In immunocompromised patients, pneumonia presents a diagnostic challenge due to diverse etiologies, nonspecific symptoms, overlapping radiological presentation, frequent co-infections, and the potential for rapid progression to severe disease. Thus, timely and accurate diagnosis of all pathogens is crucial. This narrative review explores the latest advancements in microbiological diagnostic techniques for pneumonia in immunocompromised patients. It covers major available microbiological tools for diagnosing both community-acquired and hospital-acquired pneumonia, encompassing a wide spectrum of pathogens including bacterial, viral, fungal, and parasitic. While traditional culture methods remain pivotal in identifying many pneumonia-causing etiologies, their limitations in sensitivity and time to results have led to the rise of non-invasive antigen tests and molecular diagnostics. These are increasingly employed alongside cultures and microscopy for more efficient diagnosis, mainly in viral and fungal infections. Lastly, we report the future of pneumonia diagnostics, exploring the potential of metagenomics and CRISPR/Cas13a for more precise and rapid pathogen detection in immunocompromised populations.

To explore persistent candidemia by different Candida spp. Observational, retrospective, multicenter study including patients with candidemia (Jan 2018-Dec 2022) from 3 hospitals in Italy and Spain. The primary outcome was persistent candidemia, defined as positive blood culture (BC) yielding the same Candida spp≥5 days from the start of active antifungals. Patients with no available follow-up BCs were excluded. A competing risk analysis (competing risk of death) was performed using Fine and Gray regression models. Among 1188 patients, 298 (25.1%) had persistent candidemia. Cancer (sHR 1.335, 95% CI 1.037-1.633, p=0.011), total parenteral nutrition (sHR 1.440, 95%CI 1.062-1.818, p=0.006), Candida parapsilosis (sHR 1.312, 95% CI 1.075-1.633, p=0.03) and Candida auris (sHR 1.549, 95% CI 1.155-2.159, p=0.029) compared to Candida albicans, were associated with increased risk of persistent candidemia, whereas primary candidemia (sHR 0.573, 95% CI 0.321-0.825, p<0.001) and early source control (sHR 0.557, 95% CI 0.401-0.713, p<0.001) were protective. Persistent candidemia was associated with higher 30-day mortality (aHR 1.605, 95% CI 1.176-2.191, p=0.003). Persistent candidemia affects one in four patients with Candida BSI. Infections caused by Candida parapsilosis or Candida auris require individualized management, with early source control being essential to reduce the risk of persistence.

Amoebic liver abscess is a severe and potentially life-threatening infection requiring prompt diagnosis and early targeted treatment. Diagnosis is challenging because conventional diagnostic methods such as light microscopy and serology are often unreliable. Molecular techniques have emerged as an additional diagnostic tool, suddenly becoming the new diagnostic reference standard. More recently, commercial multiplex PCR panels, including FilmArray, have been introduced, which permit the simultaneous detection of several enteric pathogens including Entamoeba histolytica in stool samples. We report a case of an amoebic liver abscess promptly diagnosed by FilmArray gastrointestinal panel performed on liver drainage fluid.

West Nile virus (WNV) is among the most widespread arboviruses and has become a seasonal threat in temperate regions. Sustained in an enzootic bird-mosquito cycle, with humans and horses as incidental hosts, its geographic range has expanded in recent decades due to ongoing climatic and ecological changes. While most infections are asymptomatic or mild, a minority progress to neuroinvasive disease with high morbidity and long-term sequelae. This review summarizes current knowledge on epidemiology, pathogenesis, clinical spectrum, diagnostic challenges, therapeutic options, prevention, and research gaps. Lineages 1 and 2 co-circulate in Europe, where repeated large outbreaks highlight WNV adaptability to warmer summers, altered rainfall, and expanded mosquito habitats driven by recent ecological shifts. After inoculation, replication occurs in keratinocytes and dendritic cells, amplification in lymph nodes, and dissemination to visceral organs and the central nervous system. Neuroinvasion depends on viral proteins and host immune responses. Severe disease is associated with advanced age, immunosuppression, comorbidities, and genetic susceptibility. Clinical manifestations range from febrile illness to meningitis, encephalitis, or acute flaccid myelitis. Persistent neurological and functional sequelae are common, adding to disease burden. Diagnosis relies on molecular and serological tests, limited by short viremia and cross-reactivity with other flaviviruses. No approved antiviral therapy exists; management is supportive. Experimental antivirals, monoclonal antibodies, and interferon have shown mixed results. Vaccine candidates have progressed to phase 1-2 trials, but none are licensed for humans. Prevention relies on integrated vector control, veterinary surveillance, and donor screening, framed within a One Health approach. WNV exemplifies the impact of global ecological change on zoonotic diseases. Strengthening surveillance, refining diagnostics, and advancing antivirals and vaccines through multidisciplinary collaboration are essential to mitigate future outbreaks.

Purpose of Review: In this narrative review, we discuss recent literature regarding early antifungal therapy in critically ill patients, focusing in particular on the current role of empirical antifungal treatment. Recent Findings: While the direction of effect in randomized controlled trials (RCTs) exploring efficacy of empirical therapy in intensive care unit (ICU) patients with suspected invasive candidiasis (IC) was most frequently toward a favorable impact of empirical therapy, no formal demonstration of superiority was observed. Summary: Main results from RCTs seem in contrast with the increased mortality reported from observational studies in case of delayed antifungal therapy in patients with IC, suggesting, in our opinion, that further research is still necessary to better delineate the precise subgroup of ICU patients with suspected IC who may benefit from early antifungal therapy, either early empirical based on risk scores or diagnostic-driven, or a combination of both.

Background: Pneumocytis jirovecii pneumonia (PJP) has high mortality rates in immunocompromised children, even though routine prophylaxis has decreased in incidence. The aim of this case series is to present the radiological and clinical pathway of PJP in a pediatric population. Description of Cases: All PJP cases in non-HIV/AIDS patients diagnosed at Istituto Giannina Gaslini Pediatric Hospital in Genoa (Italy) from January 2012 until October 2022 were retrospectively evaluated. Nine cases were identified (median age: 8.3 years), and of these, 6/9 underwent prophylaxis with trimethoprim/sulfamethoxazole (TMP/SMX; five once-a-week schedules and one three times-a-week schedule), while 3/9 did not receive this. PJP was diagnosed by real-time PCR for P. jirovecii-DNA in respiratory specimens in 7/9 cases and two consecutive positive detections of β-d-glucan (BDG) in the serum in 2/9 cases. Most patients (6/8) had a CT scan with features suggestive of PJP, while one patient did not undergo a scan. All patients were treated with TMP/SMX after a median time from symptoms onset of 3 days. In 7/9 cases, empirical TMP/SMX treatment was initiated after clinical suspicion and radiological evidence and later confirmed by microbiological data. Clinical improvement with the resolution of respiratory failure and 30-day survival included 100% of the study population. Discussion: Due to the difficulty in obtaining biopsy specimens, PJP diagnosis is usually considered probable in most cases. Moreover, the severity of the clinical presentation often leads physicians to start TMP/SMX treatment empirically. BDG proved to be a useful tool for diagnosis, and CT showed good accuracy in identifying typical patterns. In our center, single-day/week prophylaxis was ineffective in high-risk patients; the three-day/week schedule would, therefore, seem preferable and, in any case, should be started promptly in all patients who have an indication of pneumonia.