Community Antibiotic Use at the Population Level During the SARS-CoV-2 Pandemic in British Columbia, Canada.

BACKGROUND: The objective of this study was to examine the aggregate rates of antibiotic use at the population level and compare these rates over time against historical averages to identify the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting control measures on community prescribing. METHODS: We collected antibiotic prescriptions and physician office visits from January 1, 2016, to July 21, 2020. We calculated monthly prescription rates stratified by sex, age group, profession, diagnosis type, and antibiotic class. We looked at monthly prescription rate as a moving average over time. Using the interrupted time series analysis method, we estimated the changes in prescription rates after March 2020. RESULTS: The moving average of overall monthly prescription rates during January-June 2020 was below the minimum of the historical years' moving averages (2016-2019). We observed a >30% reduction in overall monthly prescription rates in April, May, and July of 2020 compared with the same months of 2019. We observed that overall monthly prescription rates experienced a significant level change of -12.79 (P < .001) during the coronavirus disease 2019 pandemic after March 2020, with the greatest level change being -18.02 among children 1-4 years of age (P < .001). We estimated an average -5.94 (P < .001) change in respiratory tract infection (RTI)-associated monthly prescription rates after March 2020. Overall prescription rates comparing January-July 2019 and their 2020 counterparts showed a decrease in monthly prescribing ranging from -1 to -5 for amoxicillin, amoxicillin and enzyme inhibitors, azithromycin, clarithromycin, and sulfamethoxazole. CONCLUSIONS: In British Columbia, Canada, overall and RTI-specific monthly antibiotic prescription rates declined significantly during April-July 2020 compared with the same months in prepandemic years.

Cost-benefit analysis of a population-based education program on the wise use of antibiotics.

OBJECTIVE: In 2005, the Do Bugs Need Drugs (DBND) program was imported to British Columbia (BC) from Alberta with the goal of reducing unnecessary antibiotic use in the community. The objective of this study was to estimate the impact of the program on antibiotic-associated costs and cost-benefit. METHODS: We used data on antibiotic prescription and costs from BC PharmaNet for the period of 1996 to 2014. We conducted interrupted time series regression to formally interpret the impact of the DBND program. RESULTS: The average monthly prescription rate fell by 14.5%, from 54.3 to 46.4 per 1000 population between 2005 and 2014. The proportionate contribution of macrolide prescription decreased from 19.2% in 2005 to 13.2% in 2014 and for quinolones decreased from 13.1% in 2005 to 12% in 2014. The proportion of prescriptions for both penicillins and tetracyclines increased by > 35.5%. Before the program, the average monthly cost of antibiotics was increasing by CAD $8.12 per 1000 population (p < 0.001). After program introduction, average monthly cost decreased by CAD $18.19 per 1000 population (p < 0.001), creating an annual savings for BC in 2014 of CAD $83.6 million. In 2014, one Canadian dollar spent on the DBND program was associated with conservative savings of CAD $76.20. CONCLUSION: Significant cost savings have been observed in association with a community antimicrobial stewardship program focused on both public and prescribers. Such programs are an effective strategy in cost-benefit terms and should therefore be considered for universal adoption in Canadian healthcare systems.

Susceptibility of clinical Moraxella catarrhalis isolates in British Columbia to six empirically prescribed antibiotic agents.

