Innovation, Education, Quality Assessment, Continual Improvement P l e ur al fl ui d : Stre pt oc oc cu s pne u mo n i a e –multi re sistan t strain “susceptible” by 12/15 reference labs. Given that vancomycin reporting may depend on the This sample simulated a pleural fluid from a 1 penicillin and/or cephalosporin results, where Virtually all labs isolated and year old patient with empyema. The sample consensus was not achieved, the CMPT com- correctly identified Strepto- was sent to category A laboratories, which were mittee elected not to grade the vancomycin coccus pneumoniae and were requested to process and report as per their results. The rest of the antimicrobial agents given a grade of 4. usual protocol. Participants were expected to were not graded due to lack of consensus As discussed above, there isolate, identify Streptococcus pneumoniae and perform antimicrobial susceptibility testing. According to the CLSI guidelines, the agents the reported MICs and the that should be primarily tested and reported susceptibility interpretations (Group A) are erythromycin, penicillin and trime- throprim-sulphamethoxazole (SXT). The results ceftriaxone, therefore these hemolytic colonies on blood agar plates) of for these agents are summarized in Table 2. Streptococcus pneumoniae, viable for 5 days. All laboratories testing SXT and erythromycin Many labs, including the refer- reported the strain as resistant to both agents. Susceptibility reports on penicillin were ambigu- ous: 49% reported it as “resistant, 16% as mycin, clindamycin, SXT or “intermediate”, and the remaining 34% re- Reference Labs: 15/15 labs reported ported it as “susceptible”. Many laboratories were not graded. Labs which S.pneumoniae. The identification component of had interpreted the results as “resistant” even did report these agents re- though the MIC values were 1, 2, 3 or 4ug/mL. ported them all correctly as According to the CLSI guidelines, for parenteral resistant. All laboratories correctly identified the isolate as treatment of non-meningitis isolates, values of Streptococcus pneumoniae and received a “susceptible” and values of 4 ug/mL should be However, vancomycin report- interpreted as intermediate. Two labs reported ing depends on the results of The isolate was intended to have a penicillin an MIC value of ≥2 ug/mL (both labs tested penicillin and/or cepha- MIC of 4 ug/mL, which for parenteral treatment using Vitek 2). In non-meningeal isolates, MIC losporin test results where of nonmeningitis is interpreted as intermediate. value of ≥2 ug/mL for penicillin could be inter- For non-menigitis isolates, the cefotaxime and preted as S, I, or even R. Only two labs met the Therefore, vancomycin results ceftriaxone should have an MIC of 2 ug/mL to criteria to report this isolate as “resistant” to were ungraded this time. be interpreted as intermediate. The isolate was penicillin (MIC values of 8 and 12 ug/mL). resistant to trimethoprim-sulfamethoxazole, The differences in penicillin results and inter- erythromycin, clindamycin and tetracycline and pretations are most likely due to several fac- susceptible to vancomycin, levofloxacin and tors. There is a narrow margin for error when lates and ensure that vanco- determining the MIC of an isolate with interme- Consensus was only achieved for vancomycin diate susceptibility using the current methods. reported when the penicillin susceptibility testing which was reported Selecting the correct interpretation maybe con- fusing because the CLSI guidelines provide dif- ferent interpretations for the same MIC value. R. The interpretations are based on whether the isolate is associated with meningitis or not and for penicillin (and cefuroxime) as to whether the treatment is oral versus parenteral. Given the clinical setting, CMPT expected labs to choose the penicillin MIC values. The confusion may CMPT Clinical Bacteriology Program February 2010 M094-5 Table 2. Results for Group A antimicrobial agents the routine reporting of fluoro-quinolone results in children choose to report fluoroqui-nolone results, then they S: susceptible; I: intermediate; R: resistant; SXT: trimethroprim-sulfamethoxazole; * see discussion in text. should include a cautionary note indicating that fluorqui- have been compounded by the CLSI recommen- lin, there were notable differences amongst nolones’ safety in children dation that both meningitis and non-meningitis laboratories in the reporting of results for ceftri- interpretations must be reported, even if iso- axone and cefotaxime. The intended MIC for both cefotaxime and ceftriaxone was 2 ug/mL Labs and their computer systems are expected and the correct interpretation for this non- to present all this information in a fashion that meningitis isolate is intermediate. The MIC can be readily understood by clinicians. Simi- values reported by labs varied between 1 and 4 larly, the CMPT online system for entering re- ug/ml, again highlighting the narrow limits for sults was not built to accommodate reporting of error when determining the MIC of an isolate multiple interpretations of a given penicillin with intermediate susceptibility. One dilution MIC. Finally, given that many labs obtained, on factor either way would change the interpreta- the same isolate, an intermediate or resistant tion. All, but one, of the