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The approach to multidrug-resistant (MDR) Gram-negative bacilli (GNB) infections has changed following the introduction of avibactam-based β-lactam/β-lactamase inhibitor combinations. Ceftazidime/avibactam has become a cornerstone for the treatment of infections caused by KPC-producing Enterobacterales, whereas the recent availability of aztreonam/avibactam has provided the first targeted option against metallo-β-lactamase (MBL)-producing Enterobacterales. At the same time, the emergence of KPC variants, the increasing dissemination of MBLs and the growing complexity of resistance mechanisms have made both empirical and targeted therapeutic decisions increasingly challenging. This narrative review summarizes the current evidence regarding the microbiological activity, clinical efficacy and optimal place in therapy of avibactam-based combinations. Ceftazidime/avibactam is a cornerstore for the treatment of KPC infections, and significantly modified the outcome of patients with KPC infections during the last decade. Robust observational studies demonstrated its clinical efficacy and safety. It may also represent a carbapenem-sparing option for treating infections due to difficult-to-treat ESBL- and OXA-48-producing Enterobacterales. Moreover, its activity against MDR Pseudomonas aeruginosa makes it an attractive option for empirical therapy in patients with risk factors for this non-fermenting GNB. Aztreonam/avibactam represents the first-line option for the treatment of MBL-producing Enterobacterales and plays a pivotal role in the current era of increasing dissemination of multiple carbapenemases. Their optimal clinical positioning should rely on optimal use in empirical therapy in patients with rectal colonization with carbapenem-resistant Enterobacterales who develop sepsis or septic shock, antimicrobial stewardship principles and integration of local epidemiology, microbiological data and patient characteristics to maximize efficacy while preserving their long-term activity.

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Antimicrobial resistance (AMR) represents a major global public health concern, rendering available antimicrobials ineffective and leading to infections that are difficult to treat. Artificial intelligence (AI) has been increasingly applied across the AMR continuum, including resistance prediction, rapid diagnostics, new antimicrobial discovery, drug repurposing, antimicrobial surveillance, and clinical decision support. In this review, we aim to highlight recent developments in the use of artificial intelligence (AI) to address antimicrobial resistance (AMR). In addition, we review computational methods that help interpret genomic, phenomic, clinical, and epidemiological data to support the development of treatment strategies and novel antimicrobial agents. The key issues addressed include data quality, model interpretability, external validation, regulatory requirements, privacy, and fairness. While AI is not a complete solution to AMR, it can certainly strengthen the global AMR response by complementing key areas of AMR such as antimicrobial stewardship, infection prevention, laboratory diagnostics, and global surveillance.

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Tick-borne encephalitis (TBE) is an emerging viral infection in Europe and Asia. Climate and environmental changes are expanding the distribution and activity of Ixodes ticks, increasing human exposure. Most infections are asymptomatic, but symptomatic cases may present with a biphasic illness that can progress to meningitis or encephalitis, sometimes leading to long-term neurological sequelae, particularly in the elderly population. Currently, treatment is limited to supportive care, as no specific antiviral therapy is available. Effective vaccines exist and represent the main preventive strategy, although coverage remains variable. This paper provides an overview of epidemiology, clinical features, and prevention of TBE.

