Pan-Echinocandin-Resistant Candida glabrata Bloodstream Infection Complicating COVID-19: A Fatal Case Report.

Coinfections with bacteria or fungi may be a frequent complication of COVID-19, but coinfections with Candida species in COVID-19 patients remain rare. We report the 53-day clinical course of a complicated type-2 diabetes patient diagnosed with COVID-19, who developed bloodstream infections initially due to methicillin-resistant Staphylococcus aureus, secondly due to multidrug-resistant Gram-negative bacteria, and lastly due to a possibly fatal Candida glabrata. The development of FKS-associated pan-echinocandin resistance in the C. glabrata isolated from the patient after 13 days of caspofungin treatment aggravated the situation. The patient died of septic shock shortly before the prospect of receiving potentially effective antifungal therapy. This case emphasizes the importance of early diagnosis and monitoring for antimicrobial drug-resistant coinfections to reduce their unfavorable outcomes in COVID-19 patients.

Direct use of eazyplex® SuperBug CRE assay from positive blood cultures in conjunction with inpatient infectious disease consulting for timely appropriate antimicrobial therapy in Escherichia coli and Klebsiella pneumoniae bloodstream infections.

Objectives: To describe a rapid workflow based on the direct detection of Escherichia coli (Ec) and Klebsiella pneumoniae (Kp) producing CTX-M extended-spectrum ß-lactamase (ESBL) and/or carbapenemases (eg, KPC, VIM) from blood cultures (BCs) and the infectious disease (ID) consulting for timely appropriate antimicrobial therapy. Methods: This observational, retrospective study included adult patients with a first episode of Ec or Kp bloodstream infection (BSI) in a large Italian university hospital, where an inpatient ID consultation team (IDCT) has been operational. Results from the BCs tested for detecting bla CTX-M, bla KPC, bla NDM, bla OXA-48-like, and bla VIM genes by the eazyplex® SuperBug CRE assay in Ec and Kp organisms had been notified for antimicrobial therapy consulting. Results: In 321 BSI episodes studied, we found that 151 (47.0%) of Ec or Kp organisms harbored bla CTX-M and/or bla KPC and/or bla VIM (meantime from BC collection: 18.5 h). Empirical antimicrobial treatment was appropriate in 21.8% (33/151) of BSIs, namely 5.9% (3/51) of BSIs caused by KPC/VIM producers and 30.0% (30/100) of BSIs caused by CTX-M producers. After notification of results, the IDCT modified antimicrobial therapy (mean time from BC collection: 20 h) such that the proportion of appropriate treatments increased to 84.8% (128/151) of BSIs, namely 70.6% (36/51) of BSIs caused by KPC/VIM producers and 92.0% (92/100) of BSIs caused by CTX-M producers. Conclusion: Our study shows that a rapid diagnostic-driven clinical strategy allowed for early prescription of potentially effective antimicrobial therapy in BSIs caused by CTX-M ESBL- and/or KPC/VIM carbapenemase-producing Ec and Kp organisms.

Performance evaluation of the (1,3)-ß-D-glucan detection assay in non-intensive care unit adult patients.

OBJECTIVES: To assess the performance of the (1,3)-ß-D-glucan (BDG) detection assay in a large cohort of patients with suspected candidemia who were admitted to non-intensive care unit hospital wards. METHODS: This observational, retrospective cohort study was conducted in a 1,100-bed university hospital in Rome, where an infectious disease consultation team has been operational. Two groups of patients were included in the analysis: Group 1, patients with Candida bloodstream infection (BSI) who had at least one BDG test performed ±48 hours from the first positive blood culture (Candida BSI Group) and Group 2, patients with risk factors for candidemia who had at least one BDG test but had negative blood cultures (Control Group). Both Group 1 and Group 2 did not receive prior antifungal therapy. Different BDG cutoff values were considered: 80, 200, 300, 400, and ≥500 pg/mL. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve were calculated. RESULTS: A total of 1,296 patients were studied. Of them, 100 patients (candidemic) were in Group 1 and the remaining 1,196 patients (controls) were in Group 2. There were no differences in demographic characteristics between patients of the two groups. According to the above cutoff values, sensitivity (%) and specificity (%) of the BDG assay ranged from 91 to 60.7 and 87.7 to 97.8, respectively, whereas the PPV (%) and NPV (%) ranged from 38.2 to 68.3 and 99.1 to 97.0, respectively. CONCLUSION: Serum BDG has a very high NPV in a population with10% prevalence of candidemia. This NPV may support decisions to discontinue antifungal therapy in those patients who were empirically treated because of the suspect of candidemia.

