Phenotypic and molecular characterizations of carbapenem-resistant Acinetobacter baumannii isolates collected within the EURECA study.

Multi-drug-resistant Acinetobacter baumannii isolates are key pathogens that contribute to the global burden of antimicrobial resistance. This study aimed to investigate the phenotypic and molecular characteristics of carbapenem-resistant A. baumannii (CRAB) isolates from the EURECA clinical trial. In total, 228 CRAB clinical strains were recovered from 29 sites in 10 European countries participating in the EURECA study between May 2016 and November 2018. All strains were reconfirmed centrally for identification and antimicrobial susceptibility testing, and were then subjected to DNA isolation and whole-genome sequencing (WGS), with analysis performed using BacPipe v.1.2.6. K and O typing was performed using KAPTIVE. Overall, 226 (99.1%) strains were confirmed as CRAB isolates. The minimum inhibitory concentration (MIC90) results of imipenem and meropenem were >16 mg/L. WGS showed that the isolates mainly harboured blaOXA-23 (n=153, 67.7%) or blaOXA-72 (n=70, 30.1%). Four blaOXA-72 isolates from Serbia co-harboured blaNDM-1. An IS5 transposase family element, ISAba31, was found upstream of the blaOXA-72 gene harboured on a small (~10-kb) pSE41030-EUR plasmid. The majority of isolates (n=178, 79.1%) belonged to international clone II. Strains belonging to the same sequence type but isolated in different countries or within the same country could be delineated in different clusters by core-genome multi-locus sequence typing (MLST). Whole-genome/core-genome MLST showed high diversity among the isolates, and the most common sequence type was ST2 (n=153, 67.7%). The EURECA A. baumannii strain collection represents a unique, diverse repository of carbapenem-resistant isolates that adds to the existing knowledge of A. baumannii epidemiology and resistance genes harboured by these strains.

Antibiotic use and resistance in Belgium: the impact of two decades of multi-faceted campaigning.

Objective: To present an overview of almost two decades of multi-faceted campaigning by the Belgian Antibiotic Policy Coordination Committee (BAPCOC) and partners, and its impact on public and prescribers' awareness, outpatient antibiotic use, its cost and antimicrobial resistance in Belgium.Methods: Awareness of both public and prescribers was assessed through pre- and post-campaign interviews and surveys. Outpatient antibiotic use was evaluated using national reimbursement data expressed in number of defined daily doses and packages (a good proxy for treatments) per 1000 inhabitants per day (DID and PID, respectively) from July 1997 to June 2018. Its cost was studied using the same data expressed in number of euros per 1000 inhabitants per day. Antimicrobial resistance was evaluated between 1986 and 2017 using national data on the proportion of Streptococcus pneumoniae isolates not susceptible to penicillins, macrolides and tetracyclines.Results: Antibiotic awareness improved significantly, with general practitioners preferred by 87.5% of respondents as source of information. The Belgian outpatient antibiotic use has decreased by 12.8% in DID and by 42.8% in PID in the 2017-2018 winter compared to the winter before the start of its public awareness campaigns (1999-2000). This evolution coincided with decreasing costs for antibiotics and decreasing antimicrobial resistance. Despite multi-faceted campaigning, outpatient antibiotic use and use of broad-spectrum antibiotics, especially fluoroquinolones and amoxicillin with clavulanic acid, are still high in Belgium.Conclusion: Almost two decades of multi-faceted campaigning coincide with improvements in antibiotic awareness among the public and prescribers, outpatient antibiotic use and resistance. Nevertheless, additional efforts are needed to reach the targets set in BAPCOC's national action plan 2014-2019. Therefore, a new national action plan was developed for 2020-2024 using a One Health approach.

Lower respiratory tract infection in the community: associations between viral aetiology and illness course.

