Fusarium species are filamentous fungi widely encountered in nature, and may cause invasive disease in patients with hematologic conditions. Patients at higher risk are those with acute leukemia receiving induction remission chemotherapy or allogeneic hematopoietic cell transplant recipients. In these hosts, invasive fusariosis presents typically with disseminated disease, fever, metastatic skin lesions, pneumonia, and positive blood cultures. The prognosis is poor and the outcome is largely dependent on the immune status of the host, with virtually a 100% death rate in persistently neutropenic patients, despite monotherapy or combination antifungal therapy. In this paper, we will review the epidemiology, clinical manifestations, diagnosis, and management of invasive fusariosis affecting patients with hematologic diseases.

Background: The use of quinolone prophylaxis in high-risk neutropenic patients is considered standard of care but the development of resistance is a concern. Previous studies have focused mainly on quinolone resistance among patients receiving prophylaxis, with very few data reporting its impact on the hospital microbial epidemiology. Methods: We analyzed a cohort of 329 episodes of chemotherapy-induced neutropenia in adults, and compared two periods: 2005 (period 1, no prophylaxis, n=110) and 2006-2008 (period 2, ciprofloxacin prophylaxis, n=219). Outcomes analyzed were the frequency of febrile neutropenia, bacteremia, duration of antibiotic therapy and hospitalization, and antimicrobial resistance to ciprofloxacin and extended-spectrum beta-lactamase [ESBL] production. We analyzed resistance rates (by patients-day) in the cohort, as well as in other patients (neutropenic and non-neutropenic, 11,975 patients-day) admitted to the hematology unit in the same period, taking into consideration the general resistance patterns in the hospital. Results: Quinolone prophylaxis (period 2) resulted in fewer episodes of febrile neutropenia (159/219 [73%] vs. 102/110 [93%], Chi-square 18.09, p = 0.00002), and bacteremia (49/219 [22] vs. 36/110 [33%], Chi-square 4.10, p = 0.04), shorter duration of antibiotic therapy (p = 0.0002) and hospitalization (p = 0.002), but more frequent use of carbapenems (79/219 [36%] vs. 15/110 [14%], Chi-square 18.06, p = 0.0002). In addition, period 2 was associated with higher rates of quinolone resistance (6.77 vs. 3.02 per 1,000 patients-day, p = 0.03). The rate of ESBL-producing enterobacteria in the two periods was slightly higher in patients receiving quinolone prophylaxis (1.27 vs. 0.38 per 1,000 patients-day, p = 0.26) as well as in the hematology unit overall (1.59 vs. 0.53 per 1,000 patients-day, p = 0.08), but remained stable in the whole hospital (0.53 vs. 0.56 per 1,000 patients-day, p = 0.74). Conclusions: Ciprofloxacin prophylaxis was beneficial in high risk neutropenic patients, but important modifications in the prescription of carbapenems and on antimicrobial resistance patterns of isolates were observed. The importance of hospital or ward ecology must be taken into account when deciding for quinolone prophylaxis in high-risk neutropenic patients.

The COVID-19 pandemic caused >6 million deaths worldwide, often from respiratory failure. Complications frequently occurred in hospitalized patients, particularly in the intensive care unit. Among these, fungal infections were a cause of high morbidity and mortality. Invasive aspergillosis, candidiasis and mucormycosis were the most serious of these infections. Risk factors included alterations in immune defense mechanisms by COVID-19 itself, as well as immunosuppression due to various therapies utilized in severely ill patients. Diagnosis was often challenging due to lack of sensitivity of current testing. Outcomes were generally poor, due to significant co-morbidities and delayed diagnosis, with mortality rates >50% in some studies. High index of clinical suspicion is needed to facilitate early diagnosis and initiation of appropriate antifungal therapy.

Introduction: Staphylococcal colonization is a risk factor for healthcare-associated infections, which are frequent in Neonatal Intensive Care Units (NICU). This study analyzed microbiology, epidemiology and clinical aspects of Staphylococcus spp. colonizing neonates. Methodology: Nasal or periumbilical swabs were evaluated from 175 newborns admitted to a NICU of a Rio de Janeiro hospital from March to September 2009. Clinical data were obtained from the medical records. SCCmec typing and the mecA and Panton-Valentine Leukocidin (PVL) genes were detected by PCR. Clonal diversity was evaluated by pulsed-field gel electrophoresis. Results: Staphylococcus spp. isolates were detected in 98 (56%) neonates, 66.3% of them had birth weight ≤ 2500 g, 62.2% were preterm (˂ 37 weeks) and the mean length of hospitalization was 14.9 days. Among the 133 isolates identified, 48.1% were S. epidermidis, 23.3% S. haemolyticus and 13.5% S. aureus. Methicillin-resistant Staphylococcus isolate was detected in 77.6% of neonates. The methicillin-resistant S. aureus isolates carried the SCCmec type IV, while 94.6% of S. epidermidis and 85.7% of S. haemolyticus presented non-typeable cassettes. Among the S. aureus, 55.6% had PVL genes and the USA800 genotype was prevalent. Two genotypes of S. epidermidis and one of S. haemolyticus clustered 42.2% and 25.8% of the isolates, respectively. S haemolyticus colonization was associated with the use of parenteral nutrition and mechanical ventilation. Conclusion: High rate of neonates colonized by methicillin-resistant Staphylococcus species and the permanence of clones circulating in the NICU highlight the importance for continuous and preventive surveillance in this high-risk population.

Background: Staphylococcus aureusis one of the major causes of bloodstream infections (BSI) worldwide, representing a major challenge for public health due to its resistance profile. Higher vancomycin minimum inhibitory concentrations (MIC) inS. aureusare associated with treatment failure and defining optimal empiric options for BSIs in settings where these isolates are prevalent is rather challenging. In silico pharmacodynamic models based on stochastic simulations (Monte Carlo) are important tools to estimate best antimicrobial regimens in different scenarios. We aimed to compare the pharmacodynamic profiles of different antimicrobials regimens for the treatment ofS. aureusBSI in an environment with high vancomycin MIC.Methods: Steady-state drug area under the curve ratio to MIC (AUC/MIC) or the percent time above MIC (fT > MIC) were modeled using a 5000-patient Monte Carlo simulation to achieve pharmacodynamic exposures against 110 consecutiveS. aureusisolates associated with BSI.Results: Cumulative fractions of response (CFRs) against allS. aureusisolates were 98% for ceftaroline; 79% and 92% for daptomycin 6 mg/kg q24h and for the high dose of 10 mg/kg q24h, respectively; 77% for linezolid 600 mg q12h when MIC was read according to CLSI M100-S26 instructions, and 64% when MIC was considered at the total growth inhibition; 65% and 86% for teicoplanin, three loading doses of 400 mg q12 h followed by 400 mg q24 h and for teicoplanin 400 mg q12 h, respectively; 61% and 76% for vancomycin 1000 mg q12 h and q8 h, respectively.Conclusions: Based on this model, ceftaroline and high-dose daptomycin regimens delivered best pharmacodynamic exposures againstS. aureusBSIs. Teicoplanin higher dose regimen achieved the best CFR (86%) among glycopeptides, although optimal threshold was not achieved, and vancomycin performance was critically affected by theS. aureusvancomycin MIC ≥2 mg/L. Linezolid effectiveness (CFR of 73%) is also affected by high prevalence of isolates with linezolid MIC ≥2 mg/L. These data show the need to continually evaluate the pharmacodynamic profiles of antimicrobials for empiric treatment of these infections.