BACKGROUND: Moraxella catarrhalis is a commensal organism of the respiratory tract that has emerged as an important pathogen for a variety of upper and lower respiratory tract infections including otitis media and acute exacerbations of chronic bronchitis. Susceptibility testing of M catarrhalis is not routinely performed in most diagnostic laboratories; rather, a comment predicting susceptibility based on the literature is attached to the report. The most recent Canadian report on M catarrhalis antimicrobial susceptibility was published in 2003; therefore, a new study at this time was of interest and importance. OBJECTIVE: To determine the susceptibility of M catarrhalis isolates from British Columbia to amoxicillin-clavulanate, doxycycline, clarithromycin, cefuroxime, levofloxacin and trimethoprimsulfamethoxazole. METHODS: A total of 117 clinical M catarrhalis isolates were isolated and tested from five Interior hospitals and two private laboratory centres in British Columbia between January and December 2012. Antibiotic susceptibility of M catarrhalis isolates was characterized using the Etest (E-strip; bioMérieux, USA) according to Clinical Laboratory Standards Institute guidelines. RESULTS: All isolates were sensitive to amoxicillin-clavulanate, doxycycline, clarithromycin, levofloxacin and trimethoprimsulfamethoxazole. One isolate was intermediately resistant to cefuroxime, representing a 99.15% sensitivity rate to the cephem agent. Cefuroxime minimum inhibitory concentrations (MICs) inhibiting 50% and 90% of organisms (MIC50 and MIC90) were highest among the antibiotics tested, and the MIC90 (3 µg/mL) of cefuroxime reached the Clinical Laboratory Standards Institute breakpoint of susceptibility. DISCUSSION: The antibiotic susceptibility of M catarrhalis isolates evaluated in the present study largely confirms the findings of previous surveillance studies performed in Canada. Cefuroxime MICs are in the high end of the sensitive range and the MIC50 and MIC90 observed in the present study are the highest ever reported in Canada. CONCLUSION: Although cefuroxime MICs in M catarrhalis are high, all agents tested showed antimicrobial activity, supporting their continued therapeutic and empirical use.

HISTORIQUE: Le Moraxella catarrhalis est un organisme commensal des voies respiratoires, qui se révèle un pathogène important dans diverses infections des voies respiratoires supérieures et inférieures, y compris l'otite moyenne et les exacerbations aiguës de la bronchite chronique. Dans la plupart des laboratoires diagnostiques, les tests de susceptibilité au M catarrhalis ne sont pas effectués systématiquement. Un commentaire en prédisant la susceptibilité d'après les publications est joint au rapport. Le dernier rapport canadien sur la susceptibilité du M catarrhalis aux antimicrobiens a été publié en 2003. Il est donc judicieux et important de publier une nouvelle étude à ce sujet. OBJECTIF: Déterminer la susceptibilité des isolats de M catarrhalis provenant de la Colombie-Britannique à l'amoxicilline-clavulanate, à la doxycycline, à la clarithromycine, à la céfuroxime, à la lévofloxacine et au triméthoprime-sulfaméthoxazole. MÉTHODOLOGIE: Au total, 117 isolats cliniques de M catarrhalis provenant de cinq hôpitaux de l'intérieur et de deux laboratoires privés de la Colombie-Britannique ont été prélevés et examinés entre janvier et décembre 2012. Les chercheurs ont caractérisé la susceptibilité aux antibiotiques des isolats de M catarrhalis au moyen de l'Etest (E-strip; bioMérieux, États-Unis), conformément aux lignes directrices du Clinical Laboratory Standards Institute. RÉSULTATS: Tous les isolats étaient sensibles à l'amoxicillineclavulanate, à la doxycycline, à la clarithromycine, à la lévofloxacine et au triméthoprime-sulfaméthoxazole. Un isolat était moyennement résistant à la céfuroxime, représentant un taux de sensibilité de 99,15 % à l'agent céphème. Les concentrations minimales inhibitrices (CMI) de la céfuroxime inhibant 50 % et 90 % des organismes (CMI50 et CMI90) étaient les plus élevées des antibiotiques à l'étude, et la CMI90 (3 µg/mL) de la céfuroxime atteignait le seuil de susceptibilité du Clinical Laboratory Standards Institute. EXPOSÉ: La susceptibilité des isolats de M catarrhalis aux antibiotiques évalués dans la présente étude confirme largement les observations tirées d'études de surveillance antérieures effectuées au Canada. Les CMI de la céfuroxime se situent dans la plage supérieure de sensibilité. De plus, la CMI50 et la CMI90 observées dans la présente étude sont les plus élevées jamais déclarées au Canada. CONCLUSION: Même si les CMI de la céfuroxime dans les isolats de M catarrhalis sont élevées, tous les agents étudiés présentaient une activité antimicrobienne, ce qui appuie la poursuite de leur utilisation dans un cadre thérapeutique et empirique.