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Introduction. Dengue Fever (DF), caused by the Dengue virus (DENV), represents a major and expanding global public health challenge. Vaccination is an important public health tool that could prevent Dengue infection and reduce symptoms, including severe Dengue. Several dengue vaccines have been studied and implemented in selected countries; however, evidence on their efficacy/effectiveness, safety, and optimal use varies across populations and settings, highlighting the need for a comprehensive evaluation. Methods. This systematic review and meta-analyses followed PRISMA guidelines. Literature from 2010 was searched across three databases. Independent reviewers screened and extracted data, resolving conflicts with expert input. Risk of bias was assessed using ROB2 and the Newcastle-Ottawa Scale. Random-effects meta-analyses were conducted, reporting pooled Relative Risk and vaccine efficacy, and Geometric Mean Ratios, when feasible. Results. Seventy-nine studies were included, evaluating Dengue vaccines in adults (46.8%), children/adolescents (31.6%), and mixed-age populations (20.3%). Chimeric Yellow Fever–Dengue Tetravalent Vaccine (CYD-TDV/Dengvaxia®) was assessed in 28 trials, 3 of which reported a pooled vaccine efficacy of 55% (95%CI 47%-62, I2 = 86.9%; p < 0.001) against Dengue. Vaccine-induced Geometric Mean Titers (GMTs) increased 5.5- to 12.4-fold across serotypes, with no significant increase in the control groups. When available, greater effectiveness was observed in baseline seropositive individuals and older children. Takeda-003 (TAK-003/QDENGA®) was evaluated in 23 trials, showing sustained efficacy against virologically confirmed dengue (43.5%–82.1%) and high protection against hospitalization (approximately 87%–90%). Phase I–II studies for the candidate vaccine TV003/TV005 demonstrated favourable safety and immunogenicity profiles during the available follow-up. Other promising candidates included other investigational vaccines such as subunit (V180) or DNA-based (TVDV, D1ME100). Overall, Dengue vaccines were generally well tolerated, with most adverse events being mild to moderate during follow-up. Discussion This review demonstrates substantial progress in Dengue vaccine development. Importantly, CYD-TDV favorable balance is limited to individuals with prior dengue exposure, whereas vaccination of seronegative individuals has been associated with an increased risk of severe dengue. Both CYD-TDV and TAK-003 showed robust immunogenicity and acceptable safety profiles. Emerging vaccine candidates, including TV003/TV005, Butantan-DV, TDEN, inactivated, subunit, and DNA-based platforms, have also shown promising safety and immunogenicity results in early-phase trials. Future attempts should focus on developing Dengue vaccines that provide safe, balanced, and durable protection against all four Dengue virus serotypes while minimizing the risk of antibody-dependent enhancement, focusing also on special populations.

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Background: The increasing prevalence of antimicrobial resistance (AMR) has created an urgent need for alternative therapeutic strategies. Acinetobacter baumannii, a major cause of hospital-acquired infections, has been classified by the World Health Organization as a critical priority pathogen due to its high levels of multidrug resistance. Bacteriophage therapy has re-emerged as a potential approach to combat infections caused by multidrug-resistant organisms. Methods: Fifty multidrug-resistant (MDR) A. baumannii clinical isolates were collected. Bacteriophages were isolated from hospital sewage using standard enrichment protocols and screened for lytic activity against these isolates using spot and plaque assays. Morphological characterization of purified phages was performed using transmission electron microscopy. Results: Three bacteriophages — vB_AbaS_SRNAIIMS002, vB_AbaS_SRNAIIMS008, and vB_AbaP_SRNAIIMS010 — were isolated and demonstrated lytic activity against MDR A. baumannii. Plaque assays revealed clear central zones with surrounding halos, indicating active bacterial lysis. Host range testing showed that two phages exhibited activity against multiple clinical isolates, whereas one displayed a narrow host range. Transmission electron microscopy revealed that two phages belonged to the family Siphoviridae, whereas one was morphologically consistent with the family Podoviridae. Conclusions: This study reports the isolation and characterization of three bacteriophages active against MDR A. baumannii. These findings highlight the feasibility of isolating lytic phages from environmental sources and support further investigation of bacteriophage therapy as a complementary strategy to address infections caused by multidrug-resistant pathogens.

