Germs

17 pages, 965 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

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 [...] 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

17 pages, 665 KB

Open AccessReview

Tubo-Ovarian Abscess, Sepsis and Diffuse Peritonitis in Pelvic Inflammatory Disease—A Diagnostic and Therapeutic Review

by Yavor Kornovski, Stoyan Kostov, Yonka Ivanova, Stanislav Slavchev, Angel Yordanov and Eva Tsoneva

Germs 2025, 15(4), 6; https://doi.org/10.3390/germs15040006 - 18 Dec 2025

Abstract

Background: Pelvic inflammatory disease (PID) is a common and potentially severe infection of the upper genital tract. Complications such as tubo-ovarian abscess (TOA), sepsis, and diffuse peritonitis contribute significantly to reproductive morbidity, particularly when diagnosis or treatment is delayed. Aim: The aim of [...] Read more.

Background: Pelvic inflammatory disease (PID) is a common and potentially severe infection of the upper genital tract. Complications such as tubo-ovarian abscess (TOA), sepsis, and diffuse peritonitis contribute significantly to reproductive morbidity, particularly when diagnosis or treatment is delayed. Aim: The aim of this review is to present an updated, clinically relevant synthesis of the current evidence on the epidemiology, microbiology, diagnostic approach, imaging modalities, and management of PID, with a focus on severe forms including TOA, sepsis, and peritonitis. Content: PID is most frequently initiated by sexually transmitted pathogens—primarily Chlamydia trachomatis and Neisseria gonorrhoeae—which rapidly progresses to a polymicrobial infection involving anaerobic and enteric organisms. Diagnosis is predominantly clinical, supported by nucleic acid amplification tests, inflammatory markers, and imaging. Transvaginal ultrasonography remains the first-line diagnostic approach for suspected TOA, while CT or MRI is reserved for unclear cases or to assess rupture. Mild to moderate disease is managed with broad-spectrum combination antibiotics, whereas severe PID or TOA requires hospitalization, parenteral therapy, and timely source control through image-guided drainage or surgery. Ruptured abscesses and PID-associated sepsis demand urgent surgical intervention and multidisciplinary supportive care. Tailored approaches are necessary in pregnancy, adolescence, and immunosuppressed and postmenopausal patients. Conclusions: Prompt recognition, a low threshold for empiric antimicrobial therapy, the appropriate use of imaging, and decisive escalation to drainage or surgery are essential to limit morbidity and preserve reproductive health. Integrating guideline-based practice with structured clinical pathways may improve outcomes and reduce long-term sequelae of PID. Full article

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15 pages, 564 KB

Open AccessArticle

Early Bacterial Infections After Liver Transplantation: Risk Factors, Microbiological Spectrum, and Outcomes in an Eastern European Cohort

by Iulian Buzincu, Mihaela Blaj, Eliza Isabela Buzincu, Adi-Ionuț Ciumanghel, Irina Gîrleanu, Irina Ciumanghel, Ana-Maria Trofin, Vlad Nuțu, Alexandru Năstase, Ramona Cadar, Vlad Carp, Beatrice Cobzaru, George Mălureanu, Corina Lupașcu Ursulescu and Cristian Dumitru Lupașcu

Germs 2025, 15(4), 5; https://doi.org/10.3390/germs15040005 - 16 Dec 2025

Abstract

Early bacterial infections (EBI) remain a major cause of morbidity and mortality after liver transplantation (LT). This study aimed to characterize their incidence, microbiological spectrum, risk factors, and clinical impact in an Eastern European cohort. We retrospectively analyzed 64 adult LT recipients from [...] Read more.

Early bacterial infections (EBI) remain a major cause of morbidity and mortality after liver transplantation (LT). This study aimed to characterize their incidence, microbiological spectrum, risk factors, and clinical impact in an Eastern European cohort. We retrospectively analyzed 64 adult LT recipients from a tertiary center, focusing on perioperative parameters, infection profiles, and postoperative outcomes. EBI, defined as infections occurring within 30 days after transplantation and diagnosed according to CDC/NHSN criteria, occurred in 48.4% of patients. Gram-negative bacilli predominated (73.7%), mainly Pseudomonas aeruginosa (34.2%) and Klebsiella pneumoniae (15.8%), while Clostridioides difficile (CDI) accounted for 18.4% of confirmed cases diagnosed by stool toxin assay. Infected patients had greater intraoperative blood loss (median 6500 mL vs. 5000 mL, p = 0.036) and required more transfusions. The higher infection rate in our cohort may also be related to longer surgical duration. All deaths within the first postoperative year occurred among infected recipients, yet overall 30-day (7.8%) and 1-year (14.1%) mortality rates remained within the range reported internationally, suggesting that timely diagnosis and adequate management limited the impact of infections on survival. These findings emphasize the importance of infection prevention, optimized transfusion and bleeding control, and tailored antibiotic prophylaxis based on local microbiological patterns after LT. Full article

