Mohammed Qutub

Background: Candidaemia is the most common form of invasive candidiasis. Resistant Candida blood stream infection (BSI) is rising, with limitations on the development of broader-spectrum antifungal agents worldwide. Our study aimed to identify the occurrence of antifungal-resistant candidaemia and the distribution of these species, determine the risk factors associated with antifungal resistance and evaluate the association of antifungal-resistant candidaemia with the length of intensive care unit (ICU) and hospital stay and with 30-day mortality. Methods: A retrospective cohort study was conducted at King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia. Adult patients diagnosed with candidaemia from January 2006 to December 2017 were included. Results: A total of 196 BSIs were identified in 94 males (49.74%) and 95 females (50.26%). C. glabrata was the most commonly isolated Candida species, with 59 (30%), followed by C. albicans with 46 (23%). Susceptibility data were available for 122/189 patients, of whom 26/122 (21%) were resistant to one or more antifungals. C. parapsilosis with available sensitivity data were found in 30/122 isolates, of which 10/30 (33%) were resistant to fluconazole. Risk factors significantly associated with antifungal-resistant candidaemia included previous echinocandin exposure (odds ratio (OR) =1.38; 95% confidence interval (CI) (1.02–1.85); P = 0.006) and invasive ventilation (OR = 1.3; 95% CI (1.08–1.57); P = 0.005). The median length of ICU stay was 29 days [range 12–49 days] in the antifungal-resistant group and 18 days [range 6.7–37.5 days] in the antifungal-sensitive group (P = 0.28). The median length of hospital stay was 51 days [range 21–138 days] in the antifungal-resistant group and 35 days [range 17–77 days] in the antifungal-sensitive group (P = 0.09). Thirty-day mortality was 15 (57.7%) and 54 (56.25%) among the antifungal-resistant and antifungal-sensitive groups, respectively (OR = 1.01; 95% CI (0.84–1.21); P = 0.89). Conclusions: Our results indicate a high frequancy of non- C. albicans candidaemia. The rise in C. parapsilosis resistance to fluconazole is alarming. Further studies are required to confirm this finding.

Carbapenem-resistant Enterobacteriaceae (CRE) represent an important global threat. The aim of this study is to describe the clinical course and outcomes of patients with CRE infections treated with ceftazidime-avibactam (CAZ-AVI) compared to patients treated with other agents. A retrospective cohort study of patients with established CRE infections from January 2017 until August 2018 was conducted. All patients who received CAZ-AVI and all cultures with carbapenem-resistant isolates were screened. We compared patients who received CAZ-AVI for CRE infections with patients who received other agents. A total of 38 consecutive patients with CRE infections were identified. Age and baseline comorbidities were similar between the two groups. The median time from admission to isolation of CRE culture was 22.5 days in the CAZ-AVI group and 17 days in the comparative group (P = 0.7). The incidence of CRE bacteremia was similar between the two groups: 7 patients (70%) in the CAZ-AVI group and 15 patients (53.6%) in the comparative group (P = 0.47). The most common type of CRE infections in both groups was hospital acquired pneumonia (HAP). Klebsiella pneumoniae was the predominant pathogen in both groups. A carbapenemase gene was detected in 35 (92%) patients; the OXA-48 gene was the predominant gene identified in 28 (74%) isolates. Eight out of ten patients in the CAZ-AVI group and fifteen out of twenty-eight in the comparative group achieved clinical remission (P = 0.14). After thirty days, all-cause mortality was observed in five patients in the CAZ-AVI group and 16 patients in the comparative group, accounting for 50 and 57% respectively. In patients with established OXA-48-type CRE infection, CAZ-AVI is a reasonable alternative to standard therapy. These findings need to be confirmed in prospective studies.

The aim of this study was to evaluate the effectiveness of a two-step algorithm for the detection of Clostridium difficile infection. Setting and Design: A two-step testing algorithm was evaluated for testing stool samples from patients suspected of Clostridium difficile infection (CDI). A total of 103 stool specimens were tested using the C. diff Quik Chek Complete enzyme immunoassay (EIA) test and the Xpert C. difficile PCR test. A two-step algorithm was implemented, and data from 3518 patient samples tested during a two-year period after implementation were analyzed to evaluate the effectiveness. The sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of the Quik Chek Complete EIA test were calculated using the Xpert C. difficile PCR test as a reference method. The sensitivity, specificity, PPV, and NPV of the Quik Chek Complete EIA test for C. difficile toxin were 46.7%, 100%, 100%, and 91%, respectively. The two-step algorithm, which combined the Quik Chek Complete EIA with Xpert C. difficile PCR, improved the sensitivity and also provided rapid detection. When algorithm-based testing was performed daily, there was a 66% reduction in turnaround time compared to batch testing using a lengthy ELISA procedure. Postimplementation data analysis showed that almost 89% of the samples could be reported immediately by initial screening with Quik Chek Complete EIA. Only 11% of the samples gave discrepant results and required PCR confirmation. According to our results, the two-step algorithm is an effective tool for the rapid and reliable detection of toxigenic C. difficile from stool samples.

Introduction: The emergence of carbapenemaseresistant Enterobacteriaceae (CRE) is an imminent threat to public health obligating, the development of novel β-lactam/β-lactamase inhibitors to combat its relentless spread, an example of which is ceftazidime-avibactam (CAZAVI). Since its introduction in 2015, worldwide data continues to pour in describing different mechanisms of treatment failure, primarily mediated by members of metallo-β-lactamase (MBL), Klebsiella pneumoniae carbapenemase (KPC), and oxacillinase (OXA) enzymes. Case Report: We report a case of a previously healthy 22-year-old male who was admitted to the critical care burn unit as a case of third-degree chemical burn injury involving 80% of his body surface area. His tissue cultures grew Klebsiella pneumoniae which was resistant to CAZ-AVI. Further analysis of resistance patterns by Xpert® Carba-R detected the presence of both NDM (New Delhi metallo-β-lactamase) and OXA-48 mutation genes. Conclusion: OXA-48-mediated carbapenemase resistance is a regional threat in the Middle East and it is increasingly expanding in terms of its epidemiology and activity against novel antimicrobials. This activity is primarily mediated by mutant doubling and plasmid adaptation and can be horizontally acquired by coexistence with other resistant genes. We are reporting the first OXA-48-mediated CAZ-AVI resistance in the western region of Saudi Arabia which raises the concern about CRE spread in the country. Necessitating wiser use of available genotypic testing coupled with strict adherence of infection control protocols and antimicrobial stewardship programs.