Determination of susceptibility to fosfomycin and tigecycline of Enterobacteriaceae, particularly Escherichia coli isolates, producing extended-spectrum ß-lactamases from multiple regional Canadian hospitals.

BACKGROUND: The worldwide spread of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae, particularly Escherichia coli, has significantly limited therapeutic options, especially for urinary tract infections. Although limited in their indications, fosfomycin and tigecycline are potential agents to treat infections due to ESBL-producing organisms. Although not routinely performed, susceptibility testing to both is necessary to ensure there is not an increase in resistance. METHODS: A total of 160 isolates of ESBL-producing E coli were isolated from patients at multiple regional hospitals in the Interior Health Region of British Columbia from June 2009 to January 2012. Isolates were obtained from various body fluids and sites including urine (78.2%), wounds, blood, gall bladder drain and respiratory specimens. All isolates were tested using the E-test method (Etest, bioMérieux, France) for tigecycline and Kirby Bauer disk diffusion method for fosfomycin using European Committee of Antimicrobial Susceptibility Testing breakpoints for tigecycline and Clinical and Laboratory Standards Institute zone sizes for fosfomycin. RESULTS: All 160 isolates were found to be susceptible to tigecycline, while five isolates (3.1%) were resistant to fosfomycin (four resistant, one intermediate). CONCLUSION: Although resistance to these antibiotics has previously been reported, the present study confirmed that isolates of ESBL-producing E coli from the Interior Health Region of British Columbia remain highly susceptible to both tigecycline and fosfomycin.

HISTORIQUE: La propagation mondiale des entérobactériacées produisant des ß-lactamases à large spectre (BLLS), notamment l'Escherichia coli, se heurte à un nombre d'options thérapeutiques très limité, particulièrement en cas d'infections urinaires. Même si leurs indications sont limitées, la fosfomycine et la tigécycline sont des agents potentiels pour traiter les infections causées par des organismes produisant des BLLS. Les tests de susceptibilité ne sont pas effectués systématiquement, mais ils sont nécessaires pour s'assurer que la résistance à ces deux agents n'augmente pas. MÉTHODOLOGIE: Au total, 160 isolats d'E coli produisant des BLLS ont été isolés chez des patients provenant de multiples hôpitaux régionaux de la régie régionale de la santé Interior de la Colombie-Britannique entre juin 2009 et janvier 2012. Ces isolats provenaient de divers foyers de liquides corporels, y compris l'urine (78,2 %), les plaies, le sang, le drain de la vésicule biliaire et des spécimens respiratoires. Les chercheurs ont testé tous les isolats au moyen de la méthode E-test (Etest, bioMérieux, France) pour la tigécycline, selon le point de cassure du Comité européen des antibiogrammes, et au moyen de la méthode par diffusion des disques imprégnés de Kirby Bauer pour la fosfomycine, selon les dimensions de la zone du Clinical and Laboratory Standards Institute. RÉSULTATS: Les 160 isolats étaient susceptibles à la tigécycline, tandis que cinq isolats (3,1 %) étaient résistants à la fosfomycine (quatre résistants, un intermédiaire). CONCLUSION: Même si des cas de résistance à ces antibiotiques ont déjà été déclarés, la présente étude confirme que les isolats d'E coli produisant des BLLS provenant de la régie régionale de la santé Interior de la Colombie-Britannique demeurent hautement susceptibles à la fois à la tigécycline et à la fosfomycine.

Penicillin susceptibility and macrolide-lincosamide-streptogramin B resistance in group B Streptococcus isolates from a Canadian hospital.

