Volume 33, Issue 1, 2025
Editorial
Ongoing hMPV outbreaks in China and other Asian countries
Sah Ranjit,
Srivastava Shriyansh,
Kumar Sachin,
Rao G. S. N. Koteswara,
Mehta Rachana ,
Mohanty Aroop,
Sah Sanjit,
Mehta Vini,
Feehan Jack,
Apostolopoulos Vasso,
Rodriguez-Morales Alfonso J.
Not available
Review
New antibiotics targeting Gram-negative bacilli
Al-Tawfiq Jaffar A.,
Sah Ranjit,
Mehta Rachana ,
Apostolopoulos Vasso,
Temsah Mohamad-Hani,
Eljaaly Khalid
Antimicrobial resistance (AMR) is an emerging global threat. It increases mortality and morbidity rates and places a heavy burden on healthcare systems. Healthcare professionals can address the increasing issue of AMR by advocating responsible antibiotic use and supporting the development of new medications. Despite the economic, logistic, and scientific challenges, it is reassuring that new agents continue to be developed. This review addresses new antibiotics in the pipeline. A review of the literature was conducted including Medline, and Clinicaltrials.org, for approved and in pipeline antibiotics in phase 3 or new drug applications (NDA). We found several new antibiotics and reviewed their current development status, mode of action, spectra of activity, and indications for which they have been approved. The included studies from phase 3 clinical trials were mainly utilized for the treatment of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and pneumonia acquired in healthcare settings. The availability of these agents is limited for high-priority organisms. The identified antibiotics were primarily based on previously known molecules or pre-existing antimicrobial agents.There is a limited number of antibiotics against high priority organisms. New antimicrobial agents targeting the top-priority organisms identified by the World Health Organization are urgently needed. However, some antibiotics target ESBL-producing Enterobacterales, carbapenem-resistant Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa.
Maternal and foetal outcomes in women with gestational Dengue: A systematic review
Vélez Jaramillo Yanet,
Reveiz Montes Marco Antonio,
Galván-Barrios Johana Patricia,
Picón-Jaimes Yelson Alejandro
Introduction: Dengue is a mosquito-borne viral disease. It has been associated with high maternal and foetal morbidity and mortality. Therefore, this study aimed to describe the outcomes of Dengue infection in pregnant women in terms of maternal bleeding, miscarriage, preterm delivery, severe Dengue, Dengue shock and maternal mortality, as well as foetal outcomes in terms of foetal distress, low birth weight and neonatal mortality.
Methods: This systematic review followed PRISMA guidelines and was PROSPERO-registered (CRD42024578212). It examined publications from 2019-2024 across major databases, including Medline, Scopus, Web of Science, Scielo, and CENTRAL. The selection process utilised Rayyan
AIR for duplicate removal, followed by a two-reviewer screening system. The two reviewers initially filtered the papers by title and, then, by abstract; finally, they read the full text and chose the articles to synthesise. The same two reviewers performed data extraction independently using
a Microsoft ExcelR matrix. For the risk of bias assessment and Quality evaluation, the ROBINS-E tool and the STROBE guidelines were employed.
Results: Maternal Dengue was associated with an increased risk of preterm delivery and complications such as obstetric bleeding, especially postpartum haemorrhage, which was a complication that reached proportions of up to 25% in some studies. Severe Dengue and Dengue shock were also complications present in these women; thrombocytopenia was the most common sign, and complications such as pre-eclampsia and multi-organ dysfunction appeared, leading to fatal outcomes such as maternal and foetal mortality.
Conclusions: Dengue infection during gestation carries significant maternal health risks, including complications such as bleeding, miscarriage and preterm delivery. In addition, it is associated with foetal distress and low birth weight, as well as increased foetal and neonatal mortality, highlighting the need for vigilance and appropriate medical care.
Updates on HIV Pre-exposure Prophylaxis in Latin America: Available Drugs and Implementation Status
Gonzales-Gavancho Christian,
Araoz-Salinas Julieta M.,
Ramon Tapia Ruth,
Quispe-Vicuña Carlos,
Reategui-Garcia Martin E.,
Rios-Garcia Wagner,
Baltodano-Calle Maria Jose,
Belanovic-Ramirez Ivana,
Ortiz-Pardo Allison N.,
Ortiz-Saavedra Brando,
Campos Victor Y. M.,
Alave Jorge,
Gonzales-Zamora Jose A.
