Eva Melander

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.

Duration of Nasopharyngeal Carriage of Penicillin-Resistant Streptococcus pneumoniae: Experiences from the South Swedish Pneumococcal Intervention Project

As a part of an intervention project, all detected carriers of penicillin-resistant pneumococci (PRP) (MIC, > or = 0.5 mg/L) in Malmöhus County, southern Sweden, were followed by means of weekly nasopharyngeal cultures. The median duration of carriage in 678 individuals was 19 days (range, 3-267 days). The duration of carriage was longest in children < 1 year old (median, 30 days) and shortest in adults > 18 years old (median, 14 days). Index cases, whose cultures were performed during an acute infection, were carriers for a mean of 10 days longer than asymptomatic contact cases (P < .05). The PRP spontaneously disappeared from the nasopharynx within 4 weeks in 68%, within 8 weeks in 87%, and within 12 weeks in 94% of the individuals. Other significant risk factors for prolonged carriage were the occurrence of > 6 episodes of acute otitis media (AOM) or first episode of AOM before the age of 1 year (P < .01), the carriage of PRP by other family members (P < .05), and the obtainment of a first positive culture during the winter months (P < .05).

Previous antibiotic consumption and other risk factors for carriage of penicillin-resistant Streptococcus pneumoniae in children.

Abstract As part of the South Swedish Pneumococcal Intervention Project, aimed at reducing the spread of penicillin-resistant pneumococci with MICs for penicillin G≥0.5 mg/l (PRP), all patients in Malmöhus county, southern Sweden, with a culture positive for PRP were followed up by means of repeated nasopharyngeal cultures until PRP-negative. If a child carrying PRP attended a day-care centre, nasopharyngeal cultures were obtained from the other children and staff. All children screened for PRP carriage in 30 day-care centres with an identified index case were included in the analysis, and several outcome variables (antibiotic consumption during the preceding 6 months, previous health and social situation) were assessed in relation to the end-point PRP carriage. Of 1036 children, 128 were found to be PRP carriers and 908 were PRP non-carriers. The PRP carriers had higher antibiotic consumption, were younger and were more often of male sex than the non-carriers (P<0.05). Consumption of antibiotics during the preceding 6 months was noted in 53% of carriers and 45% of non-carriers (relative risk 1.20, 95% confidence interval 1.01–1.43). When adjusting for age, gender and day-care centre attendance, recent consumption of cotrimoxazole (trimethoprim/sulfamethoxazole) emerged as an independent risk factor for PRP-carriage (relative risk 3.48, 95% confidence interval 1.10–11.07). The PRP-carriage rate in three day-care centres with high cotrimoxazole consumption was significantly higher (24%) than in the other day-care centres (10%) (P<0.005). The results indicate that measures aimed at reducing consumption of antibiotics in general, and cotrimoxazole in particular, may decrease the incidence of penicillin resistance, but such measures are, by themselves, probably not sufficient to halt the spread.

Age- and Serogroup-Related Differences in Observed Durations of Nasopharyngeal Carriage of Penicillin-Resistant Pneumococci

ABSTRACT Using data from an ongoing Swedish intervention project, the observed durations of nasopharyngeal carriage of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) (MIC of penicillin G of ≥0.5 μg/ml) stratified by both pneumococcal serogroup and age of the carrier were compared. The means and 95% confidence intervals (CIs) were estimated by fitting a gamma distribution to the observed duration of carriage for each age and serogroup stratum. The mean observed duration of carriage for all cases was 37 days (95% CI, 35 to 38 days). Children below the age of 5 years carried PNSP for significantly longer periods (43 days; 95% CI, 41 to 45 days) compared with older individuals (25 days; 95% CI, 24 to 27 days). There were also differences within the group of cases below the age of 5 years, as the duration of carriage became significantly shorter for each increasing age step: <1, 1 to 2, and 3 to 4 years. In addition, patients <5 years of age carried serogroups 9 and 14 for significantly shorter periods than groups 6 and 23. Serogroup 9 was also carried for significantly shorter periods than group 19. For patients aged 5 years or older, no significant difference in carriage duration for different ages or serogroups could be noted. As young children have the longest duration of PNSP carriage, interventions aiming to reduce the prevalence in this group are of great importance. The results highlight the importance of taking both serogroup and age of the carriers into account when studying the dynamics of pneumococcal transmission in young children.

