Sustained reduction of antibiotic use and low bacterial resistance: 10-year follow-up of the Swedish Strama programme.

Increasing use of antibiotics and the spread of resistant pneumococcal clones in the early 1990s alarmed the medical profession and medical authorities in Sweden. Strama (Swedish Strategic Programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance) was therefore started in 1994 to provide surveillance of antibiotic use and resistance, and to implement the rational use of antibiotics and development of new knowledge. Between 1995 and 2004, antibiotic use for outpatients decreased from 15.7 to 12.6 defined daily doses per 1000 inhabitants per day and from 536 to 410 prescriptions per 1000 inhabitants per year. The reduction was most prominent in children aged 5-14 years (52%) and for macrolides (65%). During this period, the number of hospital admissions for acute mastoiditis, rhinosinusitis, and quinsy (peritonsillar abscess) was stable or declining. Although the epidemic spread in southern Sweden of penicillin-resistant Streptococcus pneumoniae was curbed, the national frequency increased from 4% to 6%. Resistance remained low in most other bacterial species during this period. This multidisciplinary, coordinated programme has contributed to the reduction of antibiotic use without measurable negative consequences. However, antibiotic resistance in several bacterial species is slowly increasing, which has led to calls for continued sustained efforts to preserve the effectiveness of available antibiotics.

Clonality among ampicillin-resistant Enterococcus faecium isolates in Sweden and relationship with ciprofloxacin resistance.

OBJECTIVE: To investigate clonal relationships in a nationwide sample of human Enterococcus faecium isolates. METHODS: Biochemical fingerprinting (PhP (PhenePlate) typing) was used to compare 180 fecal ampicillin-resistant E. faecium (ARE) isolates with 169 matched fecal ampicillin-susceptible E. faecium (ASE) isolates from patients in 23 hospitals, collected in 1998, and to study 39 fecal ARE isolates from non-hospitalized individuals collected in 1998, and five ARE and 29 ASE isolates from the early 1990s. Representative ARE and ASE isolates were subjected to pulsed-field gel electrophoresis (PFGE) analysis of genomic DNA and sequencing of the regions encoding the fluoroquinolone targets of the enzymes GyrA and ParC. RESULTS: Both PhP and PFGE results showed a higher homogeneity among ARE than among ASE isolates (P < 0.001). One PhP type (FMSE1) comprised 73% of the hospital ARE isolates (53% of ARE isolates from non-hospitalized individuals, and four of five ARE isolates from the early 1990s), but only 1% of the ASE isolates. PFGE of the hospital E. faecium isolates revealed that 23 of the 25 ARE isolates and one of the 22 ASE isolates were of one dominating type. High-level resistance to ciprofloxacin (MIC > 16 mg/L) was present in 91% of ARE isolates, whereas only low-level resistance (MIC 4-16 mg/L; 35% of isolates) was found among ASE isolates. One mutation in parC (codon 80) and one of two mutations in gyrA (codons 83 or 87) were detected in all ARE isolates tested with high-level ciprofloxacin resistance, but were lacking in ARE and ASE isolates with low-level ciprofloxacin resistance. CONCLUSION: Most ARE isolates in Sweden were clonally related. High-level ciprofloxacin resistance was found in ARE isolates of PhP type FMSE1 as well as in other PhP types, but never in ASE isolates.

Prevalence of resistance to ampicillin, gentamicin and vancomycin in Enterococcus faecalis and Enterococcus faecium isolates from clinical specimens and use of antimicrobials in five Nordic hospitals.

We determined the species distribution and prevalence of ampicillin resistance, high-level gentamicin resistance (HLGR) and vancomycin resistance among clinical enterococcal isolates from five Nordic laboratories (Bergen, Tromsø, Uppsala, Aarhus and Reykjavik). Isolates represented three different groups: (i) all blood culture isolates from 1999; (ii) consecutive in-patient isolates (maximum 40); and (iii) consecutive outpatient isolates (maximum 40) collected during March to May 2000. Antimicrobial use data were collected at the national and hospital level. A high proportion (31.4%) of Enterococcus faecium was detected among blood culture isolates, in contrast to only 4.2% among isolates from outpatients. Ampicillin resistance was not found in Enterococcus faecalis, in contrast to 48.8% in E. faecium isolates. HLGR rates varied considerably between laboratories (1.1-27.6%). Acquired vancomycin resistance was not detected. There were no significant differences in the prevalences of HLGR between in-patient and outpatient isolates at individual hospitals. A cluster of clonally related ampicillin-resistant and HLGR E. faecium isolates was demonstrated in one of the hospitals. The lowest level of hospital antimicrobial use, the lowest proportion of E. faecium and the lowest prevalence of resistance were observed in Reykjavik. The study showed a relatively low level of resistance in enterococci, as compared with most European countries and the USA. However, there were large differences between hospitals with regard to the relative proportion of E. faecium isolates, their susceptibility to ampicillin and gentamicin, as well as the prevalence of HLGR in E. faecalis isolates. This indicates a potential for further improvement of antibiotic policies, and possibly hospital infection control, to maintain the low resistance levels observed in these countries.

Ampicillin-resistant enterococci in a Swedish university hospital: nosocomial spread and risk factors for infection.

