Germs

11 pages, 889 KB

Open AccessReview

A National Multidisciplinary Consensus to Develop an HIV Pre-Exposure Prophylaxis (PrEP) Referral Framework in Romania

by Oana Săndulescu, Anca Streinu-Cercel, Cătălina Poiană, Viorel Jinga, Beatrice Mahler, Gheorghe Gindrovel Dumitra, Sandra Adalgiza Alexiu, Simona Negreș, Cristina-Elena Zbârcea, George-Sorin Țiplică, Mihai Mitran, Robert Stoica, Mariana Mărdărescu, Șerban Benea, Adrian Gabriel Marinescu, Victor Daniel Miron, Elena Mătăsaru, Odette Chirilă, Sorin Petrea, Iulian Petre, Mihai Lixandru and Adrian Streinu-Cercel Show full author list Hide full author list

Germs 2026, 16(1), 8; https://doi.org/10.3390/germs16010008 - 17 Mar 2026

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Abstract

Background: Despite major advances in antiretroviral therapy, HIV transmission remains an important public health challenge. Pre-exposure prophylaxis (PrEP) is a highly effective prevention strategy, offering a significant opportunity to further reduce new HIV infections through expanded access and optimized implementation. Methods: [...] Read more.

Background: Despite major advances in antiretroviral therapy, HIV transmission remains an important public health challenge. Pre-exposure prophylaxis (PrEP) is a highly effective prevention strategy, offering a significant opportunity to further reduce new HIV infections through expanded access and optimized implementation. Methods: A national multidisciplinary consensus process was conducted to define principles and operational pathways for PrEP referral and linkage in Romania. Experts from different medical fields, professional societies, academic institutions, and community-based organizations participated in structured discussions. Results: The consensus highlighted relevant knowledge gaps related to HIV prevention and PrEP among specialists working outside the field of infectious diseases, including difficulty recognizing risk factors for HIV, uncertainty about next steps after identifying risk factors, and uneasiness discussing sexual health. The consensus also emphasized a shared commitment of these professional societies to address these gaps through pragmatic, specialty-adapted training. Key priorities included improved HIV risk recognition in routine care, development of communication skills, and clear referral pathways to PrEP services. Existing barriers were also discussed, underscoring the importance of multidisciplinary networks and community engagement. Conclusions: This consensus provides a structured, context-adapted framework to support the upcoming nationwide implementation of PrEP in Romania. By strengthening provider education, clarifying clinical pathways, and fostering interdisciplinary collaboration, it offers a foundation for equitable and sustainable HIV prevention. Full article

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18 pages, 1682 KB

Open AccessSystematic Review

Comparative Effectiveness and Safety of Monotherapy and Defined Combination Regimens for Stenotrophomonas maltophilia. Infections: A Network Meta-Analysis

by Ming-Ying Ai and Wei-Lun Chang

Germs 2026, 16(1), 7; https://doi.org/10.3390/germs16010007 - 2 Mar 2026

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Abstract

Background: Stenotrophomonas maltophilia is a multidrug-resistant pathogen with limited therapeutic options that predominantly affects critically ill and immunocompromised patients. Trimethoprim–sulfamethoxazole (TMP/SMX) remains the conventional first-line therapy; however, emerging resistance and toxicity concerns necessitate alternative regimens. This study represents, to our knowledge, the first [...] Read more.

