatal ward.

BACKGROUND: We describe an outbreak of Bullous Impetigo (BI), caused by a (methicillin susceptible, fusidic acid resistant) Staphylococcus aureus (SA) strain, spa-type t408, at the neonatal and gynaecology ward of the Jeroen Bosch hospital in the Netherlands, from March-November 2011. METHODS: We performed an outbreak investigation with revision of the hygienic protocols, MSSA colonization surveillance and environmental sampling for MSSA including detailed typing of SA isolates. Spa typing was performed to discriminate between the SA isolates. In addition, Raman-typing was performed on all t408 isolates. RESULTS: Nineteen cases of BI were confirmed by SA positive cultures. A cluster of nine neonates and three health care workers (HCW) with SA t408 was detected. These strains were MecA-, PVL-, Exfoliative Toxin (ET)A-, ETB+, ETAD-, fusidic acid-resistant and methicillin susceptible. Eight out of nine neonates and two out of three HCW t408 strains yielded a similar Raman type. Positive t408 HCW were treated and infection control procedures were reinforced. These measures stopped the outbreak. CONCLUSIONS: We conclude that treatment of patients and HCW carrying a predominant SA t408, and re-implementing and emphasising hygienic measures were effective to control the outbreak of SA t408 among neonates.