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16 pages, 1202 KB

Open AccessArticle

Dynamics of Anxiety, Depression, and Sleep Quality Following COVID-19 Hospitalization in Romania

by Mihaela-Camelia Vasile, Catalin Plesea-Condratovici, Mariana Stuparu-Cretu, Anca-Adriana Arbune, Claudiu-Ionut Vasile and Manuela Arbune

Germs 2025, 15(4), 4; https://doi.org/10.3390/germs15040004 - 15 Dec 2025

Abstract

Background: COVID-19 has been associated with neurological and psychiatric manifestations, both at disease onset and during post-infectious sequelae, such as anxiety, depression, and sleep disturbances. Previous pandemics suggest potential for long-term neuropsychiatric consequences. Materials and Methods: We conducted a prospective longitudinal study in [...] Read more.

Background: COVID-19 has been associated with neurological and psychiatric manifestations, both at disease onset and during post-infectious sequelae, such as anxiety, depression, and sleep disturbances. Previous pandemics suggest potential for long-term neuropsychiatric consequences. Materials and Methods: We conducted a prospective longitudinal study in patients hospitalized with non-critical COVID-19, evaluating symptoms using validated psychometric instruments at discharge and after 3–6 and 12 months post-infection. Additionally, a four-year follow-up was performed through telephone interviews to document newly diagnosed psychiatric disorders and mortality. Results: At baseline, 22% of patients reported anxiety, 8% depression, and 16% poor sleep. Most symptoms improved within the first year, particularly during the first 3–6 months. At four-year follow-up, mortality reached 5%, while clinician-diagnosed psychiatric disorders increased to 6% for anxiety, 11% for depression, and 3% for mixed disorders. Anxiety and poor sleep—but not depression—were associated with the severity of the acute episode. Conclusions: Overall, post-COVID-19 anxiety, depression, and sleep disturbances were more prevalent than in the general population, though the rates were lower than those reported in other studies. Most symptoms resolved within the first year. However, new-onset cases of depression and other psychiatric disorders emerged during long-term follow-up, suggesting distinct trajectories of post-COVID-19 psychiatric morbidity. Full article

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8 pages, 209 KB

Open AccessCase Report

Typhoid Fever in a Non-Endemic Country: Diagnostic and Therapeutic Challenges in a Returning Traveler

by Ekaterina Lyutsova, Teodora Stoyanova, Andi Isidro, Iliyan Todorov and Diana Radkova

Germs 2025, 15(4), 3; https://doi.org/10.3390/germs15040003 - 10 Nov 2025

Abstract

Background: Typhoid fever (TF) is a systemic infection caused by Salmonella enterica serovar Typhi, typically associated with regions where sanitation and access to clean water are inadequate. Although rare in non-endemic countries, TF remains a diagnostic consideration in travelers returning from endemic areas [...] Read more.

Background: Typhoid fever (TF) is a systemic infection caused by Salmonella enterica serovar Typhi, typically associated with regions where sanitation and access to clean water are inadequate. Although rare in non-endemic countries, TF remains a diagnostic consideration in travelers returning from endemic areas with febrile illness. Case report: We present the case of an 18-year-old female who developed TF following recent travel to Nigeria. The initial clinical presentation, including fever, dysuria, and abdominal pain, led to a misdiagnosis of acute pyelonephritis. Malaria, arboviral infections, acute viral hepatitis, and parasitic diseases were systematically ruled out through clinical evaluation, serological testing, and parasitological analysis. The clinical course was marked by fever, abdominal pain, somnolence, and hematological and hepatic abnormalities. Blood cultures confirmed the diagnosis, with the isolate verified and serotyped by the National Center of Infectious and Parasitic Diseases. Targeted antimicrobial treatment with ceftriaxone and levofloxacin resulted in full recovery, with no evidence of relapse or chronic carriage over a three-month follow-up period. Conclusions: This case highlights the critical importance of a structured differential diagnostic approach and microbiological confirmation in febrile patients with relevant travel history. In non-endemic settings, where TF may be underrecognized, early recognition, pathogen identification, and appropriate antimicrobial therapy remain essential to favorable outcomes and public health safety. Full article