OBJECTIVES: This study determined associations between respiratory viruses and subsequent illness course in primary care adult patients presenting with acute cough and/or suspected lower respiratory tract infection. METHODS: A prospective European primary care study recruited adults with symptoms of lower respiratory tract infection between November 2007 and April 2010. Real-time in-house polymerase chain reaction (PCR) was performed to test for six common respiratory viruses. In this secondary analysis, symptom severity (scored 1 = no problem, 2 = mild, 3 = moderate, 4 = severe) and symptom duration were compared between groups with different viral aetiologies using regression and Cox proportional hazard models, respectively. Additionally, associations between baseline viral load (cycle threshold (Ct) value) and illness course were assessed. RESULTS: The PCR tested positive for a common respiratory virus in 1354 of the 2957 (45.8%) included patients. The overall mean symptom score at presentation was 2.09 (95% confidence interval (CI) 2.07-2.11) and the median duration until resolution of moderately bad or severe symptoms was 8.70 days (interquartile range 4.50-11.00). Patients with influenza virus, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), coronavirus (CoV) or rhinovirus had a significantly higher symptom score than patients with no virus isolated (0.07-0.25 points or 2.3-8.3% higher symptom score). Time to symptom resolution was longer in RSV infections (adjusted hazard ratio (AHR) 0.80, 95% CI 0.65-0.96) and hMPV infections (AHR 0.77, 95% CI 0.62-0.94) than in infections with no virus isolated. Overall, baseline viral load was associated with symptom severity (difference 0.11, 95% CI 0.06-0.16 per 10 cycles decrease in Ct value), but not with symptom duration. CONCLUSIONS: In healthy, working adults from the general community presenting at the general practitioner with acute cough and/or suspected lower respiratory tract infection other than influenza impose an illness burden comparable to influenza. Hence, the public health focus for viral respiratory tract infections should be broadened.

Point Prevalence Survey of Antimicrobial Prescribing in a Nigerian Hospital: Findings and Implications on Antimicrobial Resistance.

BACKGROUND: Antimicrobial resistance is a global health challenge. There is inadequate information on antimicrobial prescribing practices in many sub-Saharan African countries including Nigeria. A standardized method for surveillance of antimicrobial use in hospitals was employed to assess the antimicrobial prescribing practices in UCH, Ibadan, Nigeria. METHODS: A point prevalence survey (PPS) was conducted in December 15, 2017 at the UCH Ibadan. The survey included all in-patients receiving an antimicrobial on the day of PPS. Data collected included details on the antimicrobial agents, reasons and indications for treatment as well as a set of quality indicators. A web-based application was used for data-entry, validation and reporting as designed by the University of Antwerp (www.global-pps.be). RESULTS: This survey included 451 patients from 38 different wards of which 59.6% received at least one antimicrobial. The neonatal medical wards contributed the highest number of patients who received antibiotics. A total of 172 therapeutic antibiotic prescriptions were issued, mainly for Community Acquired Infections (n=119; 69.2%). Most prescriptions for Healthcare Associated Infections (n=53) were intervention related (47.2%). Frequently used antibiotics include third generation cephalosporins (23.9%; mainly ceftriaxone); followed by combination of penicillin's (17.4%; mainly amoxicillin with enzyme inhibitor) and fluoroquinolones (16.6%). Majority, 312(69.9%)of the patients had parenteral antibiotics and only 95 (21.3%) of all antibiotic prescriptions had a documented stop or review date. Although the reason for antibiotic prescription was indicated for 413 (92.4%) prescriptions, targeted therapy was the basis for only 17 (3.8%)of these prescriptions. For surgical prophylaxis, 98.7% of all prescriptions were given for more than one day. Compliance to guidelines was non-existent. CONCLUSION: Our findings showed high broad spectrum prescribing, high number of intervention related health care infections, high use of prolonged surgical prophylaxis, inexistence of local guidelines; and low utilization of laboratory facilities. Hospital related intervention should include development of antibiotic guideline and increased enlightenment on rational prescribing practices.