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Background: Invasive pulmonary aspergillosis (IPA) is a serious infection in critically ill patients. Galactomannan detection in endotracheal aspirates (ETA) has emerged as a promising non-invasive diagnostic method. This study evaluates the supportive diagnostic value of ETA galactomannan in ICU patients suspected to have IPA. Methods: We conducted a prospective observational cohort study over two years, enrolling 120 patients in the medicine ICU at a tertiary care centre in India (January 2022 to October 2023). Patients aged over 14 years on mechanical ventilation for >48 hours meeting the entry criteria of the BM-AspICU algorithm were included. ETA galactomannan was measured and correlated with IPA classification. Results: Of 120 patients, 37% (n=44) had probable IPA and 63% (n=76) were classified as colonisers or possible IPA. The optimal ETA galactomannan cut-off was 1.097, yielding sensitivity 72.73% (95% CI 57.2–85.0%), specificity 84.2% (95% CI 74.4–90.7%), PLR 4.86, NLR 0.35, and AUC 0.844 Conclusions: ETA galactomannan supports IPA diagnosis with favourable sensitivity and specificity. However, given the limitations of clinical scoring-based reference standards and the potential plateau in colonizer reduction at higher cut-offs, it should be integrated into a comprehensive diagnostic approach incorporating clinical, radiological, and microbiological criteria.

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Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a World Health Organization critical-priority pathogen, but the contribution of blaOXA-23 and blaNDM co-carriage to resistance across antimicrobial classes is poorly defined in southern Vietnam. Objectives: To describe the carbapenemase gene profile and antimicrobial susceptibility of clinical A. baumannii isolates from a Vietnamese tertiary hospital, to estimate the association between carbapenemase genotypes and class-level resistance, and to assess the concordance between automated phenotypic carbapenemase prediction and multiplex PCR. Methods: Single-centre, laboratory-based cross-sectional study of 172 non-duplicate clinical A. baumannii isolates collected consecutively over 28 months. Susceptibility was determined on the BD Phoenix M50 system, except colistin, which was tested by reference broth microdilution, and interpreted according to CLSI M100 (2023). Denominators vary by agent and are reported explicitly. Class-level resistance was resistance to at least one tested agent in the class. Six carbapenemase genes were detected by multiplex PCR. Firth penalized logistic regression (reference genotype: blaOXA-51 only) was used to estimate genotype-resistance associations; concordance was assessed using Cohen’s κ, sensitivity, specificity and predictive values. Results: 158 of 172 isolates (91.9%) met the multidrug-resistance definition. blaOXA-51 (98.3%) and blaOXA-23 (83.7%) predominated; blaNDM was detected in 23.3%, and blaOXA-23/blaNDM co-carriage in 16.3% (28/172). Colistin resistance was detected in 3 of 156 evaluable isolates (1.9%). The blaOXA-51/blaOXA-23 genotype was associated with higher odds of resistance in all six classes examined (OR 7.60-18.59, all p ≤ 0.003). Additional carriage of blaNDM was associated with a further increase for carbapenems (OR 13.10, 95% CI 1.90-90.27), aminoglycosides (16.40, 2.39-112.40), fluoroquinolones (13.10, 1.90-90.27), penicillin/β-lactamase inhibitor combinations (15.31, 2.08-112.97) and trimethoprim/sulfamethoxazole (8.27, 1.36-50.26; all p ≤ 0.022), but not for extended-spectrum cephalosporins (19.00, 0.90-401.19, p = 0.058). The blaOXA-51/blaNDM genotype without blaOXA-23 was not significantly associated with resistance in any class. The BD Phoenix M50 predicted Ambler class D with moderate agreement (κ = 0.536) but assigned class B to only 1 of 40 blaNDM-positive isolates (κ = 0.038); all 38 isolates reported as carbapenemase detected, class not determined carried blaNDM. Conclusions: In this collection, blaOXA-23 was the genotype most consistently associated with resistance across multiple antimicrobial classes, and blaNDM was associated with resistance mainly when carried together with blaOXA-23. Automated phenotypic classification rarely assigned NDM-producing isolates to Ambler class B, although a carbapenemase result of undetermined class had a high positive predictive value for blaNDM. These single-centre findings are associative; molecular confirmation and clonality analysis are warranted in comparable settings.