Frequency of penicillin-resistant pneumococci in children is correlated to community utilization of antibiotics.

OBJECTIVE To study the impact of the utilization of antibiotics in children at the population level on the frequency of penicillin-nonsusceptible pneumococci (PNSP). DESIGN Children ages 0 to 6 years with a nasopharyngeal culture of PNSP were registered on place of residency in the 20 municipalities of the former Malmöhus County (since 1998 a part of Skåne County). Where possible the total number of nasopharyngeal cultures with growth of pneumococci was registered as well. All antibiotic prescriptions for 0- to 6-year-old children were analyzed in the 20 municipalities. MAIN OUTCOME MEASURES Correlation between the utilization of antibiotics and the frequency of PNSP in children at the municipality level. RESULTS The proportion of PNSP among all isolates of pneumococci from nasopharyngeal cultures varied between 0 and 49.5%. The antibiotic utilization in children varied among the 20 neighboring municipalities from 8.5 to 19.7 defined daily doses per 1000 children per day. The municipalities with high total utilization also had more frequent use of macrolides and broad spectrum antibiotics. The was a significant correlation between antibiotic use and the proportion of PNSP (correlation coefficient, 0.96; P = 0.002), and the correlation coefficients for trimethoprim-sulfamethoxazole, amoxicillins, macrolides and cephalosporins were significant at the 0.001 level. There was no significant correlation between the use of penicillin V and the frequency of PNSP. CONCLUSIONS. There was a significant correlation between the frequency of PNSP and the utilization of antibiotics in children at the population level.

Extended-spectrum beta-lactamase-producing Escherichia coli in patients with travellers' diarrhoea.

Abstract The identification of patients carrying extended-spectrum beta-lactamase (ESBL)-producing bacteria is important, since these patients are at risk of receiving inappropriate empirical therapy if they become infected. The purpose of this study was to investigate the occurrence of ESBL-producing bacteria in patients with travellers’ diarrhoea. Patients with travellers’ diarrhoea (N = 242) having delivered stool samples for the diagnosis of Salmonella, Shigella, Yersinia or Campylobacter, were also examined for ESBL-producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. The overall prevalence of faecal carriage of ESBL-producing bacteria was 24% (58/242). Of the patients who had travelled in Europe, 3% (2/63) were found to be ESBL carriers in comparison to 36% (50/138) of those who had travelled outside Europe. ESBL-producing E. coli was especially common among patients returning from India (11/14), Egypt (19/38; 50%) and Thailand (8/38; 22%). In total, 90% of the genes of the ESBL-positive samples were of CTX-M type. The CTX-M-1 group dominated, followed by the CTX-M-9 group. The repetitive sequence-based PCR fingerprint pattern showed that there was no similarity between the ESBL strains found. Patients who have travelled outside Europe are at high risk of being colonized with ESBL-producing Enterobacteriaceae, and, if infected, are also at risk of receiving inappropriate empirical antibiotic therapy.

Prevalence of faecal ESBL carriage in the community and in a hospital setting in a county of Southern Sweden.

The aim of this study was to investigate the prevalence of extended-spectrum beta-lactamase (ESBL)-producing bacteria in patients at various hospital wards and in a group of relatively healthy volunteers, in order to obtain greater knowledge on how common these bacterial strains are in hospital settings and in the general community. Participants (n = 427) were enrolled at a University Hospital and at Primary Health Care Units (PHCUs) in Sweden in 2008 and 2010. The participants provided rectal swabs, which were tested for the occurrence of ESBL-producing bacteria. Positive samples were analysed with polymerase chain reaction (PCR) methods for bacterial strain typing and ESBL phylogroups. In 2008, the prevalence was 2.1% (2/96) in PHCU subjects and 1.8% (2/113) in hospital patients. In 2010, the prevalence was 3.0% (3/100) in PHCU subjects and 6.8% (8/118) in hospital patients. The dominating phylogroups were CTX-M-1 and CTX-M-9. All ESBL-positive isolates were Escherichia coli. We found a higher prevalence of ESBL faecal carriage than expected, both in the hospital setting and in the PHCU group.