A comparative study between real-time PCR and loop-mediated isothermal amplification to detect carbapenemase and/or ESBL genes in Enterobacteriaceae directly from bronchoalveolar lavage fluid samples.

OBJECTIVES: To evaluate and compare the efficacy of real-time PCR (Xpert Carba-R) and loop-mediated isothermal amplification (Eazyplex® SuperBug CRE) for detecting carbapenemase carriage in Enterobacteriaceae directly from bronchoalveolar lavage (BAL). METHODS: Negative BAL samples were spiked with 21 well-characterized carbapenemase-producing Enterobacteriaceae strains to a final concentration of 102-104 cfu/mL. Xpert Carba-R (Cepheid, Sunnyvale, CA, USA), which detects five targets (blaKPC, blaNDM, blaVIM, blaOXA-48 and blaIMP-1), and the Eazyplex® SuperBug CRE system (Amplex-Diagnostics GmbH, Germany), which detects seven genes (blaKPC, blaNDM, blaVIM, blaOXA-48, blaOXA-181, blaCTXM-1 and blaCTXM-9), were evaluated for the detection of these genes directly from BAL samples. RESULTS: Xpert Carba-R showed 100% agreement with carbapenemase characterization by PCR and sequencing for all final bacteria concentrations. Eazyplex® SuperBug CRE showed 100%, 80% and 27% agreement with PCR and sequencing when testing 104, 103 and 102 cfu/mL, respectively. False negative results for Eazyplex® SuperBug CRE matched the highest cycle threshold values for Xpert Carba-R. Hands-on time for both assays was about 15 min, but Eazyplex® SuperBug CRE results were available within 30 min, whereas Xpert Carba-R took around 50 min. CONCLUSIONS: We here describe the successful use of two commercial diagnostic tests, Xpert Carba-R and Eazyplex® SuperBug CRE, to detect bacterial carbapenem resistance genes directly in lower respiratory tract samples. Our results could be used as proof-of-concept data for validation of these tests for this indication.

Antibiotic use among surgical inpatients at a tertiary health facility: a case for a standardized protocol for presumptive antimicrobial therapy in the developing world.

BACKGROUND: Indiscriminate antimicrobial use is one of the greatest contributors to antimicrobial resistance. A low level of asepsis in hospitals and inadequate laboratory support have been adduced as reasons for indiscriminate use of antimicrobials among surgical patients. At present, there are no guidelines for presumptive antibiotic use in Nigeria and sub-Saharan Africa. AIM: Surgical inpatients at the study hospital were surveyed to determine the level of antimicrobial use and degree of compliance with prescription quality indicators. METHODS: A cross-sectional survey was conducted among all surgical inpatients in May 2019 using a standardized tool developed by the University of Antwerp to assess the point prevalence of antimicrobials. Inpatients who were admitted from 08:00 h on the day of the survey were included. Data on patients' demographics, indication for antimicrobial use, reason for antimicrobial use, stop/review date, adherence to guidelines and laboratory use were collected. The prevalence of antimicrobial use in the surgical department was estimated. RESULTS: Eighty-two inpatients were included in the survey. Of these, 97.6% were receiving at least one antimicrobial agent. Only 5.4% of the prescriptions were targeted, and 37.6% of prescriptions were for empirical treatment of infections. Approximately half (50.7%) of the patients were receiving presumptive antibiotics, and 6% were receiving prophylactic antibiotics. In total, 58.7% of prescriptions were administered parenterally, and 98.2% of patients had documentation of a stop/review date. Metronidazole (P=32.3%, T=29.2%), ceftriaxone (P=28.4%, T=19.8%) and ciprofloxacin (P=14.2%, T=14.6%) were the most common antimicrobials used. CONCLUSIONS: There is a high rate of antimicrobial use among surgical inpatients, and the rate of indiscriminate antimicrobial prescribing among these patients needs to be reduced. This can be achieved by developing antimicrobial guidelines for presumptive antimicrobial therapy.