BACKGROUND: Intrapartum antibiotic prophylaxis (IAP) is recommended for pregnant women who test positive for group B Streptococcus (GBS) in their genitourinary tract to prevent GBS-induced neonatal sepsis. Penicillin G is used as the primary antibiotic, and clindamycin or erythromycin as the secondary, if allergies exist. Decreased susceptibility to penicillin G has occasionally been reported; however, clindamycin and erythromycin resistance is on the rise and is causing concern over the use of clindamycin and erythromycin IAP. METHODS: Antibiotic resistance was characterized phenotypically using a D-Test for erythromycin and clindamycin, while an E-Test (E-strip) was used for penicillin G. GBS was isolated from vaginal-rectal swabs and serologically confirmed using Prolex (Pro-Lab Diagnostics, Canada) streptococcal grouping reagents. Susceptibility testing of isolates was performed according to the Clinical Laboratory Standards Institute guidelines. RESULTS: All 158 isolates were penicillin G sensitive. Inducible macrolide-lincosamide-streptogramin B (MLSB) resistance was observed in 13.9% of isolates. Constitutive MLSB resistance was observed in 12.7% of isolates. M phenotype resistance was observed in 6.3% of isolates. In total, erythromycin resistance was present in 32.9% of the GBS isolates, while clindamycin resistance was present in 26.6%. DISCUSSION: The sampled GBS population showed no sign of reduced penicillin susceptibility, with all being well under susceptible minimum inhibitory concentration values. These data are congruent with the large body of evidence showing that penicillin G remains the most reliable clinical antibiotic for IAP. Clindamycin and erythromycin resistance was higher than expected, contributing to a growing body of evidence that suggests the re-evaluation of clindamycin and erythromycin IAP is warranted.

HISTORIQUE: La prophylaxie antibiotique intrapartum (PAI) est recommandée chez les femmes enceintes positives au Streptococcus du groupe B (SGB) dans l'appareil génito-urinaire, afin de prévenir la septicémie néonatale induite par le SGB. La pénicilline G est utilisée comme antibiotique primaire et, en cas d'allergies, la clindamycine ou l'érythromycine comme antibiotique secondaire. On déclare parfois une diminution de la susceptibilité à la pénicilline G, mais la résistance à la clindamycine et à l'érythromycine est à la hausse et suscite des inquiétudes quant à leur utilisation en PAI. MÉTHODOLOGIE: Les chercheurs ont caractérisé les phénotypes de résistance aux antibiotiques au moyen d'un test de diffusion pour l'érythromycine et la clindamycine et d'un test E (bandelette E) pour la pénicilline G. Ils ont isolé le SGB dans les écouvillons vagino-rectaux et en ont fait la confirmation sérologique au moyen des réactifs de groupement streptococcique Prolex (Pro-Lab Diagnostics, Canada). Les tests de susceptibilité des isolats ont été exécutés conformément aux lignes directrices du Clinical Laboratory Standards Institute. RÉSULTATS: Les 158 isolats étaient sensibles à la pénicilline G. Les chercheurs ont observé une résistance au macrolide, à la lincosamide et à la streptogramine de type B (MLSB) dans 13,9 % des isolats. Ils ont observé une résistance à MLSB dans 12,7 % des isolats et la résistance au phénotype M dans 6,3 % des isolats. Au total, ils ont constaté une résistance à l'érythromycine dans 32,9 % des isolats de SGB, et une résistance à la clindamycine dans 26,6 % des cas. EXPOSÉ: L'échantillon de population atteint du SGB n'a révélé aucun signe de diminution de la susceptibilité à la pénicilline, car tous les sujets se situaient bien en deçà des valeurs CMI susceptibles. Ces données coïncident avec le vaste ensemble de données probantes démontrant que la pénicilline G demeure l'antibiotique clinique le plus fiable pour la PIA. La résistance à la clindamycine et à l'érythromycine était plus élevée que prévu, ce qui contribue à l'ensemble croissant de données probantes indiquant qu'il faut réévaluer la PIA à la clindamycine et à l'érythromycine.

Evaluation of the Do Bugs Need Drugs? program in British Columbia: Can we curb antibiotic prescribing?

