Characteristics of polymerase chain reaction-positive syphilis cases in Manitoba, Canada, 2017 to 2020: Demographic analysis, specimen types, and Treponema pallidum gene targets.

BACKGROUND: A resurgence of syphilis infections has been described in a number of countries including Canada in the last decade. METHODS: This study identified polymerase chain reaction (PCR) positive syphilis cases based on detection of Treponema pallidum genes (polA, tpp47, and bmp) in 3,350 clinical specimens obtained from patients in the province of Manitoba, Canada between 2017 and 2020. Patient demographics were obtained from specimen requisition forms. RESULTS: PCR identified 740 syphilis cases: 718 were adolescents and adults, while 22 were congenital syphilis cases. For non-congenital syphilis investigation, the clinical specimens with the highest yield of positive PCR results were genital (632), oral (73), and anal (55), while for congenital syphilis, they were nasal or nasopharyngeal secretions (20), followed by blood (5) and umbilical cord (4). Female syphilis cases appeared younger (61.7% between 14 and 29 years), while male syphilis cases appeared older (58.4% between 30 and 65 years). Although, overall more syphilis cases (62.7%) occurred in the urban cities; the proportion of urban cases showed a significant decline from 87.0% in 2017 to 55.6% in 2020, while in rural regions it increased from 13.0% in 2017 to 44.4% in 2020. Most (98.8%) PCR- positive specimens were found to contain all three T. pallidum genes and 99.8% also displayed the macrolide resistance genotype. CONCLUSIONS: This study identified the clinical specimen types and T. pallidum genes most suitable for PCR diagnosis of syphilis. Changing demographics of cases were noted over time.

HISTORIQUE: Depuis dix ans, les infections par la syphilis sont en recrudescence dans plusieurs pays, y compris le Canada. MÉTHODOLOGIE: La présente étude relève les cas positifs à l'amplification en chaîne par polymérase (PCR) d'après la détection des gènes du Treponema pallidum (polA, tpp47 et bmp) dans 3 350 échantillons cliniques prélevés auprès de patients de la province du Manitoba, au Canada, entre 2017 et 2020. Les caractéristiques démographiques des patients sont tirées des formulaires de réquisition des prélèvements. RÉSULTATS: Le test PCR a permis de détecter 740 cas de syphilis, soit 718 chez des adolescents et des adultes et 22 cas de syphilis congénitale. Pour ce qui est des examens de la syphilis non congénitale, les échantillons cliniques donnant le plus fort taux de résultats positifs au test PCR ont été prélevés dans la région génitale (632), orale (73) et anale (55), tandis qu'à l'égard des cas de syphilis congénitale, ils provenaient des sécrétions nasales ou nasopharyngées (20), suivis du sang (5) et du cordon ombilical (4). La syphilis se manifestait chez des femmes plus jeunes (61,7 % entre 14 et 29 ans) et plus tard chez les hommes (58,4 % entre 30 et 65 ans). Même si, dans l'ensemble, plus de cas de syphilis (62,7 %) se déclaraient en région urbaine, cette proportion a connu un recul important, passant de 87,0 % en 2017 à 55,6 % en 2020, tandis que la proportion des cas en région rurale a progressé de 13,0 % en 2017 à 44,4 % en 2020. La plupart des échantillons ayant obtenu un résultat positif au test PCR (98,8 %) contenaient les trois gènes du T. pallidum, et 99,8 % possédaient également le génotype de résistance aux macrolides. CONCLUSIONS: La présente étude a relevé les types d'échantillons cliniques et les gènes de T. pallidum les plus appropriés pour le diagnostic de syphilis par test PCR. On constate une évolution de la démographie des cas au fil du temps.

Comparison of PCV-10 and PCV-13 vaccine coverage for invasive pneumococcal isolates obtained across Canadian geographic regions, SAVE 2011 to 2017.

To assess the coverage of invasive Streptococcus pneumoniae by pneumococcal conjugate vaccines (PCV)-10 and PCV-13 across Canada. In total, 9166 invasive S. pneumoniae isolates were collected as part of the SAVE 2011 to 2017 study. Serotyping was performed by the Quellung reaction and antimicrobial susceptibility testing was performed using CLSI methods. The proportion of both PCV-10 and PCV-13 serotypes decreased significantly (P < 0.0001) from 2011 (26.7% and 48.0%, respectively) to 2017 (11.2% and 26.2%). For central, western, and eastern regions of Canada, PCV-13 provided significantly greater (P < 0.0001) coverage at 33.7% (2060/6110), 23.0% (456/1985), and 36.3% (389/1071), respectively, compared to PCV-10 at 15.4% (939/6110), 10.1% (201/1985), and 15.8% (169/1071) coverage. PCV-13 provided significantly greater coverage (53.3%, 282/529) of multidrug-resistant (MDR) isolates (resistant to ≥3 antimicrobial classes) than PCV-10 (14.6%, 77/529, P < 0.0001). PCV-13 provided significantly greater coverage of invasive S. pneumoniae serotypes, as well as coverage of MDR isolates, than PCV-10.