2 pages, 172 KB

Open AccessEditorial

Building on Strong Foundations: A Message from the Editor-in-Chief of Germs

by Oana Săndulescu

Germs 2025, 15(4), 2; https://doi.org/10.3390/germs15040002 - 15 Oct 2025

Abstract

It is with both gratitude and anticipation that I write these words, looking back on almost 15 years of continued publication and marking the transition of Germs into a new chapter through our collaboration with MDPI [...] Full article

1 pages, 162 KB

Open AccessEditorial

Publisher’s Note: A New Chapter for Germs—Continued Publication by MDPI

by Clàudia Aunós

Germs 2025, 15(4), 1; https://doi.org/10.3390/germs15040001 - 1 Oct 2025

Abstract

We are pleased to announce that, beginning with Volume 15, Issue 4 (2025), Germs (ISSN: 2248-2997) will now be published by MDPI [...] Full article

4 pages, 187 KB

Open AccessCommunication

Innovative Approaches in RSV Prevention: The Expanding Role of Monoclonal Antibodies in Protection for All Infants

by Florin-Dumitru Mihălţan, Ruxandra Ulmeanu, Roxana-Maria Nemeş, Sorin Petrea, Anca Streinu-Cercel and Oana Săndulescu

Germs 2025, 15(3), 279-282; https://doi.org/10.18683/germs.2025.1475 - 30 Sep 2025

Cited by 1

Abstract

Respiratory syncytial virus (RSV) continues to be a predominant cause of lower respiratory tract infections among infants and toddlers, posing a substantial burden on pediatric health and healthcare systems worldwide. Full article

5 pages, 396 KB

Open AccessCase Report

Multidrug-Resistant Acinetobacter baumannii Meningitis and Cerebellar Abscess: Case Report and Therapeutic Considerations

by Maria-Elena Vodarici, Nicola-Maria Militaru, Lucia Zekra, Nicoleta Chipăilă, Oana-Elena Ioniţă, Andra-Elena Petcu, Roxana-Carmen Cernat, Bogdan Florentin Niţu, Simona Claudia Cambrea and Irina-Magdalena Dumitru

Germs 2025, 15(3), 274-278; https://doi.org/10.18683/germs.2025.1474 - 30 Sep 2025

Abstract

Introduction: Brain abscess is defined as a suppurative collection resulting from hematogenous dissemination as an extension from otorhinolaryngologic infectious foci, or secondary to cranial trauma and neurosurgical procedures. Its evolution follows four histopathological stages, the most severe complication being intraventricular rupture, which is [...] Read more.

Introduction: Brain abscess is defined as a suppurative collection resulting from hematogenous dissemination as an extension from otorhinolaryngologic infectious foci, or secondary to cranial trauma and neurosurgical procedures. Its evolution follows four histopathological stages, the most severe complication being intraventricular rupture, which is associated with extremely high mortality. Central nervous system infections caused by multidrug-resistant (MDR/XDR) Acinetobacter baumannii are rare but severe, significantly limiting therapeutic options due to the reduced penetration of the blood-brain barrier by active antimicrobial agents. Case report: We report the case of a 48-year-old patient with a history of hemorrhagic stroke treated surgically, who was admitted for fever, severe headache, and vomiting. On admission, lumbar puncture confirmed bacterial meningitis, with isolation of A. baumannii susceptible only to colistin. Brain magnetic resonance imaging revealed a postoperative cerebellar abscess. Initial empirical therapy consisted of meropenem and vancomycin, subsequently adjusted according to the susceptibility profile to cefiderocol, intravenous and intrathecal colistin, combined with ampicillin/sulbactam and minocycline. The clinical course was favorable with regard to meningitis, with partial regression of the cerebellar abscess. Follow-up lumbar punctures were sterile, and the patient’s neurological condition stabilized, allowing avoidance of neurosurgical drainage. Conclusions: Meningitis and brain abscess caused by MDRA. baumannii represent rare clinical entities with potentially severe outcomes. Intrathecal administration of colistin, in combination with systemic multidrug therapy, proved decisive in controlling the infection. An interdisciplinary approach and individualized antimicrobial regimens are essential to achieving a favorable prognosis in such complex cases. Full article

