Invasive fungal infection following venetoclax and posaconazole co-administration.

The co-administration of venetoclax, a BCL-2 inhibitor, with a mould-active azole, such a posaconazole, has potential to both prevent invasive fungal infection (IFI) and reduce the required treatment dose, and cost, of venetoclax. Posaconazole drug-level monitoring is critical to ensuring adequate mould prophylaxis. A retrospective audit of 99 patients at a tertiary cancer centre, with myeloid malignancies co-prescribed venetoclax and posaconazole between January 2018 and April 2022, was undertaken to evaluate the adequacy of posaconazole prescribing and the rate of breakthrough IFI. Seventy-six patients (77%) had at least one posaconazole level measured in the study period, with 37% requiring a dose adjustment based on steady-state trough levels. Breakthrough IFI occurred in 4% of patients, typically within 1 month of commencing anti-mould prophylaxis. Close monitoring of posaconazole levels in venetoclax-treated patients, particularly in the early, outpatient setting, is critical.

Antifungal stewardship: developments in the field.

PURPOSE OF REVIEW: To outline key drivers and components of antifungal stewardship (AFS) programmes, the evidence for specific interventions, and methods to assess performance of programmes. RECENT FINDINGS: Recent developments in antifungal resistance and breakthrough invasive fungal diseases have increased the urgency for effective AFS. In practice, however, few hospitals have dedicated AFS programmes. To date, AFS programmes have centred around the provision of expert bedside reviews and have reduced costs and consumption of antifungal agents. Incorporating tools such as fungal diagnostics and therapeutic drug monitoring into AFS programme models is recommended. However, the application and impact of these tools in this context have not been adequately assessed. The effectiveness of AFS programmes has been measured in multiple ways but a standardized method of evaluation remains elusive. Few studies have explored the impact of AFS interventions on patient outcomes. SUMMARY: The uptake of formal AFS programmes has been slow. New initiatives integrating AFS tools in programmes, and measuring the impacts on patient outcomes are required given such data are not readily available. A comprehensive approach to evaluate AFS programmes by correlating the quantity and quality of antifungal prescribing with impacts on patient outcomes is needed. Consensus definitions for core AFS metrics are required to benchmark performance and are essential to the resourcing and sustainability of these programmes.

Dapsone safety in hematology patients: Pathways to optimizing Pneumocystis jirovecii pneumonia prophylaxis in hematology malignancy and transplant recipients.

Dapsone may be used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis in hematology patients receiving immunosuppressive therapy or after hematopoietic stem cell transplant (HSCT) in the setting of trimethoprim-sulfamethoxazole (TMP-SMX) adverse drug reaction (ADR) history. Dapsone-induced hematological toxicities such as oxidative hemolysis may limit use in these patients and modern assessments of dapsone allergy cross-reactivity in non-HIV patients with a sulfonamide allergy are largely absent. The aim of this single-centre, retrospective study was to describe dapsone usage in hematology patients requiring PJP prophylaxis, including HSCT recipients, over a 12-month period in terms of indications, incidence of dapsone-attributed oxidative hemolysis, and immune cross-reactivity in those previously labeled with a sulfonamide allergy, as well as describing potential opportunities for first-line TMP-SMX PJP prophylaxis reintroduction. Of 24 patients meeting the study inclusion criteria, 12 (50%) were receiving dapsone PJP prophylaxis post-HSCT. No cases of breakthrough PJP infection were noted. Sixteen patients (67%) were initiated on dapsone to avoid the perceived risk of further myelosuppression with TMP-SMX and five patients (21%) because of prior delayed immune-mediated allergy to TMP-SMX. None experienced rash with dapsone therapy. Six patients (25%) were successfully rechallenged on TMP-SMX, including one patient with prior TMP-SMX-associated rash. Four (17%) patients had confirmed oxidative hemolysis, all resulting in dapsone cessation. Dapsone PJP prophylaxis in hematology patients was effective and safe, with nonlife threatening dapsone-related hemolysis noted in a small number. An absence of sulfonamide allergy cross-reactivity was noted, suggesting greater TMP-SMX rechallenges or desensitization could be considered in those receiving dapsone.

Primary antifungal prophylaxis in adult patients with acute lymphoblastic leukaemia: a multicentre audit.