Background: Stenotrophomonas maltophilia is a multidrug-resistant pathogen with limited therapeutic options that predominantly affects critically ill and immunocompromised patients. Trimethoprim–sulfamethoxazole (TMP/SMX) remains the conventional first-line therapy; however, emerging resistance and toxicity concerns necessitate alternative regimens. This study represents, to our knowledge, the first network meta-analysis (NMA) comparing the efficacy and safety of clearly defined monotherapy and combination antibiotic regimens for S. maltophilia infections. Materials and methods: A systematic search of PubMed, Cochrane Library, Web of Science, and ClinicalTrials.gov (inception to January 2026) identified eligible randomized-controlled studies and retrospective studies. Data were analyzed using a frequentist random-effects NMA with TMP/SMX as the reference. Evaluated regimens included TMP/SMX, fluoroquinolone (FQ), minocycline (MIN), TMP/SMX + FQ, TMP/SMX + MIN, FQ + MIN and FQ + other. Primary and secondary outcomes were all-cause mortality, clinical cure, and adverse effects. Results: Thirteen retrospective studies encompassing 2980 patients were included. Using TMP/SMX as the reference, network meta-analysis demonstrated heterogeneity in all-cause mortality across antimicrobial regimens. FQ and MIN monotherapies were associated with lower odds of mortality (effect sizes: 0.65, 95% CI: 0.49–0.85 and 0.50, 95% CI: 0.28–0.90), whereas combination therapy with TMP/SMX plus FQ was associated with higher mortality (effect size: 2.93, 95% CI: 1.18–7.31). Treatment ranking based on effect sizes suggested more favorable mortality profiles for MIN and FQ regimsens. No significant differences were observed in clinical cure, while FQ was associated with a lower incidence of adverse effects compared with TMP/SMX. Conclusions: This network meta-analysis suggests that FQ and MIN monotherapies may be associated with more favorable survival and tolerability compared with TMP/SMX monotherapy. No clear differences were observed for combination therapy relative to other active monotherapy options. Prospective randomized studies are required to validate these observations and to better inform the management of S. maltophilia infections. Full article

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9 pages, 218 KB

Open AccessArticle

The Use of Unproven Drugs for COVID-19 Treatment in People Living with HIV in Central and Eastern Europe

by Blazej Rozplochowski, Justyna D. Kowalska, Arjan Harxhi, Lukas Fleischhans, Sergii Antoniak, Deniz Gokengin, Anna Vassilenko, Kerstin Aimla, Raimonda Matulionyte, Antonios Papadopoulos, Nino Rukhadze, Botond Lakatos, Dalibor Sedlacek, Gordana Dragovic, Marta Vasylyev, David Jilich, Anatonija Verhaz, Nina Yancheva, Josip Begovac, Agata Skrzat-Klapaczynska and Cristiana Oprea Show full author list Hide full author list

Germs 2026, 16(1), 6; https://doi.org/10.3390/germs16010006 - 19 Feb 2026

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Abstract

Early in 2020, the WHO recommended that existing drugs be evaluated as a repurposed resource to fight the SARS-CoV-2 pandemic. Here, we investigate the trends of using repurposed and off-label drugs among people living with HIV in Central and Eastern Europe (CEE). From [...] Read more.

Early in 2020, the WHO recommended that existing drugs be evaluated as a repurposed resource to fight the SARS-CoV-2 pandemic. Here, we investigate the trends of using repurposed and off-label drugs among people living with HIV in Central and Eastern Europe (CEE). From November 2020 to May 2021, data on the clinical outcomes of HIV-positive patients diagnosed with COVID-19 were collected on eCRFs (SurveyMonkey^® platform, Inc. San Mateo, CA, USA). Factors associated with the off-label drugs available at this time (chloroquine, hydroxychloroquine, favipiravir, oseltamivir, and lopinavir/ritonavir) were identified using logistic regression models. Of the 557 HIV-positive patients assessed with COVID-19 disease, 67 (12.0%) received off-label drugs, as well as 11.6% (16/138) of hospitalized and 12.2% (51/419) of ambulatory patients (p = 0.8564). In the adjusted logistic regression model, higher odds of off-label drug use were found in patients who had their diagnoses confirmed by an RT PCR test (aOR 5.08 [95%CI 1.17–22.0], p = 0.0396), and who came from a non-EU region (aOR 6.79 [95%CI 3.51–13.1], p < 0.0001). The only factor decreasing the odds of off-label drug use was co-infection (aOR 0.31 [95%CI 0.10–0.94], p < 0.0395). In a cohort of HIV patients from the CEE, 12% were prescribed off-label drugs for COVID-19. Symptomatic patients with confirmed SARS-CoV-2 infection or who were from non-EU countries were more likely to receive a repurposed drug. Drug repurposing is an immediate solution to emerging pandemics. All data regarding the safety and effectiveness of such use should be monitored, reported, and publicly available. Access patterns within and outside the EU should be analyzed to prevent potential inequalities in access to care during epidemics in European settings. Full article