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Helicobacter cinaedi is an emerging Gram-negative pathogen, possibly involved in the pathogenesis of atherosclerosis and increasingly recognized as a cause of bacteraemia, cellulitis and vascular infections, particularly in immunocompromised and elderly patients. Infection of vascular grafts by H. cinaedi remains exceedingly rare. We report a case of H. cinaedi infection involving an aortic aneurysm and an aorto-bi-iliac endoprosthesis in an immunocompetent patient, highlighting the diagnostic challenges posed by culture-negative infections and the crucial role of Next-Generation Sequencing (NGS) in pathogen identification and therapeutic management.

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Introduction: Vascular prosthetic infections (VPI) are associated with high morbidity and mortality, often requiring prolonged antimicrobial therapy. The emergence of carbapenem-resistant Enterobacterales (CRE) represents a significant challenge due to the limited availability of outpatient treatment options. While ceftazidime-avibactam is a cornerstone of the treatment of CRE infections, its 12-hour stability limit poses a barrier for standard Outpatient Parenteral Antimicrobial Therapy (OPAT). Case presentation: We describe a 78-year-old male with multiple comorbidities (diabetes, peripheral artery disease, and ischemic cardiomyopathy) who presented with a VPI following an axillo-femoral bypass. Initial cultures isolated MRSA and ESBL-producing Klebsiella pneumoniae. Despite surgical debridement and various antibiotic regimens, the patient experienced a recurrence with inguinal fistulization. A subsequent isolate of K. pneumoniae demonstrated resistance to both ertapenem and ceftolozane-tazobactam. Treatment was transitioned to daptomycin (500 mg daily) and ceftazidime-avibactam (2.5 g three times a day), with oral rifampin added for anti-biofilm activity. To facilitate early discharge per the patient's request, ceftazidime-avibactam was administered off-label via an elastomeric pump. A continuous infusion regimen of 5 g every 12 hours was delivered through a PICC line. This schedule addressed the drug’s stability constraints while requiring only two daily administrative interventions. The patient completed the OPAT course without adverse events or signs of pyridine-related toxicity. Clinical and microbiological resolution was achieved, and no relapses were detected during the follow-up period. Conclusions: This case demonstrates that continuous 12-hour infusion of ceftazidime-avibactam via elastomeric pumps is a feasible and safe strategy for managing complex CRE infections in the OPAT setting. Such tailored approaches can enhance patient quality of life and reduce hospital stays, though further prospective studies are needed.

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Campylobacter jejuni is a common cause of bacterial gastroenteritis, while cardiac involvement is a rare extraintestinal complication. We report the case of a 21-year-old immunocompetent man who developed acute perimyocarditis three days after microbiologically confirmed C. jejuni enteritis. He presented with pleuritic chest pain, elevated inflammatory markers, and increased high-sensitivity troponin I levels. Echocardiography showed preserved ventricular function, whereas cardiac magnetic resonance imaging (CMR) demonstrated myocardial edema and subepicardial-to-mid-myocardial late gadolinium enhancement, fulfilling the Revised Lake Louise Criteria for acute myocarditis. The patient had an uncomplicated clinical course and was discharged in stable condition. This case highlights the importance of considering perimyocarditis in young patients presenting with chest pain following recent gastroenteritis and underscores the diagnostic value of CMR.

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Knowledge regarding parasites and the diseases they cause remains limited in the pre-microscopic era. Historical medical records concerning cutaneous parasitic infections often lack precision, leaving our understanding of these conditions in earlier centuries largely speculative. While the history of intestinal parasites is well-documented back to antiquity, literature on cutaneous parasites and filariasis primarily dates only to the late 18th century. However, Cerrahiyetü'l Haniyye - the first illustrated surgical textbook written in 15th century Anatolia - presents these conditions in a manner strikingly consistent with modern clinical understanding. This seminal work offers a definitive, early account of cutaneous parasites, accompanied by detailed clinical descriptions that require no interpretation. Furthermore, the unique arrangement of miniature illustrations depicting surgical procedures performed to treat skin parasites makes an extremely important contribution to the known history of skin parasites.

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