whole-genome-sequencing-candida-glabrata-for-detection-markers

Whole Genome Sequencing of <em>Candida glabrata</em> for Detection of Markers of Antifungal Drug Resistance

Candida glabrata can rapidly acquire mutations that result in drug resistance, especially to azoles and echinocandins. Identification of genetic mutations ...

St. Vincent's Hospital

Further evaluation of the MRSA-Screen kit for rapid detection of methicillin resistance.

We report a case of Veillonella parvula lumbar discitis and secondary bacteremia confirmed by molecular characterization of the 16S rRNA genes. Identification of the organism was essential for an appropriate choice of antimicrobial therapy following the failure of empirical flucloxacillin. Veillonella spp. are normal flora of the gastrointestinal tract, raising the possibility that an endoscopy and colonoscopy performed 8 weeks prior to presentation, during which small intestinal and rectal biopsies were obtained, was the portal of entry. This case highlights the importance of obtaining a microbiologic diagnosis, particularly in patients who previously have had procedures involving instrumentation.

Veillonella parvula discitis and secondary bacteremia: a rare infection complicating endoscopy and colonoscopy?

Candidaemia in critically-ill intensive care unit (ICU) patients is associated with high crude mortality. Determinants of mortality--particularly those amenable to potential modification--are incompletely defined.

Determinants of mortality in non-neutropenic ICU patients with candidaemia.

Colonization with Candida species is an independent risk factor for invasive candidiasis (IC), but the minimum and most practicable parameters for prediction of IC have not been optimized. We evaluated Candida colonization in a prospective cohort of 6,015 nonneutropenic, critically ill patients. Throat, perineum, and urine were sampled 72 h post-intensive care unit (ICU) admission and twice weekly until discharge or death. Specimens were cultured onto chromogenic agar, and a subset underwent molecular characterization. Sixty-three (86%) patients who developed IC were colonized prior to infection; 61 (97%) tested positive within the first two time points. The median time from colonization to IC was 7 days (range, 0 to 35). Colonization at any site was predictive of IC, with the risk of infection highest for urine colonization (relative risk [RR]=2.25) but with the sensitivity highest (98%) for throat and/or perineum colonization. Colonization of ≥2 sites and heavy colonization of ≥1 site were significant independent risk factors for IC (RR=2.25 and RR=3.7, respectively), increasing specificity to 71% to 74% but decreasing sensitivity to 48% to 58%. Molecular testing would have prompted a resistance-driven decision to switch from fluconazole treatment in only 11% of patients infected with C. glabrata, based upon species-level identification alone. Positive predictive values (PPVs) were low (2% to 4%) and negative predictive values (NPVs) high (99% to 100%) regardless of which parameters were applied. In the Australian ICU setting, culture of throat and perineum within the first two time points after ICU admission captures 84% (61/73 patients) of subsequent IC cases. These optimized parameters, in combination with clinical risk factors, should strengthen development of a setting-specific risk-predictive model for IC.

Candida colonization as a risk marker for invasive candidiasis in mixed medical-surgical intensive care units: development and evaluation of a simple, standard protocol.

Respiratory syncytial virus (RSV) causes serious respiratory tract infections in lung transplant (LTx) recipients, is associated with development of bronchiolitis obliterans syndrome, and has no proven effective therapy. We evaluated the efficacy, safety, and cost-effectiveness of oral ribavirin for the treatment of RSV infection after LTx.

Oral ribavirin for respiratory syncytial virus infection after lung transplantation: Efficacy and cost-efficiency.

Posaconazole therapeutic drug monitoring (TDM) is recommended to promote effective antifungal prophylaxis, but its utility has yet to be optimized. Breakthrough invasive fungal infections have been reported with serum concentrations <700 mcg/L, but there is little evidence to determine the optimal serum concentration for efficacy or concentrations associated with toxicity. Challenges for effective monitoring are greater in settings without posaconazole TDM facilities because of the long turnaround time before receipt of results.

Posaconazole Therapeutic Drug Monitoring in a Regional Hospital Setting.