9 pages, 606 KB

Open AccessBrief Report

Burkholderia cepacia Complex Comprising Divergent Strains Identified as a Dominant Cause of Pediatric Bloodstream Infections in Myanmar

by Thida San, Meiji Soe Aung, Nan Aye Aye Oo, Linn Linn Htun, Myat Myint Zu Aung, Lynn Waddy and Nobumichi Kobayashi

Germs 2026, 16(1), 5; https://doi.org/10.3390/germs16010005 - 9 Feb 2026

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Abstract

Burkholderia cepacia complex (Bcc) consists of genetically diverse species having highly pathogenic potential to humans, causing nosocomial infections via environmental sources. In Myanmar, Bcc has been known as one of the common pathogens of infectious diseases, with relatively low prevalence. However, recently, an [...] Read more.

Burkholderia cepacia complex (Bcc) consists of genetically diverse species having highly pathogenic potential to humans, causing nosocomial infections via environmental sources. In Myanmar, Bcc has been known as one of the common pathogens of infectious diseases, with relatively low prevalence. However, recently, an increase in isolation from bloodstream infections was noted in a pediatric hospital in Yangon. From December 2023 to June 2025, among the organisms isolated from blood samples (n = 586), Bcc was the most dominant species (n = 178, 30.4%), followed by Klebsiella pneumoniae (16.4%) and Candida spp. (12.7%). Species of Bcc and their genetic types were identified by sequence analysis of partial recA and gyrB genes. Based on the recA sequence, Bcc isolates were identified as B. cepacia (49%), B. cenocepacia (43%), and B. contaminans (7%), having 10, 3, and 2 recA-allelic types, respectively. Similarly, sequences of gyrB revealed the three Bcc species with multiple allelic types. Ceftazidime MIC > 32 mg/L and meropenem MIC > 16 mg/L were found in 38% and 34% of Bcc isolates, respectively. These findings indicated that Bcc, comprising three species with genetically diverse clones, has become the main cause of bloodstream infections in the pediatric hospital in Myanmar. Full article

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13 pages, 257 KB

Open AccessArticle

Factors Associated with Transfer to Intensive Care in Younger Adults Hospitalized with COVID-19

by Philip Tenchev, Emilia Naseva and Nina Yancheva

Germs 2026, 16(1), 4; https://doi.org/10.3390/germs16010004 - 30 Jan 2026

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Abstract

Background/Objectives: While COVID-19 severity is strongly associated with older age, younger adults may also develop complications. This study investigated factors associated with transfer to ICU in hospitalized younger adults during May–December 2021. Materials and methods: Eighty-six consecutive patients aged ≥18 and <50 years [...] Read more.