laboratories reporting susceptibility result to the third generation cefotaxime or ceftriaxone as “resistant” ob- cephalosporins (cefotaxime/ceftriaxone), there tained MIC values that should have been inter-may have been a reluctance to report the peni- preted as “intermediate” for non-meningitis CMPT has observed that a cillin as more susceptible, regardless of the isolates. The only lab that “correctly” inter- preted their result to cefotaxime as “resistant” laboratories is to mix sam- obtained a MIC value of 4 ug/mL. One labora- Table 3 summarizes the results for testing tory reported the interpretation of the MIC val- group B agents (primary test, report selectively). ues backwards when given the interpretation All laboratories that reported vancomycin re- for meningitis and non-meningitis isolates. ported it as susceptible. All laboratories report- ing clindamycin and tetracycline reported the Laboratories are advised to carefully review the form, which would help pre- isolate as resistant. The isolate was interpreted CLSI guidelines and, as per the previous multi- as susceptible to levofloxacin by 20 labs and resistant S. pneumoniae critique 1 (M082-3), many of them appropriately indicated that they provide both meningitis and non-meningitis would not report the agent due to the age of the interpretations when reporting susceptibility results on non-meningitis isolates. Moreover, it is important that the interpretations be clearly Just as with the testing and reporting of penicil- differentiated on the report and that an ex- Table 3. Results for Group B antimicrobial agents. processed as routine sam-ples even when there is a *Three labs reported R with MIC values of 1.5 and 2.0ug/mL. These values should have been inter- preted as I according to CLSI guidelines for nonmeningitis isolates. **Three labs reported I with MIC values of 1.0ug/mL and 2 labs reported R with MIC values of 2.0ug/mL. At least 54/76 labs clearly reported interpreta-tion to ceftriaxone or cefotaxime. CMPT Clinical Bacteriology Program February 2010 M094-5 grossly purulent fluid in the pleural cavity, com-plicated the cases of approximately 0.6% of “Note: The interpretation of susceptibility re- children with bacterial pneumonia. 6 However, sults for penicillin, cefotaxime and ceftriaxone the incidence of parapneumonic effusions and to Streptococcus pneumoniae varies depending emypyema is increasing simultaneously with a MDR is defined as resistance on the presence or absence of meningitis. In rise in antibiotic resistant organisms, despite to ≥ 3 antibiotic classes. In the setting of possible infection of the central reductions in pneumococcal pneumonia Canada, the proportion of nervous system, clinicians should use the inter- achieved through use of the pneumococcal MDR isolates increased from conjugate vaccine. Perhaps, this is because 2.7% to 8.8% from 1997 to empyema is frequently associated with pneu- mococcal serotypes not included in the stan- dard conjugate vaccine. 7 Underlying diseases cocci in Canada (CROSS) be-including cystic fibrosis, prematurity, congenital heart disease, cerebral palsy, Down’s syndrome pneumococcal isolates exhib- Pneumococci grow readily on blood agar plates and immunodeficiencies may increase the risk ited MDR. 10 Over this time in a CO2 incubator at 37°C. S pneumoniae colo- nies are α-haemolytic and often umbilicate be- Susceptibility testing results for Streptococcus cause of autolysis. The organism maybe identi- pneumoniae isolates (n = 2,279) from eight fied using classical test methods such as: cata- European countries, examined in the Pneumo- lase, bile esculin, Taxo P, NaCl, bile solubility, World Study from 2001 to 2003, demonstrates PYR and latex agglutination (Pneumoslide); or that 24.6% of S. pneumoniae isolates were not by commercial systems (Vitek2, MS, API) or susceptible to penicillin G and 28.0% were re- rarely by molecular methods. Cultures from sistant to macrolides. The prevalence of resis- sputum, blood and other tissue sites should be tance varied widely between European coun- obtained before empirical antibiotic therapy is tries, with the highest rates of penicillin G and macrolide resistance reported from Spain and France. 8 Another Canadian survey of invasive S.pneumoniae isolates found that 16.85% were Streptococcus pneumoniae (pneumococcus) not susceptible to penicillin, 5.4% were highly resistant to penicillin and 14.1% had reduced nia, meningitis and otitis media. Infections with susceptibility to erythromycin. All isolates were this microorganism are associated with signifi- susceptible to telithromycin. Only 6 isolates were resistant to levofloxacin and gatifloxacin. Incidence of invasive pneumococcal disease Of these, 5 strains had intermediate suscepti- (IPD) (ie, bacterial pneumonia and bacteremia) bility to moxifloxacin and 1 was considered sus- varies substantially by age, genetic background, socioeconomic status, immune status and geo- Fluoroquinolone resistance in S. pneumoniae graphical location. The World Health Organiza- has increased significantly in Canada through- tion estimates that ~1.6 million people, includ- out the past decade. Resistance rates were ing up to 1 million children aged <5 years, die highest in the elderly and lowest in children, of IPD every year, with developing countries with significant increases noted in all age cate- gories. The low resistance in children have pre- Risk factors for community-acquired pneumonia viously been associated with the limited use of (CAP) are numerous and varied and include fluoroquinolones in children. 