ABSTRACT Introduction Clostridioides difficile infection (CDI) remains a leading cause of healthcare-associated infectious diarrhea, with a major burden driven by recurrences and severe or even fulminant disease in vulnerable hosts. The therapeutic landscape has shifted toward fidaxomicin-based antibiotic regimens, and microbiota restoration strategies including standardized microbiota-based products. Areas covered Recent international guidelines, outcome studies and pivotal trials focused on difficult-to-treat phenotypes: refractory or fulminant CDI, multiply recurrent CDI, and CDI in high-risk populations (immunocompromised, inflammatory bowel disease, critical illness) were reviewed. A PubMed search was supplemented by hand-searching additional references, guideline and regulatory documents. Evidence is summarized for optimized antibiotic regimens, bezlotoxumab, conventional fecal microbiota transplantation (FMT), FDA-approved microbiota-based products, and salvage strategies including intracolonic therapy and surgery. Expert opinion Advanced CDI management is moving from repeated antibiotic cycling toward individualized recurrence prevention and microbiota restoration strategies. Implementation requires diagnostic stewardship, earlier recognition of recurrences, clear pathways for microbiota-based therapy access, and multidisciplinary care for fulminant infection. Over the next five years, standardized microbiota therapeutics and better risk tools should shift care toward earlier, more durable recurrence prevention.

ABSTRACT Introduction Mansonellosis, a filarial disease caused by Mansonella genus parasites, affects hundreds of millions globally and represents a growing public health challenge. Currently, there are no coordinated international mansonellosis management programs or guidelines, but there is a growing recognition that mansonellosis control interventions do need to be formulated. Areas Covered Between 1 January 2025 and 1 September 2025, the search-terms ‘Mansonellosis’ and ‘Mansonella’ were used to identify literature concerning macrofilaricidal and microfilaricidal chemotherapeutic treatment of mansonellosis in the PubMed and Web-of-Science databases. Identified literature revealed Mansonella ozzardi susceptibility and regional community-support levels make mass drug administration with ivermectin (MDAi) viable for mansonellosis control in the Americas. Macrofilaricidal test-and-treat programs were found to be more appealing for African mansonellosis control because of sub-optimal M. perstans and M. streptocerca microfilaricidal responses. Shortening treatment times could, however, make curative macrofilaricides the best option in Africa and the Americas. Expert Opinion The susceptibility of M. ozzardi to ivermectin and the growing appeal of MDAi for malaria control will present opportunities for synergistic malaria-mansonellosis control programs in the Americas. New short course curative macrofilaricides, which are in development for onchocerciasis and lymphatic filariasis, will likely be useful for mansonellosis treatment and will make the disease much easier to manage.

ABSTRACT Introduction There is currently no unified standard treatment for Mycobacterium marinum (M. marinum) infection, and its treatment faces clinical challenges, such as limited drug options and increasing drug resistance. Therefore, reviewing the progress in its treatment is of significant importance for guiding clinical practice. This article systematically reviews the advances in the treatment of M. marinum infection. Areas covered This study systematically reviewed relevant literature by searching four electronic databases, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wan Fang database, for publications up to 1 January 2026, and summarized the current treatment landscape of M. marinum infections, including oral antibacterial monotherapy and combination regimens, novel local treatments such as photodynamic therapy, and adjuvant therapies including hyperthermia, surgical interventions, and immunomodulation. Expert opinion M. marinum infection can involve the skin and deep tissues, and standardized diagnosis and treatment are pivotal for improving its prognosis. Optimizing antimicrobial regimens and applying novel local therapies hold considerable value, yet critical issues, such as the lack of treatment standards, persist. Future multicenter studies and precision treatment models are needed to establish a new paradigm of precise, diversified, and standardized clinical management.

ABSTRACT Introduction The delay in diagnosis and management of cerebral aspergillosis leads to high mortality. The major challenges include low recognition of the disease, long turnaround time, and low sensitivity of available diagnostic modalities, and absence of standardized molecular diagnosis. Management is also suboptimal due to lack of optimal surgical strategies, the emergence of antifungal resistance, and poor penetration of antifungal drugs into the brain parenchyma. This article emphasizes new modalities for early diagnosis and optimal management that may improve outcomes. Area covered We searched the PubMed and Embase databases (since 2015 till 31 March 2025) using the terms ‘cerebral aspergillosis,’ ‘diagnosis ca,’ ‘management ca,’ and ‘treatment ca.’ The search was augmented by reviewing the references of those articles. Expert opinion Early diagnosis may be achieved by high index of suspicion, neuroimaging, stereotactic brain biopsy, and the use of galactomannan in serum and cerebrospinal fluid. Whole-genome sequencing and detection of cell-free nucleic acid can improve diagnostic capabilities. Surgical debridement of infected tissue will reduce disease burden and allow enhanced antifungal drug penetration. Voriconazole, posaconazole, and isavuconazole are recommended as primary therapy and therapeutic drug monitoring guided higher doses of azoles may improve outcomes. Olorofim and fosmanogepix are promising agents for the future.