Background/Objectives: While COVID-19 severity is strongly associated with older age, younger adults may also develop complications. This study investigated factors associated with transfer to ICU in hospitalized younger adults during May–December 2021. Materials and methods: Eighty-six consecutive patients aged ≥18 and <50 years were admitted to the University Multi-profile Hospital for Active Treatment of Infectious and Parasitic Diseases “Prof. Ivan Kirov”, Sofia, Bulgaria between 12 May 2021, and 7 December 2021. Results: Among 86 patients (median age 40 years; 55.8% female), common symptoms included fever (89.5%), cough (91.9%), headache (76.7%), and gastrointestinal symptoms (83.7%). Laboratory abnormalities were frequent: lymphopenia (median 0.94 × 10⁹/L), elevated CRP (28.9 mg/L), LDH (333 U/L), and ferritin (198.5 µg/L). Severe andcritical disease occurred in 17.5% of cases, with 43% requiring oxygen therapy. In descriptive/univariate analyses, ICU transfer was more frequent among patients with hypoxemia (SaO₂ < 90%) and higher CRP, D-dimer, vomiting and ferritin. In a Firth penalized logistic regression model (rare-event setting), endocrine/metabolic comorbidity showed a directionally consistent association with ICU transfer; gastrointestinal comorbidity signals were not interpretable because of extremely small cell counts. Conclusions: Younger adults usually present with mild to moderate COVID-19; however, a substantial minority develop severe illness. Hypoxemia and elevated inflammatory and coagulation markers were consistently associated with worse outcomes. Endocrine/metabolic comorbidity showed the most consistent association with transfer to ICU in this cohort, although all comorbidity estimates should be interpreted cautiously, given the small number of events. Full article

8 pages, 227 KB

Open AccessArticle

Comparative Analysis of Direct Hospital Costs for Community Acquired Viral Gastroenteritis in Children Under 60 Months in Brasov, Romania

by Ioana Arbanaș, Gabriela Coja, Vlad Monescu, Bianca Elena Popovici, Ileana-Raluca Lixandru and Oana Falup-Pecurariu

Germs 2026, 16(1), 3; https://doi.org/10.3390/germs16010003 - 19 Jan 2026

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Abstract

Background/Objectives: Viral gastroenteritis leads to a broad range of hospitalization costs globally in children, depending on the region. To our knowledge, no recent studies have examined the hospitalization cost associated with viral gastroenteritis in Romania. The aim of this study is to determine [...] Read more.

Background/Objectives: Viral gastroenteritis leads to a broad range of hospitalization costs globally in children, depending on the region. To our knowledge, no recent studies have examined the hospitalization cost associated with viral gastroenteritis in Romania. The aim of this study is to determine the direct hospitalization cost of community-acquired viral gastroenteritis (rotavirus, adenovirus and norovirus) in children admitted to Children’s Clinical Hospital of Brașov, Romania, for one year. Methods: All children aged 0–60 months hospitalized for a stool sample positive for rotavirus, adenovirus or norovirus during January 2023 and December 2023 were included in this study. Hospital-acquired gastroenteritis, gastrointestinal coinfections or children with acute coinfection were excluded. The stool specimens were tested using the immunochromatography method. Results: Out of the total of 282 children, 218 children presented rotavirus gastroenteritis, 35 children presented adenovirus gastroenteritis and 29 children presented norovirus gastroenteritis. Regarding patient characteristics, a higher proportion of boys than girls was observed in all three comparison groups, the average age for children with rotavirus was 22.2 months vs. norovirus and adenovirus, and children presented an average age of 16.4 months. Average hospitalization length of stay for rotavirus was 4.64 (±1.95) days, for adenovirus it was 4.54 (±1.52) days and for norovirus it was 4.75 (±1.93) days. Direct hospitalization costs did not differ between rotavirus, adenovirus, and norovirus infections (Kruskal–Wallis H(2) = 0.145, p = 0.930). Conclusions: In this single-center study, rotavirus remained the most frequent cause of viral gastroenteritis requiring hospitalization in young children, followed by adenovirus and norovirus. Although the average length of stay was similar across groups, hospitalization costs varied, with rotavirus-associated cases showing the highest mean expenses and widest cost variability. Full article

9 pages, 375 KB

Open AccessArticle

Variety of Clostridioides difficile Ribotypes in CDI Patients in Las Vegas, NV

by Amber Consul, Mohamad Mubder, Samrawit Misiker, Shadaba Asad, Kimberly D. Leuthner, Chia-Dan Kang, Yassin Shams Eldien Naga, Chad L. Cross and Ernesto Abel-Santos

Germs 2026, 16(1), 2; https://doi.org/10.3390/germs16010002 - 23 Dec 2025

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Abstract

Objective: Although Las Vegas is a major tourist hub, it is not among the counties that are under CDC surveillance for Clostridioides difficile infection (CDI), a major nosocomial infection. To determine the distribution of C. difficile ribotypes in the Las Vegas area, we [...] Read more.