Global point prevalence survey of antimicrobial consumption in Brazilian hospitals.

BACKGROUND: The inappropriate use of antimicrobials and increased rates of antimicrobial resistance is a challenge all over the world. Although antibiotic stewardship is recommended by the Brazilian government, data regarding antibiotic use in Brazilian hospitals are scarce. The aim of this study was to conduct a point prevalence survey of antimicrobial use in 18 Brazilian hospitals. METHODS: Eighteen Brazilian hospitals conducted the Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS) in 2017. The study enrolled inpatients on antimicrobials. Data collection included details on the antimicrobial prescriptions. A web-based programme was used for data-entry, validation and reporting. The Global-PPS was developed by the University of Antwerp and bioMérieux provided funding support. FINDINGS: A total of 1801 patients were evaluated, of which 941 (52.2%) were on antimicrobials. Four hundred (42.5%) patients were given at least two antimicrobials. Out of the 1317 antibacterials for systemic use, 514 (39%) were prescribed for community-acquired infections, 533 (40.5%) for healthcare-associated infections and 248 (18.8%) for prophylactic use. The most frequently used antimicrobials were ceftriaxone (12.8%), meropenem (12.3%) and vancomycin (10.3%). Pneumonia or lower respiratory tract infection was the most common site of infection (29.2%). In general, antimicrobials were given mainly parenterally (91%) and empirically (81.2%). CONCLUSIONS: A high prevalence of antibiotic use was observed in the 18 Brazilian hospitals. The antibiotics were prescribed mainly empirically. Intravenous broad-spectrum antibiotics were the most frequent antimicrobials used, showing that reinforcement of de-escalation strategy is needed. The Global-PPS data can be very useful for monitoring stewardship programmes and intervention.

THE GLOBAL POINT PREVALENCE SURVEY (PPS) OF ANTIMICROBIAL USE AND ANTIMICROBIAL RESISTANCE AMONG HOSPITALIZED CHILDREN IN GEORGIA.

The aims of our study were to determine antibiotic prescribing rates for prevention and treatment of infections in pediatric units, to evaluate the number and type of antimicrobial agents and administration route, reveal commonly used antibiotic subgroups and identify targets for improving the quality of antimicrobial prescribing. A 1-day PPS (Point Prevalence Study) on antibiotic use in hospitalized children was performed in Georgia from 2015 to 2019. 18 clinics in different regions of Georgia were included in the survey. Antimicrobial prevalence rates increased over the years from 60.1% in 2015 to 92.6% in 2018. The most commonly, antibiotics were prescribed for lower respiratory tract infections (LRTI). In 2015 25.1% of LRTI were treated by ampicillin-sulbactam but the next year it replaced with ceftriaxone (37.1% in 2017 and 38.2% in 2018). In pediatric surgical ward, the antibiotics were commonly prescribed for surgical prevention (54.1% in 2015, 32.3% in 2018). The most common conditions treated with antibiotics in neonates were sepsis (30.1%) and LRTI (45.3%). The most used antibiotic was ceftriaxone (33.3% in 2015). Ampicilin-sulbactam was prescribed in 28.1% of pneumonia case in neonates in 2018. In 2015 antibiotics were mainly prescribed empirically (98.0%). In 2018 resistance of MRSA was 8.1%, and resistance to the third-generation cephalosporin 17.3%. Prevalence rate of antibiotics for prevention and treatment of infection disease in pediatric units increased in 2018. Main feasible targets for optimization of antibiotic prescribing have been identified: high use of broad-spectrum antibiotics in hospitals, high frequency of empirical treatment, rarely performed culture tests, prolonged antibiotic prophylaxis in surgery patients and an alarming raise of resistant strains. The implementation of disease-specific clinical pathways associated with annual PPSs could be a good way to monitor and improve antibiotic prescription patterns in neonatal and pediatric inpatients over time.

Variations in antibiotic use across India: multi-centre study through Global Point Prevalence survey.