OBJECTIVE: Antibiotic resistance is accelerated by the overuse of antibiotics. Do Bugs Need Drugs? is an educational program adapted in British Columbia to target both the public and health care professionals, with the aim of reducing unnecessary prescribing. The current article presents a descriptive evaluation of the impact of the program over the first four years. METHOD: Program implementation was measured by the amount of educational material distributed and the level of participation in educational sessions. The impact of the program was assessed by measuring changes in knowledge and prescribing habits of participating physicians, and by investigating provincial trends in antibiotic use. RESULTS: A total of 51,367 children, assisted-living residents and health care professionals have participated in the program since its inception in the fall of 2005. Pre- and postcourse assessments of participating physicians indicated significant improvements in clinical knowledge and appropriate antibiotic treatment of upper respiratory tract infections. Overall rates of antibiotic use in the province have stabilized since 2006. The rates of consumption of fluoroquinolones and macrolides have levelled off since 2005. Utilization rates for acute bronchitis are at the same level as when the program was first implemented, but rates for other acute upper respiratory tract infections of interest have declined. CONCLUSIONS: The Do Bugs Need Drugs? program significantly improves physician antibiotic prescription decisions and is ecologically associated with desirable change in population antibiotic consumption patterns.

In vitro inferiority of ceftazidime compared with other beta-lactams for viridans group Streptococcus bacteremia in pediatric oncology patients: implications for antibiotic choices.

Viridans group Streptococcus (VGS) is a leading cause of bacteremia in pediatric oncology patients, primarily in children with acute myeloid leukemia or after hematopoietic stem cell transplantation. We retrospectively identified all positive blood cultures in oncology patients at the British Columbia Children's Hospital for a period of 54 months. VGS was the second most commonly isolated pathogen, present in 19% of all the positive blood cultures. Susceptibility analysis of 46 VGS isolates from that period was performed using the Etest method for penicillin, cefotaxime, ceftazidime, and piperacillin/tazobactam. The geometric mean minimal inhibitory concentration for ceftazidime was found to be 9 to 12-fold higher than for any other beta-lactam antibiotic. Penicillin resistance was of 13% with an additional 20% of samples with intermediate susceptibility. The study underscores the prevalence of VGS bacteremia in pediatric patients, especially with acute myeloid leukemia or postallogeneic hematopoietic stem cell transplantation, and the in vitro inferiority of ceftazidime compared with other beta-lactams in that context. We conclude that monotherapy with ceftazidime, or its use along with an aminoglycoside, is not an optimal therapy in pediatric oncology patients with febrile neutropenia.

Bloodstream infections in pediatric ECLS: usefulness of daily blood culture monitoring and predictive value of biological markers. The British Columbia experience.

INTRODUCTION: The incidence of bloodstream infection (BSI) in extracorporeal life support (ECLS) is reported between 0.9 and 19.5%. In January 2006, the Extracorporeal Life Support Organization (ELSO) reported an overall incidence of 8.78% distributed as follows: respiratory: 6.5% (neonatal), 20.8% (pediatric); cardiac: 8.2% (neonatal) and 12.6% (pediatric). METHOD: At BC Children's Hospital (BCCH) daily surveillance blood cultures (BC) are performed and antibiotic prophylaxis is not routinely recommended. Positive BC (BC+) were reviewed, including resistance profiles, collection time of BC+, time to positivity and mortality. White blood cell count, absolute neutrophile count, immature/total ratio, platelet count, fibrinogen and lactate were analyzed 48, 24 and 0 h prior to BSI. A univariate linear regression analysis was performed. RESULTS: From 1999 to 2005, 89 patients underwent ECLS. After exclusion, 84 patients were reviewed. The attack rate was 22.6% (19 BSI) and 13.1% after exclusion of coagulase-negative staphylococci (n = 8). BSI patients were significantly longer on ECLS (157 h) compared to the no-BSI group (127 h, 95% CI: 106-148). Six BSI patients died on ECLS (35%; 4 congenital diaphragmatic hernias, 1 hypoplastic left heart syndrome and 1 after a tetralogy repair). BCCH survival on ECLS was 71 and 58% at discharge, which is comparable to previous reports. No patient died primarily because of BSI. No BSI predictor was identified, although lactate may show a decreasing trend before BSI (P = 0.102). CONCLUSION: Compared with ELSO, the studied BSI incidence was higher with a comparable mortality. We speculate that our BSI rate is explained by underreporting of "contaminants" in the literature, the use of broad-spectrum antibiotic prophylaxis and a higher yield with daily monitoring BC. We support daily surveillance blood cultures as an alternative to antibiotic prophylaxis in the management of patients on ECLS.