Systematic clinical management of patients with candidemia improves survival.

OBJECTIVES: Taking into account the significant morbidity, mortality, and hospital costs related to Candidemia, our objective is to define if improving appropriateness in candidemia management was associated with better clinical outcomes. METHODS: A prospective observational monocentric cohort study was conducted. Adherence to five main elements was examined: appropriate selection of initial therapy; follow-up blood culture; echocardiography; ophthalmological examination; and removal of a central venous catheter. The correlation between the number of appropriate elements achieved and 30 day survival was examined. RESULTS: Patients with candidemia (n = 213) were enrolled. Adherence to all five elements was achieved in 36 cases (16.9%), while the majority adhered to three or four elements (28.2% and 37.1%, respectively). Multivariable Cox regression analysis revealed that the number of elements achieved was associated with survival [HR: 0.39 (0.30-0.52); p < 0.001]. Also, the number of elements achieved correlated positively with duration of therapy (p = 0.01), but not length of hospital stay (p = 0.56). CONCLUSIONS: Five elements, including therapeutic and non-therapeutic-related aspects, of care were good indicators of appropriate management of patients with candidemia. Implementation of evidence-based practice regarding optimal clinical management is crucial for any antimicrobial stewardship program.

Fecal calprotectin in management of Clostridium difficile infection: a longitudinal study.

BACKGROUND: Clostridium difficile infection (CDI) is characterized by a relevant intestinal neutrophil infiltrate. So far, role of fecal calprotectin in CDI, has been investigated only in few studies, mainly focused on diagnosis of the disease. AIM: By a longitudinal design, we assess fecal calprotectin concentrations (FCCs) in subjects with CDI, evaluating the correlation between fecal marker and response to therapy. METHODS: Clinical (diarrhea scoring) and laboratory (FCCs and leucocytes count) evaluation was performed in 56 subjects with CDI at time of diagnosis (T0) and after a week from starting of therapy (T1). Clinical response to therapy at T1 was related with both T0 and T1 FCC values. FCCs were also related to all-cause 30-day mortality, recurrence and death, both of them within 90 days. RESULTS: FCCs at T1 were significantly increased in subjects with persistence of diarrhea in respect to the other ones (285.5 ± 270 µg/g vs 150.7 ± 147 µg/g, respectively; p < .05). Patients who did not respond to therapy showed higher, but not significative, FCCs at T0 than patients who responded. No correlation was found among FCCs, both at T0 and T1, and the other outcomes. CONCLUSIONS: Longitudinal evaluation of FCCs in patients with CDI could support physicians in clinical management of disease, for example in term of duration (10 vs 14 days) or type (first vs second line therapy). Further and larger studies could confirm the eventual role of this marker in prognostic algorithms, mainly in prediction of recurrence.

Trimethoprim-sulfamethoxazole therapy for patients with carbapenemase-producing Klebsiella pneumoniae infections: retrospective single-center case series.

OBJECTIVE: The objective of the study was to evaluate the efficacy and tolerability of trimethoprim-sulfamethoxazole (also known as co-trimoxazole, TMPS) to treat Klebsiella pneumoniae (Kp)-K. pneumoniae carbapenemase (KPC) infections. METHODS: Clinical data of patients with a TMPS-susceptible Kp-KPC infection were collected as a case series. RESULTS: We report clinical outcomes and tolerability for 14 patients infected by Kp-KPC strains susceptible to TMPS, including three bloodstream infections. In ten cases (71.4%), TMPS was administered as monotherapy. In all but one case, Kp-KPC infection was cured. In the remaining patient, therapy was discontinued because of an adverse event. CONCLUSIONS: The use of TMPS to treat TMPS-susceptible Kp-KPC infections seems promising.

Resource-saving advice from an infectious diseases specialist team in a large university hospital: an exportable model?

AIM: To assess epidemiological features of patients for which a consultation by the infectious diseases consultation team was required, and the rate of clinical advice that led to resource-saving advice (R-SA): discontinuation of inappropriate therapy or prophylaxis, de-escalation and switch from parenteral to oral therapy. MATERIALS & METHODS: An infectious diseases consultation team was implemented in a 1100-bed university hospital in Italy. RESULTS: The most frequent infections for which an infectious diseases consultancy was required were pneumonia, bloodstream infections (17% by Candida) and urinary tract infections. In 828 patients (41.4%), interventions with the possibility of R-SA were suggested. CONCLUSION: Resource-saving advices were possible in 41% of cases. Recent surgery, having a central venous catheter, bloodstream, abdominal, surgical site or bone and joint infections were correlated to a higher probability of receiving R-SA.