A multisite evaluation of antifungal use in critical care: implications for antifungal stewardship.

Background: ICUs are settings of high antifungal consumption. There are few data on prescribing practices in ICUs to guide antifungal stewardship implementation in this setting. Methods: An antifungal therapy (AFT) service evaluation (15 May-19 November 2019) across ICUs at three London hospitals, evaluating consumption, prescribing rationale, post-prescription review, de-escalation and final invasive fungal infection (IFI) diagnostic classification. Results: Overall, 6.4% of ICU admissions (305/4781) received AFT, accounting for 11.41 days of therapy/100 occupied bed days (DOT/100 OBD). The dominant prescribing mode was empirical (41% of consumption), followed by targeted (22%), prophylaxis (18%), pre-emptive (12%) and non-invasive (7%). Echinocandins were the most commonly prescribed drug class (4.59 DOT/100 OBD). In total, 217 patients received AFT for suspected or confirmed IFI; 12%, 10% and 23% were classified as possible, probable or proven IFI, respectively. Hence, in 55%, IFI was unlikely. Proven IFI (n = 50) was mostly invasive candidiasis (92%), of which 48% had been initiated on AFT empirically before yeast identification. Where on-site (1 → 3)-ß-d-glucan (BDG) testing was available (1 day turnaround), in those with suspected but unproven invasive candidiasis, median (IQR) AFT duration was 10 (7-15) days with a positive BDG (≥80 pg/mL) versus 8 (5-9) days with a negative BDG (<80 pg/mL). Post-prescription review occurred in 79% of prescribing episodes (median time to review 1 [0-3] day). Where suspected IFI was not confirmed, 38% episodes were stopped and 4% de-escalated within 5 days. Conclusions: Achieving a better balance between promptly treating IFI patients and avoiding inappropriate antifungal prescribing in the ICU requires timely post-prescription review by specialist multidisciplinary teams and improved, evidence-based-risk prescribing strategies incorporating rapid diagnostics to guide AFT start and stop decisions.

Invasive candidiasis in critical care: challenges and future directions.

Invasive candidiasis is the most common critical care-associated fungal infection with a crude mortality of ~ 40-55%. Important factors contributing to risk of invasive candidiasis in ICU include use of broad-spectrum antimicrobials, immunosuppressive drugs, and total parenteral nutrition alongside iatrogenic interventions which breach natural barriers to infection [vascular catheters, renal replacement therapy, extracorporeal membrane oxygenation (ECMO), surgery]. This review discusses three key challenges in this field. The first is the shift in Candida epidemiology across the globe to more resistant non-albicans species, in particular, the emergence of multi-resistant Candida glabrata and Candida auris, which pose significant treatment and infection control challenges in critical care. The second challenge lies in the timely and appropriate initiation and discontinuation of antifungal therapy. Early antifungal strategies (prophylaxis, empirical and pre-emptive) using tools such as the Candida colonisation index, clinical prediction rules and fungal non-culture-based tests have been developed: we review the evidence on implementation of these tools in critical care to aid clinical decision-making around the prescribing and cessation of antifungal therapy. The third challenge is selection of the most appropriate antifungal to use in critical care patients. While guidelines exist to aid choice, this heterogenous and complex patient group require a more tailored approach, particularly in cases of acute kidney injury, liver impairment and for patients supported by extracorporeal membrane oxygenation. We highlight key research priorities to overcome these challenges in the future.

Neurological, visual, and MRI brain scan findings in 87 South African patients with HIV-associated cryptococcal meningoencephalitis.

BACKGROUND: HIV-associated cryptococcal meningoencephalitis (CM) is a leading cause of adult meningitis in sub-Saharan Africa. Neuroradiological data is however limited to case reports and small case series from developed countries and/or immunocompetent patients. METHODS: Eighty seven patients aged ≥18 hospitalized with a first episode of CM had magnetic resonance (MRI) imaging during the first two weeks of admission. A subset of eleven patients had follow-up scans approximately one month from their initial MRI scan. All had prospectively-recorded detailed neurological and visual examinations. RESULTS: An abnormal finding on neurological examination was detected in 33 (39%) patients. 38 (48%) patients experienced some visual loss. Neuroradiological lesions presumed to be cryptococcosis-related, as defined by the presence of dilated Virchow Robin spaces, pseudocysts or cryptococcomas, enhancing nodules, hydrocephalus, meningitis, focal perilesional oedema and infarcts, were detected in 55 (63%) patients. MRI findings suggestive of a second diagnosis were found in 18 (21%) patients. Visual loss was associated with the presence of cryptococcal-related lesions (p = 0.02). Blindness was associated with raised intracranial pressure (ICP) (p = 0.02). Of eleven patients with paired scans, brain swelling was identified on the initial scan in only one patient. CONCLUSION: The majority of patients had MRI brain scan abnormalities presumed secondary to CM. Dilated Virchow Robin spaces were the commonest neuroradiological lesion. Visual loss was associated with the degree of cerebral involvement as reflected by the presence of MRI abnormalities. Blindness was associated with the presence of raised ICP. Initial generalised brain swelling does not appear to be common, but further studies with paired scans are needed.

Lymphatic abnormalities demonstrated by lymphoscintigraphy after lower limb cellulitis.

BACKGROUND: Cellulitis is a common cause for admission to hospital, and repeated episodes are thought to damage the lymphatic system. Lymphoedema is recognized as a condition predisposing to cellulitis but there are no data to suggest its prevalence among a population presenting to hospital with acute cellulitis. OBJECTIVES: To ascertain whether lymphatic abnormalities represent a common problem in patients with lower limb cellulitis. METHODS: Patients admitted with cellulitis of the lower limb were invited to undergo clinical examination and lymphoscintigraphy. RESULTS: Thirty patients agreed to participate in the study. Fifteen underwent lymphoscintigraphy. Thirteen had abnormal scans indicating impaired lymph drainage (seven patients had clinical lymphoedema). CONCLUSIONS: Lymphatic abnormalities represent an important but unrecognized problem in patients with leg cellulitis.

Lactic acidosis in Gabonese children with severe malaria is unrelated to dehydration.

BACKGROUND: Hyperlactatemia is an important and common complication of severe malaria. We investigated changes in fluid compartment volumes in patients with severe malaria and control patients with the use of bioimpedence analysis. METHODS: We estimated extracellular water and total body water volumes in a total of 180 children: 56 with severe malaria, 94 with moderate malaria, 24 with respiratory tract infection, and 6 with severe diarrhea. RESULTS: There was a mean (+/-SD) decrease in total body water volume of 17+/-24 mL/kg (or 3% of total body water volume) in patients with severe malaria. This compares with a mean (+/-SD) decrease in total body water volume of 33+/-28 mL/kg (or 6% of total body water volume) in patients with severe diarrhea. There was no increase in extracellular water volume in patients with severe malaria, suggesting no significant intravascular volume depletion in patients with severe malaria. There was no relationship between lactatemia and any changes in fluid compartment volumes. CONCLUSIONS: The changes in fluid volumes that were observed are unlikely to be of physiological significance in the pathophysiology of severe malaria.