Lessons learnt during 20 years of the Swedish strategic programme against antibiotic resistance.

Increasing use of antibiotics and rising levels of bacterial resistance to antibiotics are a challenge to global health and development. Successful initiatives for containing the problem need to be communicated and disseminated. In Sweden, a rapid spread of resistant pneumococci in the southern part of the country triggered the formation of the Swedish strategic programme against antibiotic resistance, also known as Strama, in 1995. The creation of the programme was an important starting point for long-term coordinated efforts to tackle antibiotic resistance in the country. This paper describes the main strategies of the programme: committed work at the local and national levels; monitoring of antibiotic use for informed decision-making; a national target for antibiotic prescriptions; surveillance of antibiotic resistance for local, national and global action; tracking resistance trends; infection control to limit spread of resistance; and communication to raise awareness for action and behavioural change. A key element for achieving long-term changes has been the bottom-up approach, including working closely with prescribers at the local level. The work described here and the lessons learnt could inform countries implementing their own national action plans against antibiotic resistance.

L'utilisation croissante d'antibiotiques et l'augmentation de la résistance bactérienne aux antibiotiques constituent un défi pour le développement et la santé mondiaux. Il est nécessaire de communiquer et de diffuser les initiatives qui parviennent à contenir ce problème. En Suède, la propagation rapide de pneumocoques résistants dans le sud du pays en 1995 a conduit à la formation du Programme stratégique suédois contre la résistance aux antibiotiques, également connu sous le nom de Strama. La création de ce programme a été un point de départ important pour coordonner des efforts sur le long terme afin de lutter contre la résistance aux antibiotiques dans le pays. Cet article décrit les principales stratégies du programme: engagement aux niveaux local et national; suivi de l'utilisation d'antibiotiques afin de prendre des décisions en connaissance de cause; objectif national de prescription d'antibiotiques; surveillance de la résistance aux antibiotiques pour agir au niveau local, national et mondial; observation des tendances de résistance; lutte contre les infections afin de limiter la progression de la résistance; communication afin d'inciter à l'action et au changement des comportements. L'adoption d'une démarche ascendante a été un élément clé pour favoriser les changements à long terme, notamment la collaboration étroite avec les prescripteurs au niveau local. Le travail qui est décrit ici et les enseignements tirés pourraient aider les pays à mettre en œuvre leur propre plan d'action national contre la résistance aux antibiotiques.

El creciente uso de antibióticos y el aumento de los niveles de resistencia bacteriana a los antibióticos son un desafío para la salud y el desarrollo mundiales. Es necesario comunicar y difundir iniciativas de éxito para contener el problema. En Suecia, una rápida propagación de neumococos resistentes en el sur del país desencadenó la formación del programa estratégico sueco contra la resistencia a los antibióticos, también conocido como Strama, en 1995. La creación del programa fue un importante punto de partida de los esfuerzos coordinados a largo plazo para combatir la resistencia a los antibióticos en el país. En este artículo se describen las principales estrategias del programa: labores dedicadas a nivel local y nacional, supervisión del uso de antibióticos para tomar decisiones fundamentadas, un objetivo nacional para las recetas de antibióticos, vigilancia de la resistencia a los antibióticos para la acción local, nacional y global; seguimiento de las tendencias de resistencia, control de las infecciones para reducir la propagación de la resistencia y comunicación para sensibilizar sobre las medidas y el cambio de comportamiento. Un elemento clave para conseguir cambios a largo plazo ha sido en enfoque ascendente, que incluye trabajar estrechamente con los médicos a nivel local. El trabajo aquí descrito y las lecciones aprendidas podrían ofrecer información a los países que implementan sus propios planes de medidas nacionales contra la resistencia a los antibióticos.

A randomized controlled study of 5 and 10 days treatment with phenoxymethylpenicillin for pharyngotonsillitis caused by streptococcus group A - a protocol study.