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11 pages, 323 KB

Open AccessReview

Evolving Insights into Viral Hepatitis: Advances, Evidence, and Expert Perspectives from the ESCMID Study Group for Viral Hepatitis (ESGVH)—Part 2: Hepatitis B, C, and Delta

by Oana Săndulescu, Mojca Matičič, Federico Garcia, Marianne Alanko Blomé, Mario U Mondelli, William Irving, Snjezana Zidovec-Lepej, Anders Widell and Gülşen Özkaya Şahin

Germs 2025, 15(3), 263-273; https://doi.org/10.18683/germs.2025.1473 - 30 Sep 2025

Abstract

Hepatitis B virus (HBV), hepatitis delta virus (HDV), and hepatitis C virus (HCV) remain leading drivers of chronic viral hepatitis, cirrhosis, hepatocellular carcinoma, and liver-related mortality. This ESCMID Study Group for Viral Hepatitis (ESGVH) narrative review summarizes recent advances and expert perspectives in [...] Read more.

Hepatitis B virus (HBV), hepatitis delta virus (HDV), and hepatitis C virus (HCV) remain leading drivers of chronic viral hepatitis, cirrhosis, hepatocellular carcinoma, and liver-related mortality. This ESCMID Study Group for Viral Hepatitis (ESGVH) narrative review summarizes recent advances and expert perspectives in the field. For HBV, emerging biomarkers such as quantitative HBs antigen, HBV RNA, and hepatitis B core-related antigen offer opportunities to refine monitoring and to individualize treatment. HDV epidemiology is evolving, and is being increasingly studied; in parallel, the approval of bulevirtide represents a major breakthrough in therapy, with further agents in the HDV pipeline. For HCV, direct-acting antivirals provide curative therapy and have made elimination a realistic goal, while identifying remaining gaps in diagnosis, linkage-to-care, and equitable access offers clear opportunities to accelerate progress. Together, these advances bring the goal of a hepatitis-free future closer than ever. Full article

9 pages, 284 KB

Open AccessReview

Evolving Insights into Viral Hepatitis: Advances, Evidence, and Expert Perspectives from the ESCMID Study Group for Viral Hepatitis (ESGVH)—Part 1: Hepatitis A, E, and Herpesvirus-Associated Liver Disease

by Oana Săndulescu, Mojca Matičič, Federico Garcia, Marianne Alanko Blomé, Mario U Mondelli, William Irving, Snjezana Zidovec-Lepej, Anders Widell and Gülşen Özkaya Şahin

Germs 2025, 15(3), 254-262; https://doi.org/10.18683/germs.2025.1472 - 30 Sep 2025

Abstract

Viral hepatitis remains a global health concern, with growing recognition of the impact of hepatitis A virus (HAV), hepatitis E virus (HEV), and herpesvirus-associated hepatitis, particularly in vulnerable groups. This narrative review from the ESCMID Study Group for Viral Hepatitis (ESGVH) summarizes recent [...] Read more.

Viral hepatitis remains a global health concern, with growing recognition of the impact of hepatitis A virus (HAV), hepatitis E virus (HEV), and herpesvirus-associated hepatitis, particularly in vulnerable groups. This narrative review from the ESCMID Study Group for Viral Hepatitis (ESGVH) summarizes recent advances and expert perspectives. For HAV, insights into viral evolution, epidemiology, and risk groups underline the preventable nature of severe disease. HEV is increasingly recognized as both a hepatotropic and a systemic pathogen, with expanding knowledge on natural and vaccine-induced immunity. Herpesvirus-associated hepatitis, while rare, poses significant challenges, especially in patients with immunosuppression or during pregnancy, where early suspicion and empirical antiviral therapy can be lifesaving. Collectively, these evolving insights highlight the importance of strengthened diagnostics, targeted prevention, and tailored management strategies to mitigate the burden of these underappreciated but clinically significant causes of viral hepatitis. Full article

12 pages, 312 KB

Open AccessArticle

A Literature Review of Influenza Chemoprophylaxis and Treatment in Children

by Ioana Luca, Elena Diana Andone, Ioana Arbanas, Laura Bleotu and Oana Falup Pecurariu

Germs 2025, 15(3), 242-253; https://doi.org/10.18683/germs.2025.1471 - 30 Sep 2025

Abstract

Influenza remains a common cause of hospitalization among children, bringing substantial morbidity and mortality rates. Despite its soaring prevalence, a significant gap in therapeutic interventions persists, especially for the pediatric population. We present a literature review detailing clinical trials or case reports published [...] Read more.