Objective: Although Las Vegas is a major tourist hub, it is not among the counties that are under CDC surveillance for Clostridioides difficile infection (CDI), a major nosocomial infection. To determine the distribution of C. difficile ribotypes in the Las Vegas area, we collected stool samples from CDI-positive patients at the University Medical Center (UMC). Methods: We included adult patients diagnosed with CDI and provided informed consent. C. difficile was isolated from the stool samples and ribotyped. Demographic information was also obtained and analyzed. All information was compared to the surveillance data from the CDC. Results: We identified more frequently in male patients than in the CDC data. Less than half of the patients used antibiotics prior to the infection. We observed several comorbidities in our patient sample pool, with cardiovascular disease and diabetes being the most prevalent comorbidities. Hypervirulent C. difficile strain 027 was the most prevalent ribotype. Except for two samples of ribotype 076, all other samples represented unique singlet ribotypes. Four of these ribotypes (160, 302, 363, and 813) have not been explicitly reported in humans. Conclusions: Due to the unique environment created by the tourism industry in Las Vegas, this population is exposed to national and international visitors. This study shows the pre-COVID landscape of C. difficile ribotypes in Las Vegas and offers valuable insights into the varieties of C. difficile that are currently infecting this community. Full article

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16 pages, 1540 KB

Open AccessArticle

Impact of Manganese Coordination and Cyclodextrin-Assisted Formulation on Thiabendazole Dissolution and Endothelial Cell Migration

by Carmen-Ecaterina Leferman, Lacramioara Ochiuz, Laura Stoica, Liliana Georgeta Foia, Bogdan Minea, Cezar Ilie Foia, Victor Constantinescu, Oana Olariu, Alin Dumitru Ciubotaru and Bogdan Alexandru Stoica

Germs 2026, 16(1), 1; https://doi.org/10.3390/germs16010001 - 22 Dec 2025

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Abstract

Background: Thiabendazole (TBZ), a benzimidazole with established antifungal and anthelmintic properties, has also been reported to exert antiangiogenic effects relevant to tissue remodeling and chronic inflammatory microenvironments. The present study examined how manganese coordination and cyclodextrin modify the dissolution behavior and endothelial activity [...] Read more.

Background: Thiabendazole (TBZ), a benzimidazole with established antifungal and anthelmintic properties, has also been reported to exert antiangiogenic effects relevant to tissue remodeling and chronic inflammatory microenvironments. The present study examined how manganese coordination and cyclodextrin modify the dissolution behavior and endothelial activity of TBZ. Methods: Antiangiogenic potential was assessed through a human umbilical vein endothelial cells (HUVECs) scratch-wound migration assay. Dissolution profiles of TBZ, manganese–thiabendazole (MnTBZ), and MnTBZ/monochlorotriazynil-β-cyclodextrin (MCT-β-CD) formulation were evaluated under biorelevant pH conditions (1.2, 4.5, 6.8, 7.4) using the paddle method. Results: TBZ displayed a more rapid and extensive dissolution at pH 1.2, compared to MnTBZ. Partial dissociation at pH 4.5 modestly improved TBZ availability, while dissolution remained minimal at neutral pH. MCT-β-CD enhanced the solubility of MnTBZ at pH ≥ 6.8. In agreement with these profiles, TBZ exerted the strongest inhibition of endothelial migration, followed by MnTBZ/MCT-β-CD and MnTBZ. Conclusions: Manganese coordination and cyclodextrin formulation modulate both the dissolution behavior and endothelial migration-inhibitory activity of TBZ, suggesting that such formulation approaches may influence the delivery-related and functional properties of benzimidazole derivatives. Full article

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Germs, Volume 16, Issue 1 (March 2026) – 8 articles

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