BACKGROUND: In 2014 the Swedish government assigned to The Public Health Agency of Sweden to conduct studies to evaluate optimal use of existing antibiotic agents. The aim is to optimize drug use and dosing regimens to improve the clinical efficacy. The present study was selected following a structured prioritizing process by independent experts. METHODS: This phase IV study is a randomized, open-label, multicenter study with non-inferiority design regarding the therapeutic use of penicillin V with two parallel groups. The overall aim is to study if the total exposure with penicillin V can be reduced from 1000 mg three times daily for 10 days to 800 mg four times daily for 5 days when treating Streptococcus pyogenes (Lancefield group A) pharyngotonsillitis. Patients will be recruited from 17 primary health care centers in Sweden. Adult men and women, youth and children ≥6 years of age who consult for sore throat and is judged to have a pharyngotonsillitis, with 3-4 Centor criteria and a positive rapid test for group A streptococci, will be included in the study. The primary outcome is clinical cure 5-7 days after discontinuation of antibiotic treatment. Follow-up controls will be done by telephone after 1 and 3 months. Throat symptoms, potential relapses and complications will be monitored, as well as adverse events. Patients (n = 432) will be included during 2 years. DISCUSSION: In the era of increasing antimicrobial resistance and the shortage of new antimicrobial agents it is necessary to revisit optimal usage of old antibiotics. Old antimicrobial drugs are often associated with inadequate knowledge on pharmacokinetics and pharmacodynamics and lack of optimized dosing regimens based on randomized controlled clinical trials. If a shorter and more potent treatment regimen is shown to be equivalent with the normal 10 day regimen this can imply great advantages for both patients (adherence, adverse events, resistance) and the community (resistance, drug costs). TRIAL REGISTRATION: EudraCT number 2015-001752-30 . Protocol FoHM/Tonsillit2015 date 22 June 2015, version 2. Approved by MPA of Sweden 3 July 2015, Approved by Regional Ethical Review Board in Lund, 25 June 2015.

Repeated nationwide point-prevalence surveys of antimicrobial use in Swedish hospitals: data for actions 2003-2010.

This study sought to analyse antimicrobial pressure, indications for treatment, and compliance with treatment recommendations and to identify possible problem areas where inappropriate use could be improved through interventions by the network of the local Swedish Strategic Programme Against Antibiotic Resistance (Strama) groups. Five point-prevalence surveys were performed in between 49 and 72 participating hospitals from 2003 to 2010. Treatments were recorded for 19 predefined diagnosis groups and whether they were for community-acquired infection, hospital-acquired infection, or prophylaxis. Approximately one-third of inpatients were treated with antimicrobials. Compliance with guidelines for treatment of community-acquired pneumonia with narrow-spectrum penicillin was 17.0% during baseline 2003-2004, and significantly improved to 24.2% in 2010. Corresponding figures for quinolone use in uncomplicated cystitis in women were 28.5% in 2003-2004, and significantly improved, decreasing to 15.3% in 2010. The length of surgical prophylaxis improved significantly when data for a single dose and 1 day were combined, from 56.3% in 2003-2004 to 66.6% in 2010. Improved compliance was possibly the effect of active local feedback, repeated surveys, and increasing awareness of antimicrobial resistance. Strama groups are important for successful local implementation of antimicrobial stewardship programs in Sweden.

Changes in patterns of antibiotic use in Chinese public hospitals (2005-2012) and a benchmark comparison with Sweden in 2012.

Changes in patterns of antibiotic use in Chinese hospitals before and after intensive nationwide interventions are reported and compared with Chinese national targets and antibiotic use in Swedish hospitals. Chinese data were collected quarterly and yearly from selected patient prescriptions/medical records and medicines inventory control systems from 15 hospitals (2005-2012). Swedish data were extracted from a 2010-point prevalence survey and 2009-2012 sales data from seven university hospitals. An interrupted time series with segmented regression analysis was used to measure changes in patterns of antibiotic use in Chinese hospitals before and after the interventions. Following the 2011 interventions, significant reductions in antibiotic use in Chinese hospitals were seen: the proportion of prescriptions with antibiotics decreased 4.7% (P=0.03) and the proportion of medical records with antibiotic prescription decreased 7.3% (P=0.04). The proportions of prescriptions and medical records with antibiotics in Chinese hospitals in 2012 were 10% and 50%, respectively, and remained much higher than Swedish hospitals (1.1% in DDD for outpatients and 34% in number of patients for inpatients). Inpatient consumption in Chinese hospitals dropped significantly from 910 DDD/1000 inpatient days in 2008 to 473 in 2012 (588 in Swedish hospitals). Antibiotics are being used less frequently in Chinese hospitals, broad-spectrum antibiotics are still preferred, and overall usage is higher than Sweden. A significant reduction in overall inpatient antibiotic consumption was observed after the interventions. It is not possible to identify whether the changes have resulted in less inappropriate antibiotic use. Further studies are needed.

Antibiotic consumption and antibiotic stewardship in Swedish hospitals.