Is the healthy middle ear a normally sterile site?

OBJECTIVE: To systematically evaluate the presumption that the healthy middle ear becomes colonized with organisms via the patent eustachian tube using modern microbiologic techniques. STUDY DESIGN: Sterile saline washings were obtained from the middle ear of patients in a prospective fashion. SETTING: Tertiary/quaternary referral centers. PATIENTS: Pediatric and adult patients undergoing cochlear implantation surgery. INTERVENTION(S): Standard bacterial and viral cultures, and nucleic acid amplification techniques. MAIN OUTCOME MEASURE(S): Identification of organisms. RESULTS: Specimens were obtained from 13 children and 9 adults. No organisms were identified in any of the specimens, either through standard culture or PCR testing. CONCLUSION: The presumption that the healthy middle ear is colonized by bacteria from the nasopharynx is unsubstantiated.

An evaluation of a rapid real time polymerase chain reaction assay for detection of group B streptococcus as part of a neonatal group B streptococcus prevention strategy.

OBJECTIVE: To evaluate the sensitivity, specificity, and feasibility of a rapid real-time polymerase chain reaction (PCR) test for group B streptococcus (GBS) completed during labour, compared with the standard culture test performed at 35 to 37 weeks' gestation. METHODS: Women presenting to the maternity unit for term vaginal delivery had two vaginal/rectal samples collected. One swab was tested using a rapid PCR method (IDI-Strep B, Infectio Diagnostic [IDI] Inc., Sainte-Foy QC ), and the other was cultured after enrichment (intrapartum culture). Comparisons were made between these results and those of a culture-based screen at 35 to 37 weeks' gestation. RESULTS: Of the 190 women enrolled, 85% had results of the standard screen at 35 to 37 weeks available for comparison. The sensitivity and specificity of the standard 35- to 37-week screen were 84.3% (95% confidence interval [CI], 71.4-93.0) and 93.2% (95% CI 86.5-97.2) respectively, whereas the sensitivity and specificity of the rapid PCR were 90.7% (95% CI 79.7-96.9) and 97.6% (95% CI 93.1-99.5), respectively. The median reporting time for the rapid PCR test was 99 minutes (range 50-255). Results were available more than four hours before delivery in 81% of cases. CONCLUSION: In this Canadian centre, a rapid PCR test done at the time of labour (IDI-Strep B) demonstrated high sensitivity and specificity, comparable to the 35- to 37-week screen. The time to reporting results was acceptably short, allowing for timely administration of intrapartum prophylactic antibiotics.

Our patients do not need endocarditis prophylaxis for genitourinary tract procedures: insights from the 2007 American Heart Association guidelines.

The 2007 American Heart Association guidelines for the prevention of infective endocarditis have dramatically reduced both the types of eligible procedures and the types of eligible cardiac lesions that require prophylaxis. Antibiotic prophylaxis to prevent infective endocarditis is not indicated for any patient undergoing obstetric and/or gynaecological procedures, not even for patients with underlying cardiac lesions with the highest risk of developing complications from endocarditis. This sharp departure from previously published guidelines relies on the recognition that endocarditis is more likely to develop from "randomly occurring" bacteremia (e.g., from brushing teeth) than from invasive procedures and that antibiotic prophylaxis has not been proven to be effective. A short discussion on enterococcal infections associated to obstetric and gynaecological procedures and therapeutic implications is presented.