Omadacycline: A Novel Oral and Intravenous Aminomethylcycline Antibiotic Agent.

Omadacycline is a novel aminomethylcycline antibiotic developed as a once-daily, intravenous and oral treatment for acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP). Omadacycline, a derivative of minocycline, has a chemical structure similar to tigecycline with an alkylaminomethyl group replacing the glycylamido group at the C-9 position of the D-ring of the tetracycline core. Similar to other tetracyclines, omadacycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. Omadacycline possesses broad-spectrum antibacterial activity against Gram-positive and Gram-negative aerobic, anaerobic, and atypical bacteria. Omadacycline remains active against bacterial isolates possessing common tetracycline resistance mechanisms such as efflux pumps (e.g., TetK) and ribosomal protection proteins (e.g., TetM) as well as in the presence of resistance mechanisms to other antibiotic classes. The pharmacokinetics of omadacycline are best described by a linear, three-compartment model following a zero-order intravenous infusion or first-order oral administration with transit compartments to account for delayed absorption. Omadacycline has a volume of distribution (Vd) ranging from 190 to 204 L, a terminal elimination half-life (t½) of 13.5-17.1 h, total clearance (CLT) of 8.8-10.6 L/h, and protein binding of 21.3% in healthy subjects. Oral bioavailability of omadacycline is estimated to be 34.5%. A single oral dose of 300 mg (bioequivalent to 100 mg IV) of omadacycline administered to fasted subjects achieved a maximum plasma concentration (Cmax) of 0.5-0.6 mg/L and an area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) of 9.6-11.9 mg h/L. The free plasma area under concentration-time curve divided by the minimum inhibitory concentration (i.e., fAUC24h/MIC), has been established as the pharmacodynamic parameter predictive of omadacycline antibacterial efficacy. Several animal models including neutropenic murine lung infection, thigh infection, and intraperitoneal challenge model have documented the in vivo antibacterial efficacy of omadacycline. A phase II clinical trial on complicated skin and skin structure infection (cSSSI) and three phase III clinical trials on ABSSSI and CABP demonstrated the safety and efficacy of omadacycline. The phase III trials, OASIS-1 (ABSSSI), OASIS-2 (ABSSSI), and OPTIC (CABP), established non-inferiority of omadacycline to linezolid (OASIS-1, OASIS-2) and moxifloxacin (OPTIC), respectively. Omadacycline is currently approved by the FDA for use in treatment of ABSSSI and CABP. Phase II clinical trials involving patients with acute cystitis and acute pyelonephritis are in progress. Mild, transient gastrointestinal events are the predominant adverse effects associated with use of omadacycline. Based on clinical trial data to date, the adverse effect profile of omadacycline is similar to studied comparators, linezolid and moxifloxacin. Unlike tigecycline and eravacycline, omadacycline has an oral formulation that allows for step-down therapy from the intravenous formulation, potentially facilitating earlier hospital discharge, outpatient therapy, and cost savings. Omadacycline has a potential role as part of an antimicrobial stewardship program in the treatment of patients with infections caused by antibiotic-resistant and multidrug-resistant Gram-positive [including methicillin-resistant Staphylococcus aureus (MRSA)] and Gram-negative pathogens.

42936 pathogens from Canadian hospitals: 10 years of results (2007-16) from the CANWARD surveillance study.

OBJECTIVES: The CANWARD surveillance study was established in 2007 to annually assess the in vitro susceptibilities of a variety of antimicrobial agents against bacterial pathogens isolated from patients receiving care in Canadian hospitals. METHODS: 42 936 pathogens were received and CLSI broth microdilution testing was performed on 37 355 bacterial isolates. Limited patient demographic data submitted with each isolate were collated and analysed. RESULTS: Of the isolates tested, 43.5%, 33.1%, 13.2% and 10.2% were from blood, respiratory, urine and wound specimens, respectively; 29.9%, 24.8%, 19.0%, 18.1% and 8.2% of isolates were from patients in medical wards, emergency rooms, ICUs, hospital clinics and surgical wards. Patient demographics associated with the isolates were: 54.6% male/45.4% female; 13.1% patients aged ≤17 years, 44.3% 18-64 years and 42.7% ≥65 years. The three most common pathogens were Staphylococcus aureus (21.2%, both methicillin-susceptible and MRSA), Escherichia coli (19.6%) and Pseudomonas aeruginosa (9.0%). E. coli were most susceptible to meropenem and tigecycline (99.9%), ertapenem and colistin (99.8%), amikacin (99.7%) and ceftolozane/tazobactam and plazomicin (99.6%). Twenty-three percent of S. aureus were MRSA. MRSA were most susceptible to ceftobiprole, linezolid and telavancin (100%), daptomycin (99.9%), vancomycin (99.8%) and tigecycline (99.2%). P. aeruginosa were most susceptible to ceftolozane/tazobactam (98.3%) and colistin (95.0%). CONCLUSIONS: The CANWARD surveillance study has provided 10 years of reference antimicrobial susceptibility testing data on pathogens commonly causing infections in patients attending Canadian hospitals.