Antifungal susceptibilities of non-Aspergillus filamentous fungal pathogens cannot always be inferred from their identification. Here we determined, using the Sensititre(®) YeastOne(®) YO10 panel, the in vitro activities of nine antifungal agents against 52 clinical isolates of emergent non-Aspergillus moulds representing 17 fungal groups in Australia. Isolates comprised Mucorales (n = 14), Scedosporium/Lomentospora spp. (n = 18) and a range of hyaline hyphomycetes (n = 9) and other dematiaceous fungi (n = 11). Excluding Verruconis gallopava, echinocandins demonstrated poor activity (MICs generally >8 mg/L) against these moulds. Lomentospora prolificans (n = 4) and Fusarium spp. (n = 6) demonstrated raised MICs to all antifungal drugs tested, with the lowest being to voriconazole and amphotericin B (AmB), respectively (geometric mean MICs of 3.4 mg/L and 2.2 mg/L, respectively). All Scedosporium apiospermum complex isolates (n = 14) were inhibited by voriconazole concentrations of ≤0.25 mg/L, followed by posaconazole and itraconazole at ≤1 mg/L. Posaconazole and AmB were the most active agents against the Mucorales, with MIC90 values of 1 mg/L and 2 mg/L, respectively, for Rhizopus spp. For dematiaceous fungi, all isolates were inhibited by itraconazole and posaconazole concentrations of ≤0.5 mg/L (MIC90, 0.12 mg/L and 0.25 mg/L, respectively), but voriconazole and AmB also had in vitro activity (MIC90, 0.5 mg/L and 1 mg/L, respectively). Differences in antifungal susceptibility within species and between species within genera support the need for testing individual patient isolates to guide therapy. The Sensititre(®) YeastOne(®) offers a practical alternative to the reference methodology for susceptibility testing of moulds.

Antifungal susceptibilities of non-Aspergillus filamentous fungi causing invasive infection in Australia: support for current antifungal guideline recommendations.

 Delayed antifungal therapy for invasive candidiasis (IC) contributes to poor outcomes. Predictive risk models may allow targeted antifungal prophylaxis to those at greatest risk.

Problematic Dichotomization of Risk for Intensive Care Unit (ICU)-Acquired Invasive Candidiasis: Results Using a Risk-Predictive Model to Categorize 3 Levels of Risk From a Multicenter Prospective Cohort of Australian ICU Patients.

Article	Year
Further evaluation of the MRSA-Screen kit for rapid detection of methicillin resistance. Journal of clinical microbiology\| PubMed ID: 10610377	1999
Veillonella parvula discitis and secondary bacteremia: a rare infection complicating endoscopy and colonoscopy? Journal of clinical microbiology\| PubMed ID: 17108070	2007
Determinants of mortality in non-neutropenic ICU patients with candidaemia. Critical care (London, England)\| PubMed ID: 19594912	2009
Candida colonization as a risk marker for invasive candidiasis in mixed medical-surgical intensive care units: development and evaluation of a simple, standard protocol. Journal of clinical microbiology\| PubMed ID: 25673797	2015
Oral ribavirin for respiratory syncytial virus infection after lung transplantation: Efficacy and cost-efficiency. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation\| PubMed ID: 25753833	2015
Posaconazole Therapeutic Drug Monitoring in a Regional Hospital Setting. Therapeutic drug monitoring\| PubMed ID: 27548694	2016
Antifungal susceptibilities of non-Aspergillus filamentous fungi causing invasive infection in Australia: support for current antifungal guideline recommendations. International journal of antimicrobial agents\| PubMed ID: 27562696	2016
Problematic Dichotomization of Risk for Intensive Care Unit (ICU)-Acquired Invasive Candidiasis: Results Using a Risk-Predictive Model to Categorize 3 Levels of Risk From a Multicenter Prosp... Clinical infectious diseases : an official publication of the Infectious Diseases Society of America\| PubMed ID: 27601224	2016

Deborah J. Marriott

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