The aim of the study was to assess antimicrobial prescribing patterns, and variation in practice, in India. A point prevalence survey (PPS) was conducted in October to December 2017 in 16 tertiary care hospitals across India. The survey included all inpatients receiving an antimicrobial on the day of PPS and collected data were analysed using a web-based application of the University of Antwerp. In all, 1750 patients were surveyed, of whom 1005 were receiving a total of 1578 antimicrobials. Among the antimicrobials prescribed, 26.87% were for community-acquired infections; 19.20% for hospital-acquired infections; 17.24% for medical prophylaxis; 28.70% for surgical prophylaxis; and 7.99% for other or undetermined reasons. Antibiotic prescribing quality indicators, such as reason in notes and post-prescription review score, were low. This PPS showed widespread antibiotic usage, underlining the need for antibiotic stewardship to promote evidence-based practice.

Remarkable geographical variations between India and Europe in carriage of the staphylococcal surface protein-encoding sasX/sesI and in the population structure of methicillin-resistant Staphylococcus aureus belonging to clonal complex 8.

OBJECTIVES: sasX is a colonization-virulence factor that potentially underlies the success of methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 239 in Asia. We aimed to study the spread of sasX and the population structure of MRSA in two geographically distinct regions, Europe and India. METHODS: MRSA (n = 128) from screening and clinical samples from tertiary care patients in 12 European countries (n = 119), and from India (n = 9) were multilocus-sequence-typed and screened for sasX and its carrier φSPß-like prophage by PCR. Whole genome sequencing was performed on sasX-harbouring strains from India (n = 5) and Europe (n = 2) and on a selection non-harbouring sasX (n = 36) (2 × 150 bp, Miseq, Illumina). Reads were mapped to the ST239 reference strain, TW20. RESULTS: sasX and sesI, a sasX homologue native to Staphylococcus epidermidis, were detected in five of the nine Indian MRSA belonging to ST239 and to other sequence types of CC8. In contrast, sasX was restricted to two ST239 strains in Europe. The intact sasX and sesI carrier φSPß-like prophages were ∼80 kb and ∼118 kb, and integrated in the yeeE gene. We identified 'novel' ST239 clades in India and Serbia that showed significant differences in base substitution frequencies (0.130 and 0.007, respectively, Tamura-Nei model) (p <0.05). CONCLUSIONS: Our data highlight dissemination of sasX to non-ST239 sequence types of CC8. Detection of the S. epidermidis-associated sesI in MRSA provided unquestionable evidence of transfer between the two species. Stark differences in evolutionary rates between the novel Indian and Serbian ST239 clades identified here might be due to inherent clade characteristics or influenced by other environmental differences such as antibiotic use.

Detection and prevalence of carbapenem-resistant Gram-negative bacteria among European laboratories in the COMBACTE network: a COMBACTE LAB-Net survey.

Antimicrobial resistance (AMR) represents a global public health threat that jeopardises the progress medicine has made over the last century. To confront AMR, the Innovative Medicines Initiative (IMI) has supported the development of a large network of hospitals and laboratories in Europe as part of the New Drugs for Bad Bugs (ND4BB) programme and the COMBACTE projects. COMBACTE LAB-Net conducted a pilot survey on distribution and usage of carbapenem resistance detection methods among laboratories in the COMBACTE network in two clinical trials as part of the COMBACTE-CARE project. The survey was sent out to 211 laboratories in 20 European countries between May 2015 and June 2017. Answers were collected from 165 laboratories (78%). Sixty laboratories (36%) reported an outbreak of carbapenem-resistant (CR) Enterobacteriaceae during one of the two years preceding the completion of the survey. High rates of CR Acinetobacter spp. above 50% were reported by 74 laboratories (47%), particularly in the Western Balkan countries where the rates were sometimes higher than 90%. Apart from determining the antimicrobial susceptibility of isolates, laboratories also used various methods, such as Matrix Assisted Laser Desorption Ionization - Time of Flight (MALDI-TOF), Carbapenemase Nordmann-Poirel (Carba NP) test or molecular methods, to detect CR Gram-negative bacteria. The survey resulted in the selection of sites with high resistance rates that successfully recruited many patients in the EURECA observational clinical trial.