Influenza remains a common cause of hospitalization among children, bringing substantial morbidity and mortality rates. Despite its soaring prevalence, a significant gap in therapeutic interventions persists, especially for the pediatric population. We present a literature review detailing clinical trials or case reports published in the last six years (since 2019) that discuss the prevention or treatment of influenza in children. We used search engines such as PubMed or Cochrane Library. All studies/case reports are written in English, and all the clinical trials are finished. In Europe, oseltamivir, zanamivir, and baloxavir marboxil are recommended for the treatment or prophylaxis of influenza in adults and children, while the Food and Drug Administration added intravenous peramivir to the list of anti-influenza drugs. Oseltamivir remains the first line of treatment and chemoprophylaxis. However, there are still discussions related to the duration of prophylaxis, with shorter periods of administration being explored, or the most efficient treatment dosage program (whether it is the conventional dosage of 3 mg/kg/dose for children <40 kg or 75 mg for adults, twice daily, compared to a double dosage administration program). When faced with an old disease, it is essential to constantly assess the efficacy of conventional molecules and dosages, along with new antivirals or complementary medication. Full article

21 pages, 1326 KB

Open AccessArticle

Consensus Statement: Updated Recommendations for the Interdisciplinary Management of People Living with HIV in Romania

by Oana Săndulescu, Anca Streinu-Cercel, Mariana Mărdărescu, Cristiana Oprea, Maria Dorobanţu, Gener Ismail, Aura Diana Reghina, Odette Chirilă, Extended Consensus Group and Adrian Streinu-Cercel

Germs 2025, 15(3), 221-241; https://doi.org/10.18683/germs.2025.1470 - 30 Sep 2025

Abstract

Owing to significant advances in HIV treatment and the resultant increase in life expectancy, the number of aging individuals living with HIV and associated comorbidities continues to rise. Consequently, the management of people living with HIV is no longer solely the responsibility of [...] Read more.

Owing to significant advances in HIV treatment and the resultant increase in life expectancy, the number of aging individuals living with HIV and associated comorbidities continues to rise. Consequently, the management of people living with HIV is no longer solely the responsibility of infectious disease or HIV specialists, but requires an integrated and multidisciplinary approach that addresses the prevention, as well as the monitoring and treatment needs of associated conditions. The care of people living with HIV in Romania is largely aligned with international guidelines, particularly those of the European AIDS Clinical Society (EACS). However, guideline implementation requires adaptation to local clinical realities and collaboration across medical specialties. In response to this need, a team of experts in infectious diseases, cardiology, nephrology, diabetes, metabolic disorders, and clinical psychology, convened to develop a national consensus for the interdisciplinary management of people living with HIV. The consensus provides clear and practical recommendations addressed to both infectious disease specialists and healthcare providers from other specialties involved in the care of people living with HIV. Its goal is to offer a unified, up-to-date, and applicable framework to support patient-centered care, facilitate interdisciplinary collaboration, and contribute to improving the quality of life of people living with HIV in Romania. Full article

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5 pages, 212 KB

Open AccessArticle

Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Treatment in People Living with HIV: A Single-Center Real-World Experience from Belgrade, Serbia

by Marko Markovic, Jovan Ranin, Aleksa Despotovic, Ivan Rajkovic, Jovana Ranin, Milan Tanasijevic, Nikola Mitrovic, Natasa Nikolic, Ivana Milosevic and Ivana Gmizic

Germs 2025, 15(3), 216-220; https://doi.org/10.18683/germs.2025.1469 - 30 Sep 2025

Abstract

Introduction: Doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) is recommended for both ART initiation and switch in virologically suppressed patients. We report early real-world outcomes after DOR/3TC/TDF introduction in Belgrade, Serbia. Methods: We conducted a single-center retrospective study at the Clinic for Infectious and Tropical Diseases, [...] Read more.