BACKGROUND: The aim of this paper was to describe and analyze the effect of antibiotic policy changes on antibiotic consumption in Swedish hospitals and to review antibiotic stewardship in Swedish hospitals. RESULTS: The main findings were: 1) Antibiotic consumption has significantly increased in Swedish hospitals over the last decade. The consumption of cephalosporins has decreased, whereas that of most other drugs including piperacillin-tazobactam, carbapenems, and penicillinase-sensitive and -resistant penicillins has increased and replaced cephalosporins. 2) Invasive infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae have increased, but the proportion of pathogens resistant to third-generation cephalosporins causing invasive infections is still very low in a European and international perspective. Furthermore, the following gaps in knowledge were identified: 1) lack of national, regional, and local data on the incidence of antibiotic resistance among bacteria causing hospital-acquired infections e.g. bloodstream infections and hospital-acquired pneumonia-data on which standard treatment guidelines should be based; 2) lack of data on the incidence of Clostridium difficile infections and the effect of change of antibiotic policies on the incidence of C. difficile infections and infections caused by antibiotic-resistant pathogens; and 3) lack of prospective surveillance programs regarding appropriate antibiotic treatment, including selection of optimal antimicrobial drug regimens, dosage, duration of therapy, and adverse ecological effects such as increases in C. difficile infections and emergence of antibiotic-resistant pathogens. CONCLUSIONS: Evidence-based actions to improve antibiotic use and to slow down the problem of antibiotic resistance need to be strengthened. The effect of such actions should be analyzed, and standard treatment guidelines should be continuously updated at national, regional, and local levels.

Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial.

BACKGROUND: Acute pyelonephritis is a common infection in adult women, but there is a paucity of controlled trials of its treatment and the optimum duration of antibiotic treatment has not been properly defined. We compared the efficacy of ciprofloxacin for 7 days and 14 days in women with community-acquired acute pyelonephritis. METHODS: In a prospective, non-inferiority trial undertaken at 21 centres of infectious diseases in Sweden, women (aged ≥18 years) who were not pregnant and had a presumptive diagnosis of acute pyelonephritis were randomly assigned to oral treatment with ciprofloxacin 500 mg twice daily for 7 days or 14 days. The first week was open label. A computer-generated randomisation list in block sizes of two was used for treatment allocation in a 1:1 ratio. The study was double-blind and placebo-controlled during the second week of treatment, which was either continuation of ciprofloxacin 500 mg or placebo tablets twice daily according to the randomisation code. Patients, carers, site investigators, and trial coordinating centre staff were masked to group assignment. The primary endpoint was the clinical and bacteriological outcome 10-14 days after completion of treatment with active drug. Analysis was by per protocol. This trial is registered with EudraCT, number 2005-004992-39, and ClinicalTrials.gov, number ISRCTN73338924. FINDINGS: 126 of 248 patients were randomly assigned to 7 days and 122 to 14 days of ciprofloxacin. 73 and 83 patients, respectively, were analysed. Short-term clinical cure occurred in 71 (97%) patients treated with ciprofloxacin for 7 days and 80 (96%) treated for 14 days (difference -0·9%; 90% CI -6·5 to 4·8; p=0·004; non-inferiority test). Cumulative efficacy at long-term follow-up was 93% in each group (68 of 73 vs 78 of 84; -0·3%; -7·4 to 7·2; p=0·015). Both regimens were well tolerated. Two patients discontinued ciprofloxacin because of myalgia with 7 days of treatment and itching exanthema with 14 days. Four (5%) of 86 patients assigned to 7 days of treatment who complied with study criteria and six (6%) of 93 assigned to 14 days reported an adverse event after the first week of treatment that was possibly or probably related to the study drug. In those assigned to 7 days, no patient had mucosal candida infection after the first week versus five treated for 14 days (p=0·036). INTERPRETATION: Our results show that acute pyelonephritis in women, including older women and those with a more severe infection, can be treated successfully and safely with oral ciprofloxacin for 7 days. Short courses of antibiotics should be favoured in an era of increasing resistance. FUNDING: Swedish Strategic Programme against Antibiotic Resistance (Strama).

Antibiotic use and Escherichia coli resistance trends for quinolones and cotrimoxazole in Sweden.

Resistance rates among Escherichia coli isolates for quinolones and cotrimoxazole were analysed at 12 Swedish hospitals, and compared with antibiotic use. Resistance figures for E. coli were retrieved from the diagnostic microbiology service databases for the period 1989-99, and antibiotic sales figures were obtained from the National Corporation of Swedish Pharmacies. At the 2 university teaching hospitals included, norfloxacin resistance of E. coli increased significantly (p < 0.001) from 0% to 2.7% and 2.5%, respectively. Ciprofloxacin resistance increased (p < 0.001) in parallel. Quinolone use increased until 1992; subsequently, sales have remained at a stable level. The increase in norfloxacin and ciprofloxacin resistance started relatively simultaneously in all hospitals, around 1991. Cotrimoxazole resistance has also been increasing significantly in most hospitals, in spite of decreasing sales of cotrimoxazole and trimethoprim. Similar trends could be seen in blood isolates from the same hospitals for the period 1991-98. Clinical laboratory data are subject to bias but surveillance over longer periods of time provides a useful method for detecting trends in increasing resistance and therefore functions as a resistance warning system.