Author Correction: Multidisciplinary study of the secondary immune response in grandparents re-exposed to chickenpox.

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Longitudinal point prevalence survey of antibacterial use in Northern Ireland using the European Surveillance of Antimicrobial Consumption (ESAC) PPS and Global-PPS tool.

Antimicrobial resistance is a limiting factor for the success of the treatment of infectious diseases and is associated with increased morbidity and cost. The present study aims to evaluate prescribing patterns of antimicrobials and quantify progress in relation to targets for quality improvement in the prescription of antimicrobials in Northern Ireland's secondary care sector using three repetitive point prevalence surveys (PPS) over a 6-year period: the European Surveillance of Antimicrobial Consumption (ESAC-PPS) in 2009 and 2011 and the Global-PPS on Antimicrobial Consumption and Resistance in 2015. Out of 3605 patients surveyed over the three time points, 1239 (34.4%) were treated with an antibiotic, the most frequently prescribed antibiotic groups were a combination of penicillins, including ß-lactamase inhibitors. Compliance with hospital antibiotic policies in 2009, 2011 and 2015 were 54.5%, 71.5% and 79.9%, respectively. Likewise, an indication for treatment was recorded in patient notes 88.5%, 87.7% and 90.6% in 2009, 2011 and 2015, respectively, and surgical prophylactic antibiotic prescriptions for >24 h was 3.9%, 3.2% and 0.7% in 2009, 2011 and 2015, respectively. Treatment based on biomarker data was used in 61.5% of cases. In conclusion, a general trend in the improvement of key antimicrobial-related quality indicators was noted. The PPS tool provided a convenient, inexpensive surveillance system of antimicrobial consumption and should be considered an essential component to establish and maintain informed antibiotic stewardship in hospitals.

Aetiology of lower respiratory tract infection in adults in primary care: a prospective study in 11 European countries.

OBJECTIVES: To describe the role of bacteria (including bacterial resistance), viruses (including those recently described) and mixed bacterial-viral infections in adults presenting to primary care with lower respiratory tract infection (LRTI). METHODS: In all, 3104 adults with LRTI were enrolled, of whom 141 (4.5%) had community-acquired pneumonia (CAP), and 2985 matched controls in a prospective study in 16 primary care networks in Europe, and followed patients up at 28-35 days. We detected Streptococcus pneumoniae and Haemophilus influenzae and assessed susceptibility, atypical bacteria and viruses. RESULTS: A potential pathogen was detected in 1844 (59%) (in 350 (11%) bacterial pathogens only, in 1190 (38%) viral pathogens only, and in 304 (10%) both bacterial and viral pathogens). The most common bacterial pathogens isolated were S. pneumoniae (5.5% overall, 9.2% in CAP patients) and H. influenzae (5.4% overall, 14.2% in CAP patients). Less than 1% of S. pneumoniae were highly resistant to penicillin and 12.6% of H. influenzae were ß-lactamase positive. The most common viral pathogens detected were human rhinovirus (20.1%), influenza viruses (9.9%), and human coronavirus (7.4%). Influenza virus, human parainfluenza viruses and human respiratory syncytial virus as well as human rhinovirus, human coronavirus and human metapneumovirus were detected significantly more frequently in LRTI patients than in controls. CONCLUSIONS: A bacterial pathogen is identified in approximately one in five adult patients with LRTI in primary care, and a viral pathogen in just under half, with mixed infections in one in ten. Penicillin-resistant pneumococci and ß-lactamase-producing H. influenzae are uncommon. These new findings support a restrictive approach to antibiotic prescribing for LRTI and the use of first-line, narrow-spectrum agents in primary care.