Introduction: Doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) is recommended for both ART initiation and switch in virologically suppressed patients. We report early real-world outcomes after DOR/3TC/TDF introduction in Belgrade, Serbia. Methods: We conducted a single-center retrospective study at the Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, including all adults who initiated or switched to DOR/3TC/TDF between May 2024 and April 2025. Demographics, comorbidities, prior ART, adverse events, and laboratory data (CD4, HIV-1 RNA, triglycerides, total and LDL cholesterol) were abstracted from electronic records. Results: Of 260 participants, 75 were treatment-naïve and 185 switched regimens; median follow-up was 7 months (IQR: 1-11 months). In naïve patients, CD4 counts increased (458.2±312.0 to 580.7±262.8 cells/µL; p=0.007) and viral load fell to undetectable in 82.8% (24/29; p=0.002). In switch patients, CD4 counts remained stable (665.0±317.5 to 660.5±268.0; p=0.891) and suppression was maintained, with rates of undetectable viral load rising from 83.2% to 93.1% (p=0.013). No significant short-term changes were observed in triglycerides, total cholesterol, or LDL. No virological failures occurred; one discontinuation due to rash was recorded. Conclusions: In routine care in Belgrade, once-daily DOR/3TC/TDF was well tolerated and effective: naïve patients achieved rapid suppression with CD4 gains, and switch patients maintained high rates of undetectable viral load without adverse lipid shifts. These findings support DOR/3TC/TDF as a practical option in the Serbian setting. Full article

7 pages, 313 KB

Open AccessArticle

One-Year Surveillance of Last-Resort Antimicrobial Resistance Patterns in Carbapenemase-Producing Klebsiella pneumoniae Strains Isolated in a Romanian Tertiary Care Hospital: A Prospective Study

by Mihai Octavian Dan, Dragoş Florea, Alexandru Rafila, Mihai Turcitu, Dan Florin Turcitu and Daniela Tălăpan

Germs 2025, 15(3), 209-215; https://doi.org/10.18683/germs.2025.1468 - 30 Sep 2025

Abstract

Introduction: Antimicrobial resistance is a significant public health issue worldwide, associated with limited treatment options and with major consequences for healthcare systems. Our study aims to assess rates and patterns of resistance to five last-resort antimicrobials in a cohort of carbapenemase-producing Klebsiella pneumoniae [...] Read more.

Introduction: Antimicrobial resistance is a significant public health issue worldwide, associated with limited treatment options and with major consequences for healthcare systems. Our study aims to assess rates and patterns of resistance to five last-resort antimicrobials in a cohort of carbapenemase-producing Klebsiella pneumoniae strains, isolated over a one-year interval. Additionally, we have tested two potentially synergistic combinations for in vitro efficacy. Methods: This prospective observational study evaluated Klebsiella pneumoniae strains with diminished carbapenem susceptibility from patients admitted to the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” in Bucharest between August 2023 and July 2024. Strains presenting a minimum inhibitory concentration to meropenem of >0.125 μg/mL underwent phenotypic enzyme production testing, followed by synergistic testing to identify antimicrobial salvage therapy options. A subset of these strains was analysed for the detection of plasmid-mediated resistance genes, using a custom workflow for DNA extraction and amplification/detection. Results: A total of 139 non-duplicate strains were isolated, with 129 (92.8%) being carbapenemase producers. These 129 strains were phenotypically diverse: 29 (22.5%) were NDM, 12 (9.3%) OXA-48 type, 8 (6.2%) KPC, while most of them (62.0%) were double carbapenemase producers: 79 (61.2%) NDM and OXA-48-type, and one strain was NDM and KPC. Forty-six strains were resistant to cefiderocol (35.7%), 108 (83.7%) to ceftazidime/avibactam, 127 (98.4%) to ceftolozane/tazobactam, 116 (90.0%) to imipenem/relebactam and 127 (98.4%) to aztreonam. The association of aztreonam with ceftazidime/avibactam demonstrated a synergistic effect in 127 (98.5%) strains, while aztreonam with imipenem/relebactam was efficient in vitro against 103 (79.8%) strains. Conclusions: Antimicrobial resistance remains a concerning phenomenon among Enterobacterales, especially when considering the increasing resistance rates even against salvage therapy antimicrobials. Full article

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Open AccessCase Report

Pulmonary Co-Infection with Pneumocystis jirovecii and Histoplasma capsulatum. Hickam’s Dictum or Occam’s Razor

by Diego Fernando Severiche-Bueno, Silvia J Galvis-Blanco and Jacqueline Mugnier

Germs 2025, 15(2), 189-194; https://doi.org/10.18683/germs.2025.1467 - 30 Jun 2025

Abstract

Introduction: Co-infection with Histoplasma capsulatum and Pneumocystis jirovecii is rarely documented in HIV-negative immunocompromised patients and poses significant diagnostic challenges due to overlapping radiological patterns and limited access to advanced mycological testing. Case report: A 58-year-old woman with systemic lupus erythematosus and lupus [...] Read more.