Increase of β-Lactam-Resistant Invasive Haemophilus influenzae in Sweden, 1997 to 2010

ABSTRACT The proportions of Haemophilus influenzae resistant to ampicillin and other β-lactam antibiotics have been low in Sweden compared to other countries in the Western world. However, a near-doubled proportion of nasopharyngeal Swedish H. influenzae isolates with resistance to β-lactams has been observed in the last decade. In the present study, the epidemiology and mechanisms of antimicrobial resistance of H. influenzae isolates from blood and cerebrospinal fluid in southern Sweden from 1997 to 2010 (n = 465) were studied. Antimicrobial susceptibility testing was performed using disk diffusion, and isolates with resistance to any tested β-lactam were further analyzed in detail. We identified a significantly increased (P = 0.03) proportion of β-lactam-resistant invasive H. influenzae during the study period, which was mainly attributed to a significant recent increase of β-lactamase-negative β-lactam-resistant isolates (P = 0.04). Furthermore, invasive β-lactamase-negative β-lactam-resistant H. influenzae isolates from 2007 and onwards were found in higher proportions than the corresponding proportions of nasopharyngeal isolates in a national survey. Multiple-locus sequence typing (MLST) of this group of isolates did not completely separate isolates with different resistance phenotypes. However, one cluster of β-lactamase-negative ampicillin-resistant (BLNAR) isolates was identified, and it included isolates from all geographical areas. A truncated variant of a β-lactamase gene with a promoter deletion, blaTEM-1-PΔ dominated among the β-lactamase-positive H. influenzae isolates. Our results show that the proportions of β-lactam-resistant invasive H. influenzae have increased in Sweden in the last decade.

Duration of colonization with extended-spectrum beta-lactamase-producing Escherichia coli in patients with travellers' diarrhoea.

Abstract Background: Resistant Enterobacteriaceae have become a worldwide epidemic during the last decade and are a great threat to health care worldwide. International travel is a major risk factor for becoming colonized with extended-spectrum beta-lactamase (ESBL)-producing bacteria. Data on the persistence of colonization with ESBL-producing bacteria in the faecal flora are limited.Methods: A prospective cohort study was performed between October 2007 and October 2010. Fifty-eight patients with faecal carriage of ESBL-producing Escherichia coli from a previous study of patients with travellers’ diarrhoea were included.Results: Forty-one of the patients had a complete follow-up. Ten of these patients (24%) carried ESBL-producing E. coli at the first follow-up point (3–8 months), of whom 4 had a new ESBL strain. At the 3-y follow-up, 4 patients carried ESBL (10%), of whom 1 had 2 new ESBL strains.Conclusions: The long duration of ESBL carriage is worrisome. These carriers may be an important source of the spread of ESBLs in the population and this has implications for the clinical management of patients.

Duration of methicillin-resistant Staphylococcus aureus colonization after diagnosis: A four-year experience from southern Sweden

Abstract Background: The duration of colonization with methicillin-resistant Staphylococcus aureus (MRSA) is not well known and there is debate as to whether a patient colonized with MRSA ever can be defined as ‘MRSA-negative’. Methods: Since 2003 all notified MRSA cases have been systematically followed in Skåne County, southern Sweden. Cultures are taken from the nares, throat, perineum and possible skin lesions. Contact tracing is conducted. The screening program continues as long as cultures are positive and then until 1 y of consecutive negative cultures for MRSA is completed. Results: Of the 578 MRSA cases during 2003–2006, 535 were included in this retrospective study. The median duration of colonization with MRSA was 5.9 months. Having household contacts with MRSA, young age, spa-type t002 and colonization in 2 or more locations, were significantly associated with a longer duration of colonization. Having a clinical infection treated with antibiotics (compared to clinical infection with no antibiotic treatment or asymptomatic carriage) was significantly associated with a shorter carriage time. Eradication treatment was associated with a shorter carriage time. Conclusion: These results may have implications for the management of patients with MRSA carriage. The study indicates that MRSA carriage can be defined as ‘negative’ in a follow-up program and shows the importance of performing contact tracing among household members.