Effect of outpatient antibiotics for urinary tract infections on antimicrobial resistance among commensal Enterobacteriaceae: a multinational prospective cohort study.

OBJECTIVES: We quantified the impact of antibiotics prescribed in primary care for urinary tract infections (UTIs) on intestinal colonization by ciprofloxacin-resistant (CIP-RE) and extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE), while accounting for household clustering. METHODS: Prospective cohort study from January 2011 to August 2013 at primary care sites in Belgium, Poland and Switzerland. We recruited outpatients requiring antibiotics for suspected UTIs or asymptomatic bacteriuria (exposed patients), outpatients not requiring antibiotics (non-exposed patients), and one to three household contacts for each patient. Faecal samples were tested for CIP-RE, ESBL-PE, nitrofurantoin-resistant Enterobacteriaceae (NIT-RE) and any Enterobacteriaceae at baseline (S1), end of antibiotics (S2) and 28 days after S2 (S3). RESULTS: We included 300 households (205 exposed, 95 non-exposed) with 716 participants. Most exposed patients received nitrofurans (86; 42%) or fluoroquinolones (76; 37%). CIP-RE were identified in 16% (328/2033) of samples from 202 (28%) participants. Fluoroquinolone treatment caused transient suppression of Enterobacteriaceae (S2) and subsequent two-fold increase in CIP-RE prevalence at S3 (adjusted prevalence ratio (aPR) 2.0, 95% CI 1.2-3.4), with corresponding number-needed-to-harm of 12. Nitrofurans had no impact on CIP-RE (aPR 1.0, 95% CI 0.5-1.8) or NIT-RE. ESBL-PE were identified in 5% (107/2058) of samples from 71 (10%) participants, with colonization not associated with antibiotic exposure. Household exposure to CIP-RE or ESBL-PE was associated with increased individual risk of colonization: aPR 1.8 (95% CI 1.3-2.5) and 3.4 (95% CI 1.3-9.0), respectively. CONCLUSIONS: These findings support avoidance of fluoroquinolones for first-line UTI therapy in primary care, and suggest potential for interventions that interrupt household circulation of resistant Enterobacteriaceae.

Amoxicillin for acute lower respiratory tract infection in primary care: subgroup analysis by bacterial and viral aetiology.

OBJECTIVE: We aimed to assess the effects of amoxicillin treatment in adult patients presenting to primary care with a lower respiratory tract infection (LRTI) who were infected with a potential bacterial, viral, or mixed bacterial/viral infection. METHODS: This multicentre randomized controlled trial focused on adults with LRTI not suspected for pneumonia. Patients were randomized to receive either antibiotic (amoxicillin 1 g) or placebo three times daily for 7 consecutive days using computer-generated random numbers (follow-up 28 days). In this secondary analysis of the trial, symptom duration (primary outcome), symptom severity (scored 0-6), and illness deterioration (reconsultation with new or worsening symptoms, or hospital admission) were analysed in pre-specified subgroups using regression models. Subgroups of interest were patients with a (strictly) bacterial, (strictly) viral, or combined infection, and patients with elevated values of procalcitonin, C-reactive protein, or blood urea nitrogen. RESULTS: 2058 patients (amoxicillin n = 1036; placebo n = 1022) were randomized. Treatment did not affect symptom duration (n = 1793). Patients from whom a bacterial pathogen only was isolated (n = 207) benefited from amoxicillin in that symptom severity (n = 804) was reduced by 0.26 points (95% CI -0.48 to -0.03). The odds of illness deterioration (n = 2024) was 0.24 (95% CI 0.11 to 0.53) times lower from treatment with amoxicillin when both a bacterial and a viral pathogen were isolated (combined infection; n = 198). CONCLUSIONS: Amoxicillin may reduce the risk of illness deterioration in patients with a combined bacterial and viral infection. We found no clinically meaningful benefit from amoxicillin treatment in other subgroups.