Ampicillin-resistant enterococci (ARE) have recently emerged as clinical pathogens in Sweden. Between 1991 and 1995 the incidence of ARE among enterococcal isolates at Uppsala University Hospital increased from 0.5% to 8.1%. Shedding of ARE from infected cases and risk factors for infection with ARE were studied during a period of 7 months for 38 ARE cases and 38 controls with ampicillin-susceptible enterococci. ARE cases had longer mean duration of hospitalization than controls (29 d vs. 15 d; p = 0.002). In univariate analysis other risk factors for infection with ARE were found to be prior therapy with > 2 antimicrobials (odds ratio [OR] 3.3; 95% confidence interval [CI] 1.2-9.5), > 4 weeks of antimicrobial therapy (OR 6.9; CI 1.8-28.3) and cephalosporin therapy (OR 9.1; CI 2.6-33.7). Fourteen of 26 skin carriers of ARE were found to be shedding ARE to the environment, compared to 2 of 12 non-skin carriers (p = 0.03). Pulsed-field gel electrophoresis suggested multifocal origin of the majority of the infecting ARE strains. Non-recognized fecal colonization and silent spread of ARE among many patients and over a prolonged time period is suggested to be the main explanation for the increase of ARE infections in our hospital. Infection control measures focusing on protecting patients at high risk for ARE infections and further efforts to optimize antimicrobial use are proposed.

Near absence of vancomycin-resistant enterococci but high carriage rates of quinolone-resistant ampicillin-resistant enterococci among hospitalized patients and nonhospitalized individuals in Sweden.

Rates of colonization with enterococci with acquired resistance to vancomycin (vancomycin-resistant enterococci [VRE]) and ampicillin (ampicillin-resistant enterococci [ARE]) were determined by using fecal samples from 670 nonhospitalized individuals and 841 patients in 27 major hospitals. Of the hospitalized patients, 181 (21.5%) were carriers of ARE and 9 (1.1%) were carriers of VRE. In univariate analyses, length of hospital stay (odds ratio [OR], 4.6; 95% confidence interval [CI], 2.5 to 8.9) and antimicrobial therapy (OR, 4.7; 95% CI, 3.3 to 6.7) were associated with ARE colonization, as were prior treatment with penicillins (OR, 3.1; 95% CI, 1.8 to 5. 5), cephalosporins (OR, 2.9; 95% CI, 1.7 to 5.0), or quinolones (OR, 2.7; 95% CI, 1.5 to 4.7). In logistic regression analysis, antimicrobial therapy for at least 5 days was independently associated with ARE carriage (adjusted OR, 3.8; 95% CI, 2.6 to 5.4). Over 90% of the ARE isolates were fluoroquinolone resistant, whereas 14% of the ampicillin-susceptible Enterococcus faecium isolates were fluoroquinolone resistant. ARE carriage rates correlated with the use of fluoroquinolones (P = 0.04) but not with the use of ampicillin (P = 0.68) or cephalosporins (P = 0.40). All nine VRE isolates were E. faecium vanB and were found in one hospital. Seven of these isolates were related according to their types as determined by pulsed-field gel electrophoresis. Among the nonhospitalized individuals, the ARE carriage rate was lower (6%; P < 0.05), and only one person, who had recently returned from Africa, harbored VRE (E. faecium vanA). The absence of VRE colonization in nonhospitalized individuals reflects an epidemiological situation in Sweden radically different from that in countries in continental Europe where glycopeptides have been widely used for nonmedical purposes.

[Three Swedish cases of African tick-bite fever. Can our native Rickettsia species cause disease in humans?]. / Tre svenska fall av "African tick-bite fever". Kan våra inhemska rickettsier ge sjukdom hos människa?

The article consists in a report of three cases of African tick-bite fever in Swedish tourists returning from brief visits to South Africa. The clinical course included eschar, regional lymphadenopathy, fever and, in two cases, maculopapular rash. Two cases were characterised by significant increases in anti-Rickettsia conorii IgG and IgM antibody titres. However, the aetiological agent was assumed to be Rickettsia africae, based on reports by others and the widespread serological cross-reactivity among spotted fever Rickettsia spp. The third case was diagnosed on clinical grounds. During the past ten years, 50 per cent (41/80) of cases diagnosed serologically as rickettsial (R. conorii antigen) spotted fever at the Swedish Institute for Infectious Disease Control were associated with travel to South Africa. Parallels are drawn to the recent finding of R. helvetica in Swedish ticks (Ixodes ricinus), and the possibility of its pathogenicity to humans is discussed, though no such clinical cases have been reported to date.

Intrahospital spread of vancomycin-resistant Enterococcus faecium in Sweden.

During a 17-week period vancomycin-resistant Enterococcus faecium (VRE) was found in clinical specimens from 4 in-patients. All bacterial isolates were phenotypically VanA, showing high-level resistance to vancomycin (MIC 256 micrograms/ml) and teicoplanin (MIC 24-256 micrograms/ml). The corresponding gene (vanA) was detected with PCR in strains from 3 of the patients. Three patients had been hospitalized at the renal unit at Orebro Medical Centre Hospital (OMCH). The fourth patient, diagnosed in another hospital, had received treatment in the oncology unit at OMCH. All patients recovered without treatment specific for VRE. Isolates from 2 patients were indistinguishable by pulsed-field gel electrophoresis of genomic DNA. Genetically, these strains were related to the VRE isolates from the 2 other patients. Screening of hospital staff and other in-patients for gastrointestinal carriage of VRE was negative. Glycopeptide-resistant enterococci have not previously been found in OMCH. No new cases were identified during a 10-month follow-up period. Our cases represent the first nosocomial outbreak of VRE in Sweden.