Introduction: Co-infection with Histoplasma capsulatum and Pneumocystis jirovecii is rarely documented in HIV-negative immunocompromised patients and poses significant diagnostic challenges due to overlapping radiological patterns and limited access to advanced mycological testing. Case report: A 58-year-old woman with systemic lupus erythematosus and lupus nephritis, under treatment with corticosteroids and cyclophosphamide, presented with fever and hypoxemia. Chest computed tomography demonstrated bilateral micronodules, ground-glass opacities, and mediastinal lymphadenopathy. HIV testing and initial cultures were negative. Bronchoalveolar lavage revealed P. jirovecii, prompting the initiation of trimethoprim-sulfamethoxazole. Despite targeted therapy, the patient developed progressive respiratory failure, requiring intensive care. Transbronchial biopsy later confirmed coinfection with H. capsulatum. Antifungal therapy with liposomal amphotericin B and itraconazole was initiated; however, the clinical course was marked by progressive deterioration, culminating in death. Conclusions: This case highlights the need for high clinical suspicion of dual opportunistic infections in non-HIV immunocompromised patients. Diagnostic delays, particularly in resource-limited settings without fungal PCR, may adversely affect outcomes. In such complex hosts, early invasive diagnostics and broader access to rapid molecular testing are critical to improving prognosis in this vulnerable population. Full article

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Open AccessReview

Colistin Heteroresistance, Mechanisms, Diagnostic Methods, and Therapeutic Options: A Review

by Razieh Dehbanipour, Vala Taghi Zadeh Maleki and Zohreh Ghalavand

Germs 2025, 15(2), 166-188; https://doi.org/10.18683/germs.2025.1466 - 30 Jun 2025

Cited by 1

Abstract

The heteroresistance phenotype refers to the presence of bacterial subpopulations with reduced antibiotic susceptibility compared with the main population. Mathematical modelling and computer simulations suggest that heteroresistance can lead to negative treatment outcomes and finally, treatment failure. Due to the low frequency and [...] Read more.

The heteroresistance phenotype refers to the presence of bacterial subpopulations with reduced antibiotic susceptibility compared with the main population. Mathematical modelling and computer simulations suggest that heteroresistance can lead to negative treatment outcomes and finally, treatment failure. Due to the low frequency and resistance level of resistant subpopulations, detection of heteroresistance phenotype in the diagnostic laboratory is problematic. Routine laboratory tests do not have the ability to accurately detect heteroresistance, but on the other hand, specific methods are time consuming and expensive. The emergence of colistin heteroresistance is a public health concern that threatens human health. Colistin heteroresistance to date has been reported in eight pathogens including Acinetobacter spp., Klebsiella spp., Enterobacter spp., Pseudomonas spp., Escherichia coli, Salmonella enterica serovar Typhimurium (referred to as Salmonella Typhimurium), Neisseria meningitidis and Stenotrophomonas maltophilia. The growing emergence of colistin heteroresistance worldwide underscores the crucial need for coordinated global action to combat it. Understanding the mechanisms of colistin heteroresistance can help to provide better guidelines for reducing antibiotic resistance and to achieve new therapeutic approaches. Our review showed that the prevalence of colistin heteroresistance strains varies in different countries. It seems that the use of different treatment strategies, especially combination therapy, can be effective in reducing the incidence of resistant subpopulations. Also, the use of new generation diagnostic methods can have a significant impact on treatment. Our findings in this review are needed to raise the awareness of microbiologists and specialists to the colistin heteroresistance mechanisms and to achieve effective treatment. Full article

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Open AccessArticle

Illicit Drugs—Infections and Neonatal Anthropometric Characteristics

by Leonard Năstase, Silvia-Maria Stoicescu, Nicolae Suciu, Laurenţiu Camil Bohîlţea, Eugenia Panaitescu and Adina-Brânduşa Baciu

Germs 2025, 15(2), 157-165; https://doi.org/10.18683/germs.2025.1465 - 30 Jun 2025

Abstract

Introduction: The effects of drug addiction in pregnancy are associated with multiple maternal, fetal and neonatal risks in the short and long term. Methods: This was a retrospective descriptive study conducted in the National Institute for Maternal and Child Health "Alessandrescu-Rusescu" Bucharest, Romania [...] Read more.