OBJECTIVES: The primary objectives were to investigate the prescribing practices of primary antifungal prophylaxis (PAP) and incidence of invasive fungal disease (IFD) in adult patients with ALL receiving induction-consolidation chemotherapy. Secondary objectives were to determine risk factors for IFD and resource utilization associated with IFD. METHODS: A retrospective chart review of adult patients with ALL from commencement of induction until completion of consolidation chemotherapy was undertaken from January 2008 to June 2013 in four hospitals in Melbourne, Australia. IFD was classified according to the revised European Organisation for Research and Treatment of Cancer criteria. Cost analysis was performed from an Australian public hospital perspective. RESULTS: Ninety-eight patients were included in the audit; 83 (85%) received PAP. Most patients (49/83, 59%) switched between two different antifungal agents, predominantly between liposomal amphotericin B and an azole. Five proven/probable and six possible IFD cases were identified. Proven/probable IFD was most common in patients receiving the BFM95 chemotherapy protocol. The incidence of proven/probable IFD was significantly lower in patients receiving PAP compared with those who did not (2/78, 2.6% versus 3/14, 21.4%; P = 0.024). For every five patients receiving PAP, one proven/probable IFD case would be prevented. Proven/probable IFD was associated with an additional median cost of 121,520 Australian dollars (95% CI: 90,781-180,141 Australian dollars; P < 0.001) compared with patients without IFD. CONCLUSIONS: This is the first multicentre study evaluating PAP use in patients with ALL. With the caveats of interpretation of retrospective, non-randomized data, PAP was associated with a reduced IFD risk.

Outcomes of an electronic medical record (EMR)-driven intensive care unit (ICU)-antimicrobial stewardship (AMS) ward round: Assessing the "Five Moments of Antimicrobial Prescribing".

OBJECTIVE: The primary objective of this study was to examine the impact of an electronic medical record (EMR)-driven intensive care unit (ICU) antimicrobial stewardship (AMS) service on clinician compliance with face-to-face AMS recommendations. AMS recommendations were defined by an internally developed "5 Moments of Antimicrobial Prescribing" metric: (1) escalation, (2) de-escalation, (3) discontinuation, (4) switch, and (5) optimization. The secondary objectives included measuring the impact of this service on (1) antibiotic appropriateness, and (2) use of high-priority target antimicrobials. METHODS: A prospective review was undertaken of the implementation and compliance with a new ICU-AMS service that utilized EMR data coupled with face-to-face recommendations. Additional patient data were collected when an AMS recommendation was made. The impact of the ICU-AMS round on antimicrobial appropriateness was evaluated using point-prevalence survey data. RESULTS: For the 202 patients, 412 recommendations were made in accordance with the "5 Moments" metric. The most common recommendation made by the ICU-AMS team was moment 3 (discontinuation), which comprised 173 of 412 recommendations (42.0%), with an acceptance rate of 83.8% (145 of 173). Data collected for point-prevalence surveys showed an increase in prescribing appropriateness from 21 of 45 (46.7%) preintervention (October 2016) to 30 of 39 (76.9%) during the study period (September 2017). CONCLUSIONS: The integration of EMR with an ICU-AMS program allowed us to implement a new AMS service, which was associated with high clinician compliance with recommendations and improved antibiotic appropriateness. Our "5 Moments of Antimicrobial Prescribing" metric provides a framework for measuring AMS recommendation compliance.

Impact of unit-wide chlorhexidine bathing in intensive care on bloodstream infection and drug-resistant organism acquisition.

BACKGROUND: Chlorhexidine gluconate (CHG) bathing has been reported to decrease bloodstream infections and colonisation of multidrug-resistant organisms (MROs) in intensive care units (ICUs). However, its effectiveness in an Australian setting has not been assessed. OBJECTIVE: To test whether the introduction of ICU-wide CHG bathing in place of triclosan would affect rates of the primary outcome of central line-associated bloodstream infections (CLABSI), or the secondary outcomes of ICU-acquired positive blood cultures or other clinical specimens, and MRO colonisation including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). METHODS: We conducted a single-centre, sequential, before-and-after observational study. Patient microbiological and clinical data were compared in the 12 months before and after the introduction of CHG bathing in the ICU. RESULTS: A total of 4262 ICU admissions were studied, 2117 before and 2145 during the CHG-bathing period. There were no significant changes in the rates of CLABSI (from 1.69/1000 central venous catheter-days [95% CI, 0.68-3.48] to 1.33 [95% CI, 0.49-2.90]; P = 0.68), or ICU-acquired positive blood cultures (from 5.14/1000 patientdays [95% CI, 3.45-7.39] to 4.45 [95% CI, 3.00-6.36]; P = 0.58). However, we observed a lower incidence of MRSA acquisition during the CHG-bathing period (mean difference, -2.13 [95% CI, -3.65 to -0.60] per 1000 patient-days; P = 0.007). There was no difference in the rate of isolates involving other pathogens including VRE. CONCLUSIONS: In a tertiary Australian ICU, routine CHG bathing compared with triclosan did not affect the rates of ICU-acquired CLABSI or positive blood cultures. However, it significantly decreased the incidence of MRSA acquisition.