ABSTRACT Introduction Cranial neurosurgery involves high-risk procedures with major clinical and economic implications. Effective preventive measures against surgical site infections (SSIs) can reduce morbidity, mortality, and healthcare costs. This systematic review and meta-analysis evaluated the effectiveness of care bundles in preventing SSIs in cranial neurosurgery. Methods Following PRISMA guidelines, a systematic search identified controlled studies (2014–2024) evaluating SSI prevention bundles in cranial neurosurgery. Meta-regression was performed, and evidence certainty was assessed using GRADE. Results Of 3945 records, 14 studies met inclusion criteria. Bundles integrated pre-, intra-, and postoperative measures. Implementation significantly reduced SSI incidence (pooled odds ratio [OR] 0.34; 95% confidence interval [CI] 0.23–0.51; p < 0.01). The presence of antimicrobial prophylaxis within bundles was associated with lower SSI risk (OR 0.45; 95% CI 0.22–0.92; p = 0.031). Evidence certainty was rated low, mainly due to observational design, though risk of bias, imprecision, and inconsistency were minimal. Conclusion Standardized care bundles effectively prevent SSIs in cranial neurosurgery, particularly when antimicrobial prophylaxis is included. These findings support adopting multimodal, evidence-based strategies in perioperative infection prevention protocols. Registration The study protocol was registered with the Open Science Framework (OSF) Registries prior to the literature search and is available from: https://doi.org/10.17605/OSF.IO/UBZW7.

ABSTRACT Introduction Pseudomonas aeruginosa bloodstream infections (BSIs) complicated by sepsis or septic shock are associated with high mortality. Although combination antibiotic therapy may increase early antimicrobial coverage, its effect on survival remains uncertain. This systematic review evaluated the impact of appropriate empirical and definitive combination therapy compared with monotherapy on mortality in this population. Methods Following PRISMA guidelines, we systematically searched eight databases through 31 August 2025, for studies enrolling adults with sepsis or septic shock due to confirmed P. aeruginosa BSIs that compared combination therapy with monotherapy. Data on study characteristics, treatment phase, and mortality outcomes were extracted. Risk of bias was assessed using ROBINS-I, and certainty of evidence was evaluated with GRADE. Results Eight observational studies including 1201 patients met the inclusion criteria. No consistent survival benefit was observed with definitive combination therapy. Some studies assessing empirical therapy reported lower mortality in selected high-risk subgroups; however, results were characterized by substantial clinical heterogeneity. Adverse events were infrequently reported, and overall certainty of evidence was very low. Conclusions Current evidence does not support routine use of combination therapy over monotherapy. Empirical combination therapy may be considered in carefully selected high-risk patients, with prompt de-escalation once susceptibilities are known.

ABSTRACT Background This study systematically synthesized existing evidence to evaluate whether outpatient treatment with nirmatrelvir/ritonavir during the acute phase reduces the incidence of long COVID. Methods We conducted a systematic search of Europe PMC, Medline, Scopus, and the Cochrane Library from inception to 15 September 2025. Eligible studies compared COVID-19 outpatients prescribed nirmatrelvir/ritonavir during the acute phase with those who did not receive the drug. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Results Nineteen studies met inclusion criteria. Overall, nirmatrelvir/ritonavir use during acute infection was associated with a significant reduction in the likelihood of developing post-COVID-19 condition (OR 0.85; 95% CI: 0.80–0.91; p < 0.00001; I2 = 99%). Protective effects were consistently observed across multiple clinical domains, including cardiovascular (arrhythmia, ischemic disease, heart failure), pulmonary (dyspnea, COPD), thromboembolic (DVT, PE), neurological (stroke, cognitive impairment, headache), psychiatric (depression), gastrointestinal, metabolic (new-onset diabetes), renal (AKI), and general symptoms (malaise and fatigue). Conversely, no significant differences were noted for cough, asthma, dysautonomia, anxiety, PTSD, sleep disturbances, musculoskeletal pain, or olfactory/gustatory dysfunction. Conclusions Early outpatient treatment with nirmatrelvir/ritonavir may mitigate the risk of developing several domains of long COVID, though its benefits are not uniform across all symptom categories.