Reduced dispensing of prescribed antibiotics during the Covid-19 pandemic has not increased severe complications from common infections.

BACKGROUND: Sweden has seen an accelerated decline in the number of dispensed antibiotic prescriptions from an already low level during the Covid-19 pandemic. This prompted us to explore whether the decrease in antibiotic prescriptions has reached a critically low level and resulted in an increase in treatment of severe complications from common infections. The aim was to study if the accelerated decrease in antibiotic sales has led to an increase in complications in outpatients with common infections. METHOD: A population-based nationwide registry study based on the Swedish Prescribed Drug Register and the National Patient Register. RESULTS: The total number of dispensed antibiotic prescriptions decreased by 17% during 2020 compared to 2019. The decrease was most pronounced in younger age groups and for antibiotics targeting respiratory tract infections. The number of hospital admissions and visits to open specialist care due to pneumonia or complications related to otitis, tonsillitis, or sinusitis decreased by 4-44%. Prescriptions and numbers of visits or admissions due to urinary tract infections and skin infections remained largely unchanged compared to previous years. CONCLUSION: No increase in complications due to common bacterial infections could be detected despite an unprecedented decline in dispensed antibiotic prescriptions in outpatient care in 2020. The decrease in dispensed antibiotic prescriptions from pharmacies was probably primarily related to a general decrease in the incidence of respiratory infections due to the recommendations and restrictions implemented to mitigate the Covid-19 pandemic in Sweden. This in return led to fewer doctors' visits and consequently to fewer occasions to prescribe antibiotics, be they warranted or not.

A microsimulation model projecting the health care costs for resistance to antibacterial drugs in Sweden.

BACKGROUND: Previous studies have shown that increasing antibacterial resistance (ABR) globally will cause extensive morbidity, deaths and escalated health care costs. METHODS: To project economic consequences of resistance to antibacterial drugs for the Swedish health care sector, we used an individual-based microsimulation model, SESIM. Health care consumption was represented as increased numbers of hospital days, outpatient visits and contact tracing for individuals getting clinical infections or becoming asymptomatic carriers. The risk of contracting a resistant bacterium was calculated using the incidence of mandatorily notifiable ABR in Sweden. RESULTS: We estimate accumulated additional health care costs attributable to notifiable ABR from 2018 until 2030 to EUR 406 million and EUR 1, 503 million until 2050. Until 2030 the largest proportion, more than EUR 247 million (EUR 958 million until 2050), was due to ESBL, followed by methicillin resistant Staphylococcus aureus, carbapenemase-producing Enterobacteriaceae, vancomycin-resistant Enterococci and penicillin non-susceptible Pneumococci which incurred costs of EUR 128 million (EUR 453 million, 2050), EUR 15 million (EUR 58 million, 2050), EUR 13 million (EUR 28 million, 2050) and EUR 2 million (EUR 6 million, 2050), respectively. CONCLUSIONS: Projections concerning the future costs of ABR can be used to guide priorities and distribution of limited health care resources. Our estimates imply that costs in Sweden will have doubled by 2030 and increased more than 4-fold by 2050 if present trends continue and infection control practices remain unchanged. Still, indirect societal costs and costs for non-notifiable resistance remain to be added.

Antibiotic prescription and clinical management of common infections among general practitioners in Latvia, Lithuania, and Sweden: a pilot survey with a simple protocol.

Comparative information on diagnosis-related antibiotic prescribing patterns are scarce from primary care within and between countries. To describe and compare antibiotic prescription and routine management of infections in primary care in Latvia (LV), Lithuania (LT) and two study sites in Sweden (SE), a cross-sectional observational study on patients who consulted due to sypmtoms compatible with infection was undetraken. Infection and treatment was detected and recorded by physicians only. Data was collected from altogether 8786 consecutive patients with infections in the three countries. Although the overall proportion of patients receiving an antibiotic prescription was similar in all three countries (LV and LT 42%, SE 38%), there were differences in the rate of prescription between the countries depending on the respective diagnoses. While penicillins dominated among prescriptions (LV 58%, LT 67%, SE 70%), phenoxymethylpenicillin was most commonly prescribed in Sweden (57% of all penicillins), while it was amoxicillin with or without clavulanic acid in Latvia (99%) and Lithuania (85%) respectively. Pivmecillinam and flucloxacillin, which accounted for 29% of penicillins in Sweden, were available neither in Latvia nor in Lithuania. The applied methodology was simple, and provided useful information on differences in treatment of common infections in ambulatory care in the absence of available computerized diagnosis-prescription data. Despite some limitations, the method can be used for assessment of intention to treat and compliance to treatment guidelines and benchmarking locally, nationally, or internationally, just as the point prevalence surveys (PPS) protocols have been used in hospitals all over Europe.

