Penicillin-resistant pneumococci in Sweden : epidemiology and public health response

Since 1996, all identified cases of pneumococci with a MIC for penicillin G > 0.5 mg/L (penicillin resistant pneumococci: PRP) have been registered according to the Swedish Communicable Disease Act. In the same year, an expert committee appointed by the Swedish Board of Health and Welfare presented an intervention programme with the objective to reduce the spread of resistant pneumococci in Sweden. The recommendations included active control measures in day-care centres, as well as actions against inappropriate use of antibiotics. The aim of this thesis was to describe and analyse the epidemiology of reported Swedish PRP cases, and to describe and analyse the public health response aiming to reduce the spread of PRP in the country.

In study I, we describe trends and case characteristics of PRP cases reported according to the Communicable Disease Act between 1997 and 2003. Despite a reduction in the reported PRP incidence by 39 %, the PRP frequency (proportion PRP of all isolated pneumococci) remained stable around 2 % during the period. The reported proportion of PRP resistant to other antibiotics increased, and multi-resistance was common. However, further analysis of PRP case finding activity (study II), indicated that PRP surveillance data might be biased due to both temporal and regional differences in case finding activity. We found that the nasopharyngeal culturing activity was associated with both the pneumococcal and the PRP incidences. Between 1998 and 2003, the reported national nasopharyngeal culturing activity decreased by 31 %. There were also large regional variations, and routines for contact tracing to identify asymptomatic cases differed between the counties. The most common serogroups among reported Swedish PRP cases were in descending order 9, 19, 14, 23 and 6.

In study III, we used data from the South Swedish Pneumococcal Intervention Project to estimate the duration of nasopharyngeal PRP carriage, stratified by both serogroup and age of the case. We found that children below the age of 5 years carried PRP for significantly longer periods (mean 43 days, 95% CI 41-45 days) compared with older individuals (mean 25 days, 95% CI 24 27 days). There were also differences within the group of cases below the age of 5 years, as the observed duration of carriage became significantly shorter for each increasing age-step <1 years, 1-2 years and 3-4 years. In addition, cases aged < 5 years carried serogroup 9 and 14 for significantly shorter periods compared with group 6 and 23. Serogroup 9 was also carried for significantly shorter periods compared with group 19

In study IV, we followed the incidence in day care centre groups with ongoing PRP-spread, to evaluate the effect of temporary excluding PRP carrying children, as recommended by the PRP expert committee. All identified carriers were excluded from day care attendance in study area A (Skåne Region) while they remained in the group in study area B (Göteborg and Örebro), according to existing local policies. The relative risk for children to acquire PRP in DCC groups without active intervention (area B) was 6.4 (95% CI 2.0 - 20.7). Each prevented case in area A was estimated to have demanded the exclusion of 2 other children from day-care for approximately four to five weeks each.

In study V, weekly data on the total number of dispensed outpatient antibiotic prescriptions to children aged < 6 years between 1992 and 2003 were examined by time series analysis. No increasing trend segments could be identifies in data. No correlation could be found between the annual antibiotic sales and the resistance levels of reported PRP between 1998 and 2003 in Study I.

List of scientific papers

I. Hogberg L, Ekdahl K, Sjostrom K, Olsson-Liljequist B, Walder M, Melander E, Ringberg H, Henriques Normark B (2006). Penicillin-resistant pneumococci in Sweden 1997-2003: increased multi-resistance despite stable frequency and decreased antibiotic use. Microbial Drug Resistance. 12(1). [Accepted]
https://doi.org/10.1089/mdr.2006.12.16

II. Hogberg L, Ekdahl K (2006). Sampling bias in the surveeillance of penicillin resistant pneumococci - effects on temporal trends and regional estimates. [Manuscript]

III. Hogberg L, Geli P, Ringberg H, Melander E, Lipsitch M, Ekdahl K (2006). Age and serogroup specific differences in observed duration of nasopharyngeal carriage of penicillin-resistant pneumococci. [Manuscript]

IV. Hogberg L, Henriques Normark B, Ringberg H, Stenqvist K, Fredlund H, Geli P, Grabowska K, Melander E, Laurell M, Ahren C, Tornqvist E, Falt R, Hoglund D, Mollerberg G, Ekdahl K (2004). The impact of active intervention on the spread of penicillin-resistant Streptococcus pneumoniae in Swedish day-care centres. Scand J Infect Dis. 36(9): 629-35.
https://doi.org/10.1080/00365540410022594

V. Hogberg L, Oke T, Geli P, Lundborg CS, Cars O, Ekdahl K (2005). Reduction in outpatient antibiotic sales for pre-school children: interrupted time series analysis of weekly antibiotic sales data in Sweden 1992-2002. J Antimicrob Chemother. 56(1): 208-15.
https://doi.org/10.1093/jac/dki147