12 Flouroquinolone extremes of age, underlying co-morbid illness resistance was discussed in a previous CMPT (such as chronic cardiovascular disease, COPD, critique M063-3. 13 Over the last 20 years, Ca- asthma and more recently, concomitant infec- nadian pneumococcal surveillance studies have tion with the HIV), defects in host immune re- documented a steady rise in macrolide resis- sponses, low socioeconomic status, malnutri- tance. Nationally, macrolide resistance in- creased from 3.7% in 1995 to 19.0% in 2005. 14 S.pneumoniae is the most common pathogen causing parapneumonic effusions. 5 Prior to 1980, empyema, defined as the presence of CMPT Clinical Bacteriology Program February 2010 M094-5 pleural effusion and empyema in children. Treatment of S.pneumoniae empyema requires Review of a 19-year experience,1962-1980. Clin Pediatr 1983; 22:414. both antibiotics and adequate drainage. 7. Li ST, Tancredi DJ. Empyema hospitaliza- Emperic therapy is typically with a third genera- tions increased in US children despite pneu- tion cephalosporin such as cefotaxime or ceftri- axone and therapy should be modified on the 2010; 125:26. basis of the susceptibility results 15. In the case 8. Reinert RR, Reinert S, van der Linden M, of an isolate that is exhibiting low level resis- Cil MY, Al-Lahham A, Appelbaum P. Antim-icrobial susceptibility of Streptococcus pneu- tance to penicillin and cephalosporins and that moniae in eight european countries from is resistant to other commonly used classes of antibiotics (ie. clindamycin, erythromycin and ther. 2005;49:2903-2913. SXT) the addition of parenteral vancomycin 9. Zhanel GG, Palatnick L, Nichol KA, Bellyou maybe appropriate. Pediatric infectious disease T, Low DE, Hoban DJ. Antimicrobial resis- consultation could assist in determining the tance in respiratory tract Streptococcus pneumoniae isolates: Results of the Cana- role of newer agents such as linezolid, telithro- dian respiratory organism susceptibility mycin, or moxifloxacin. The use of such agents to treat multi-resistant strains in pediatrics has been limited and their safety has not been es- 10. Zhanel GG, Wang X, Nichol K, et al. Mo- tablished. It has been recommended that intra- lecular characterisation of Canadian paediat- venous antibiotics be continued for five days ric multidrug-resistant Streptococcus pneu-after resolution of fever and oral therapy for at moniae from 1998-2004. Int J Antimicrob Agents. 2006;28:465-471. 11. Davidson RJ, Melano R, Forward KR. An- Adequate drainage is very important and there timicrobial resistance among invasive iso- are a variety of therapeutic options including lates of Streptococcus pneumoniae collected across Canada. Diagn Microbiol Infect Dis. thoracentesis, thoracostomy tube, fibrinolytics, 2007;59:75-80. video-assisted thorascopic surgery and thora- 12. Adam HJ, Hoban DJ, Gin AS, Zhanel GG. cotomy. Generally, treatment measures are Association between fluoroquinolone usage used in a step-wise fashion. Although one sys- and a dramatic rise in ciprofloxacin-resistant tematic review of pediatric empyema outcomes Streptococcus pneumoniae in Canada, demonstrated that primary operative therapy 1997–2006. Int J Antimicrob Agents. compared favourably with nonoperative ap- 2009;34:82-85. 13. CMPT M063-3 Sputum: Streptococcus proaches16. Prospective randomized trials are pneumoniae (multi-resistant strain). CMPT required to identify the optimal therapy for each Clinical Bacteriology Critiques. November 14. Karlowsky JA, Lagacé-Wiens PRS, Low DE, Zhanel GG. Annual macrolide prescrip- 1. CMPT. M082-3 sputum: Streptococcus tion rates and the emergence of macrolide pneumoniae (multi-resistant strain). CMPT resistance among Streptococcus pneumo- Clinical Bacteriology Critiques. 2008;August niae in Canada from 1995 to 2005. Int J ment and prognosis of parapneumonic effu- 2. van der Poll T, Opal SM. Pathogenesis, sion and empyema in children. In: Sexton DJ treatment, and prevention of pneumococcal 16. Avansino JR, Goldman B, Sawin RS and 3. Werno AM, Murdoch DR. Medical microbi- Flum DR. Primary operative versus nonopera- ology: Laboratory diagnosis of invasive pneu- tive therapy for pediatric empyema: a meta- mococcal disease. Clin Infect Dis. analysis. Pediatrics 2005;115:1652-1659. 2008;46:926-932. 4. Feldman C, Anderson R. New insights into p n e u m o c o c c a l d i s e a s e . R es p i r o l o g y . 2009;14:167-179. 5. Janahi IA, Fakhoury K. 2010. Epidemiol-ogy; clinical presentation; and evaluation of parapneumonic effusion and empyema in children. In: Sexton DJ ed. Uptodate. 6. Chonmaitree T, Powell KR. Parapneumonic

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Oral Session #5 (Sat am, 10:45-11:45) Scientific Oral Presentation Session 5  Moderator: Dr. Brenna Anderson  High Resolution Profiling of the Vaginal Microbiome of Healthy, Reproductive Aged Canadian Women A Multicenter, Randomized, Placebo controlled, Parallel‐Group, Double Blinded Study to Compare the Therapeutic of 3 Single Vaginal Doses o

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