High Gastrointestinal Colonization Rate with Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae in Hospitalized Patients: Emergence of Carbapenemase-Producing K. pneumoniae in Ethiopia.

We investigated the gastrointestinal colonization rate and antibiotic resistance patterns of Extended-Spectrum Beta-Lactamase (ESBL)- producing Escherichia coli and Klebsiella pneumoniae in hospitalized patients admitted at Ethiopia's largest tertiary hospital. Fecal samples/swabs from 267 patients were cultured on chrome agar. ESBL. Bacterial species identification, verification of ESBL production and antibiotic susceptibility testing were done using Vitek 2 system (bioMérieux, France). Phenotype characterization of ESBL-E.coli and ESBL- K.pneumoniae was done using Neo-Sensitabs™. ESBL positivity rate was much higher in K. pneumoniae (76%) than E. coli (45%). The overall gastrointestinal colonization rate of ESBL producing Enterobacteriaceae (ESBL-E) in hospitalized patients was 52% (95%CI; 46%-58%) of which, ESBL-E. coli and K.pneumoniae accounted for 68% and 32% respectively. Fecal ESBL-E carriage rate in neonates, children and adults was 74%, 59% and 46% respectively. Gastrointestinal colonization rate of ESBL-E.coli in neonates, children and adults was 11%, 42% and 42% respectively. Of all E. coli strains isolated from adults, children and neonates, 44%, 49% and 22% were ESBL positive (p = 0.28). The prevalence of ESBL-K.pneumoniae carriage in neonates, children and adults was 68%, 22% and 7% respectively. All K. pneumoniae isolated from neonates (100%) and 88% of K. pneumoniae isolated from children were ESBL positive, but only 50% of K.pneumoniae isolated from adults were ESBL positive (p = 0.001). Thirteen patients (5%) were carriers of both ESBL-E.coli and ESBL-KP. The overall carrier rate of ESBL producing isolates resistant to carbapenem was 2% (5/267), all detected in children; three with E.coli HL cephalosporinase (AmpC), resistant to ertapenem and two with K. pneumoniae Carbapenemase (KPC) resistant to meropenem, ertapenem and impenem. We report a high gastrointestinal colonization rate with ESBL-E and the emergence of carbapenems-resistant K. pneumoniae in Ethiopia. Urgent implementation of infection control measures, and surveillance are urgently needed to limit the spread within healthcare facilities and further to the community.

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.

Outbreaks of methicillin-resistant Staphylococcus aureus among staff and dogs in Swedish small animal hospitals.

Methicillin-resistant Staphylococcus aureus (MRSA) was found in a dog for the first time in Sweden in 2006. Between October 2006 and May 2007, MRSA was diagnosed in 7 more dogs that had been treated in 3 different small animal hospitals, located 150-200 km apart, in different counties of Sweden. Screening of the animal hospital staff and environment in these small animal hospitals showed 20 of 152 staff to be positive for MRSA, with rates between 2% and 18% in the different hospitals, while all 128 environmental samples were negative. All MRSA isolates from dogs and staff belonged to spa type t032, were Panton-Valentine leukocidin (PVL)-negative, and had indistinguishable pulsed-field gel electrophoresis patterns, except for 2 isolates with closely related patterns. To our knowledge, this is the first report of multiple outbreaks of MRSA in dogs caused by the same strain within a short time frame, and appearing in a country with low prevalence of MRSA in both humans and dogs. This highlights the importance of infection control programs in animal hospitals and in animal health care. Awareness of MRSA as an occupational risk for veterinary personnel is essential.

A pilot study of risk adjustment for benchmarking antibiotic use between hospitals in Sweden.