Introduction: The effects of drug addiction in pregnancy are associated with multiple maternal, fetal and neonatal risks in the short and long term. Methods: This was a retrospective descriptive study conducted in the National Institute for Maternal and Child Health "Alessandrescu-Rusescu" Bucharest, Romania - "Polizu" Hospital of Obstetrics and Gynecology (higher level maternity hospital), includes newborns from the last 22 years (2002–2024) from mothers who used illicit drugs before and during pregnancy. Results: The incidence of newborns born to mothers with drug addiction has steadily increased over the period studied, especially in the last 12 years. Neonatal morbidity was marked by: withdrawal syndrome (61.2% of cases), risk of congenital/perinatal infections through maternal infections (58.16%), prematurity (43.87%), birth weight ≤2500 g (55.10%), intrauterine growth restriction. Conclusions: Illicit drug use in pregnancy, associated with prematurity, intrauterine growth restriction, neonatal withdrawal syndrome, risk of congenital/perinatal infections through maternal infections, is an important risk factor for neonatal morbidity and mortality. Full article

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Open AccessArticle

The Status of Hepatitis C Microelimination Among People Living with HIV in Central and Eastern Europe in 2022—Data from Euroguidelines in Central and Eastern Europe Network Group

by Agata Skrzat-Klapaczyńska, Sergii Antoniak, Svitlana Antonyak, Konstantinos Protopapas, Antonios Papadopoulos, Daniela Maric, Botond Lakatos, Antonija Verhaz, Milan Zlamal, Zofia Bartovska, Milena Stefanovikj, Gordana Dragovic, Arjan Harxhi, David Jilich, Kerstin Aimla, Lilia Cojuhari, Justyna Kowalska and Josip Begovac

Germs 2025, 15(2), 144-156; https://doi.org/10.18683/germs.2025.1464 - 30 Jun 2025

Abstract

Introduction: The implementation of nationwide viral hepatitis C elimination programs is challenging in Central and Eastern European countries (CEEC). It is reasonable to start by targeting specific populations, such as people living with HIV (PLWH), who are at higher risk of acquiring HCV [...] Read more.

Introduction: The implementation of nationwide viral hepatitis C elimination programs is challenging in Central and Eastern European countries (CEEC). It is reasonable to start by targeting specific populations, such as people living with HIV (PLWH), who are at higher risk of acquiring HCV or developing HCV-related complications. Methods: Euroguidelines in Central and Eastern Europe Network Group consists of experts in the field of infectious diseases from 26 countries in the region. Between April 26th and June 23rd 2023, the group performed an on-line survey consisting of 32 questions. The questionnaire assessed the status of HCV micro-elimination in 2022. Results: Twelve HIV centers from 11 countries responded: Albania, Bosnia and Herzegovina, Croatia, Czech Republic, Estonia, Greece, Hungary, Macedonia, Moldova, Serbia and Ukraine. All centers screen for HCV antibody all PLWH at entry into care. The seroprevalence of anti-HCV was <5% in 5 centers (Albania, Croatia, Serbia, North Macedonia and Hungary), 30.2% in Estonia and 29% in Ukraine, Greece and Moldova had high seroprevalence as well, 15.3% and 15.6% respectively. The prevalence of HCV viremia in antibody-positive PLWH was very high in Greece (85%), while in most other treatment centers it ranged from 4.2% to 38.2%. There is also a screening policy of annual HCV-testing of HCV-antibody negative persons in all centers by either testing all PLWH or those considered at risk. Direct-acting antiviral agents (DAA) were not available in one country (Albania). Among PLWH who entered care in 2022, nine out of 12 ECEE centers reported cases of HCV/HIV coinfection, with five centers indicating that at least 50% of these individuals were HCV-viremic. Conclusions: HCV screening in PLWH followed by access to DAA treatments were available in all but one center. Microelimination of HCV in PLWH in the majority of surveyed HIV treatment centers in CEEC has not been achieved and efforts to reach this goal need to be strengthened. Full article

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