There is no established standard for comparing overall antibiotic use between hospitals taking patient characteristics into account. The objective of this study was to investigate whether there is a correlation between surrogate markers for patient morbidity, namely case mix index (CMI), mean length of hospital stay (LoS) and mean cost per admission, and antibiotic use in a sample of Swedish hospitals. All primary and secondary hospitals in three counties with high and three counties with low consumption of antibiotics were selected. Data from 16 hospitals were included. A regression analysis was used to evaluate whether there was a linear trend between defined daily doses (DDD) of antibiotics per 100 bed-days and the surrogate markers for morbidity. No correlation could be found between any of the measures of morbidity and total antibiotic consumption. However, a correlation was found between CMI and the proportion of narrow-spectrum antibiotics: the higher the CMI, the lower the proportional use of ß-lactamase-sensitive penicillins. In conclusion, it was found that CMI, mean LoS and mean cost per admission did not appears to be useful factors to adjust for when comparing antibiotic use in this subset of primary and secondary care hospitals. Based on this limited study, we suggest that DDD/100 bed-days can still be used as an appropriate metric to benchmark antibiotic use in primary and secondary hospitals until a better marker for variation of patients and activities is identified.

Pathogens in the lower respiratory tract of intensive care unit patients: impact of duration of hospital care and mechanical ventilation.

BACKGROUND: Ventilator-associated pneumonia (VAP), the most common hospital-acquired infection in intensive care unit (ICU) patients, is caused by bacteria in the lower respiratory tract of mechanically ventilated patients. METHODS: The current study was focused on 443 bacterial isolates from the lower respiratory tract of mechanically ventilated ICU patients (n = 346) in a Swedish University Hospital. Data were obtained from a prospective infection control database covering 9 y (2002-2010). We analysed the correlation between duration of hospital care and mechanical ventilation at the time of sampling on the occurrence of different pathogens. RESULTS: Duration of hospital care and mechanical ventilation prior to sampling was similarly short for Streptococcus pneumoniae, beta-streptococci, and Haemophilus influenzae (≤ 2 days). In contrast, duration of hospital care and mechanical ventilation were longest for Stenotrophomonas maltophilia (6 and 11 days). For Staphylococcus aureus, the most common Gram-positive isolate, the duration was longer than for S. pneumoniae but shorter than for most Gram-negative bacteria. With the exception of S. maltophilia and Pseudomonas aeruginosa, the median duration of mechanical ventilation was short and similar for most bacteria. In samples taken on the first day of mechanical ventilation, the rate of pathogens expected to be resistant to cefotaxime was 23%. CONCLUSIONS: The occurrence of pathogens with high antibiotic resistance in the lower respiratory tract increases with increased duration of hospital care and mechanical ventilation. An equally important result is that pathogens resistant to third-generation cephalosporins were more common than expected, even after a very short duration of hospital care and mechanical ventilation.

Serologic analysis of returned travelers with fever, Sweden.

We studied 1,432 febrile travelers from Sweden who had returned from malaria-endemic areas during March 2005-March 2008. In 383 patients, paired serum samples were blindly analyzed for influenza and 7 other agents. For 21% of 115 patients with fever of unknown origin, serologic analysis showed that influenza was the major cause.

Fighting antibiotic resistance in Sweden--past, present and future.

Sweden has been in the favorable situation of having limited antibiotic resistance and low antibiotic consumption. When pneumococci with reduced susceptibility to penicillin and methicillin-resistant Staphylococcus aureus emerged during the 1990s, professionals and relevant authorities called for extensive action plans to avoid the critical threshold levels of resistance experienced in other countries. The purpose of this paper is to examine Swedish experiences in light of new and future challenges by reviewing Swedish data on antibiotic resistance and antibiotic use, notifications, outbreak control, action plans and scientific papers. The tradition of liberal performance of clinical cultures, together with well functioning diagnostic laboratories, has formed a basis for close collaboration and development of surveillance within quality assurance programs. For more than 20 years the pharmacy monopoly in Sweden has made it possible to collect well defined data on antibiotic sales at the county level with almost 100% coverage. Multisectorial collaboration was set up in regional Strama (Swedish Strategic Programme Against Antibiotic Resistance) groups. Large diagnosis-prescribing surveys have been undertaken, and the concept of basic hygiene precautions was introduced, together with extensive programs for early case finding. However, surveillance has been hampered by inadequate IT systems and some difficulties in collecting relevant data on antibiotic sales at the national level. Also, a decentralized system with 21 counties and regions has resulted in divergence of action plans and rules. The containment of antibiotic resistance thus far may be explained by the early response in human and veterinary medicine and close multisectorial collaboration, supported by the government, before problems got out of hand. Nevertheless, rapidly growing problems with bacteria that produce extended beta-lactamases have recently emerged and antibiotic sales have started to increase again. The outcome of ongoing revision of legislation and surveillance will have great impact on the future possibilities of limiting antibiotic resistance in Sweden.

ICU stay promotes enrichment and dissemination of multiresistant coagulase-negative staphylococcal strains.

Patients in the intensive care unit (ICU) are prone to be colonized and infected by multi-resistant bacteria. It is previously known that nosocomial infections are often preceded by cross-transmission events. The aim of the present investigation was to study the impact of the patient's length of ICU stay on the resistance patterns, diversity and dissemination of coagulase-negative staphylococci (CoNS) within and between patients. Two groups of patients were studied, including 20 consecutive patients sampled within 2 h from admission (short-stayers, SS), and all patients treated for at least 5 d in the ICU (long-stayers, LS), available for sampling every second week (n = 15). Sampling was performed from 5 sites: oropharynx, nares, neck, axilla and perineum. A total of 868 CoNS isolates deriving from LS patients and 403 isolates from SS patients were analysed for antimicrobial susceptibility, clonal diversity and dissemination within and between patients. The highest resistance rates were seen for oxacillin and ciprofloxacin, being 92% and 83%, respectively. Long-stayers were at significantly higher risk of being colonized with CoNS isolates resistant against oxacillin, clindamycin, ciprofloxacin, gentamicin as well as with multiresistant strains. By genotyping 22 phenotypes that were shared among at least 2 patients, 32 PFGE types of which 16 colonized more than 1 individual were identified. One of the clones was isolated from 10 individuals, including 2 SS patients, indicating an epidemic strain. Prolonged ICU stay was significantly correlated to decreased clonal diversity, increased endogenous dissemination of resistant strains and cross-transmission. The results emphasize the importance of good infection control practice, especially in this vulnerable group of patients.

Molecular epidemiological analysis of Escherichia coli isolates producing extended-spectrum beta-lactamases for identification of nosocomial outbreaks in Stockholm, Sweden.

From June to October of 2002, a cluster of Escherichia coli isolates producing extended-spectrum beta-lactamases (ESBLs) was detected in Stockholm. The isolates were grouped into two clones, one of which had already circulated in the same area before the outbreak. CTX-M-type ESBLs and coresistance to ciprofloxacin were identified in the strains.

Epidemiology and molecular characterization of Clostridium difficile strains from patients with diarrhea: low disease incidence and evidence of limited cross-infection in a Swedish teaching hospital.

We prospectively studied the epidemiology of Clostridium difficile-associated diarrhea (CDAD) in a 900-bed hospital over the course of 12 months by PCR-ribotyping of C. difficile isolates. A total of 304 cases were diagnosed, corresponding to an overall incidence of 7/1,000 admissions, with higher rates in nephrology, hematology, and organ transplantation wards (37, 30, and 21/1,000), and 72% were classified as hospital associated (onset in hospital or onset at home but after a hospital stay within 2 months). All 382 isolates from 227 of 304 (75%) patients available for PCR-ribotyping were typeable, yielding 70 PCR-ribotypes. The three most common types comprised 30% of hospital-associated and 34% of community-associated cases, indicating import via admitted patients as a major source of C. difficile strains occurring in the hospital. Of the 227 patients studied, 38% each contributed 2 to 13 fecal samples positive for C. difficile over the course of the study period. Repeat isolates of the same PCR-ribotype as the first isolate were found in 79% of these patients and in 95% of specimens delivered within 30 days, compared to 63% of those obtained at 31 to 204 days. Nosocomial acquisition of CDAD, defined as the proportion of cases sharing C. difficile type and admitted to the same ward within 2 or 12 months, was 20% and 32% of hospital-associated cases and 14% and 23% of all cases, respectively. Thus, most CDAD cases diagnosed over the course of the study period, including those associated with hospitalization, appeared to be caused by endogenous C. difficile strains rather than by strains truly being acquired in the hospital.