Latin America has reported a 9% increase in new HIV infections from 2010 to 2023. Pre-exposure prophylaxis (PrEP) is a crucial biomedical intervention for preventing HIV transmission. Currently, several antiretroviral drugs, in various forms of administration, have demonstrated high efficacy and effectiveness to protect against HIV. Among the oral drugs, we have emtricitabine/tenofovir and emtricitabine/tenofovir alafenamide, while alternative options include the dapivirine vaginal ring, injectable drugs such as Cabotegravir, and the most recently studied Lenacapavir. Despite their high efficacy and effectiveness, implementing PrEP in Latin America has been challenging throughout the region. Although some countries such as Brazil, Mexico, and Colombia have shown progress in increasing the number of users, there is a significant gap between these countries and others where PrEP access remains limited or non-existent. Barriers such as lack of awareness, inadequate funding, political instability, and outdated policies contribute to disparities in access, leaving many populations at high risk of HIV infection without this preventative measure. Innovative strategies need to be implemented to address and monitor policies that ensure access for all at-risk populations.
Dengue in patients with kidney transplant: a systematic review
Salazar-Urbano Andres Felipe,
Sussmann-Peña Otto Alberto,
Guezguan-Perez Jonathan Alexander,
Ortiz-Parra Angie Alejandra,
Cruz-Muñoz Jesika Lorena,
Mosquera-Niño Karol Daniela,
Reyes-Hernández Luis Gabriel,
Rodriguez-Morales Alfonso J.
Introduction: The incidence of dengue and its complications increases globally, mainly in areas where it is endemic; however, little literature evaluates outcomes in kidney transplant recipients (KTR). The present analysis aimed to determine the incidence, signs and symptoms, and allograft dysfunction in dengue-infected KTR.
Methods: Systematic review of the literature following PRISMA 2020 indications with studies included until November 24, 2023.
Results: Of 309 articles found, seven full-text studies were identified for analysis. 4337 KTRs with 214 dengue cases were evaluated. The incidence of dengue was 4.93%, varying between geographic regions. The average age was 41.50 years, and 61.21% were men. A mortality of 7.01% was reported. The symptoms were fever 83.18%, arthralgia 19.46%, myalgia 43.24% and headache 34.18%. The proportions of febrile dengue, with warning signs and severe dengue, were 63.55%, 23.83% and 11.68%, respectively. Transplant dysfunction and loss occurred in 63.08% and 4.67%, respectively.
Conclusions: Although the global distribution of dengue in KTR is unknown, there is a variable incidence between geographical areas and study times in which the KTR are evaluated. There is a high incidence of febrile symptomatology and transplant dysfunction consistent with global cohorts for non-KTR and KTR patients, respectively. Dysfunction is a prevalent event in KTRs with dengue infection, so correct screening should be done for donors and transplant candidates.
Real-world experience with therapies for SARS-CoV-2: Lessons from the Italian COVID-19 studies
Velati Daniela,
Puoti Massimo
The therapeutic armamentarium that has been made available from the beginning of the emergency phase of the COVID-19 pandemic to date is briefly reviewed, and an overview of the real-world clinical evidence published by the Italian medical and scientific community during the last three years is presented herein. Prior to the introduction of a vaccine for SARS-CoV-2, several treatment options were implemented from the onset given the evidence that a “cytokine storm” was present during infection with SARS-CoV-2. However, with the exception of tocilizumab, baricitinib and perhaps anakinra, most studies with anti-cytokine biological agents in patients with severe COVID-19 did not show any significant clinical improvement or decrease in mortality at day 28. The same is true of several repurposed drugs including ivermectin, lactoferrin, interferon ß-1a, lopinavir/ritonavir alone or combined with hydroxychloroquine, and darunavir/cobicistat, which did not show any benefits in clinical status or mortality. Treatment with neutralizing monoclonal antibodies (mAbs) for COVID-19 is changing continually with the evolution of new viral variants. In Italy, current indications for treatment of COVID-19 outpatients underline that the use of specific mAbs may vary over time depending on the prevalent SARSCoV-2 variant and the sensitivity to the different mAbs available. Three antiviral drugs against SARS-CoV-2 were studied extensively and initially available in Italy: remdesivir, molnupiravir, and nirmaltrelvir/ritonavir, but at present the latter is the only oral antiviral for SARS-CoV-2 available in Italy. Several real-world studies for the use of nirmatrelvir/ ritonavir in the Italian population have been published. Among the current unmet needs, a clear and universal definition for long COVID along with treatments and prevention are still lacking as is clarity of the pathogenetic mechanisms responsible for it.
H5N1 influenza A virus: lessons from past outbreaks and emerging threats
Galli Massimo,
Giacomelli Andrea,
Lai Alessia,
Zehender Gianguglielmo
The first highly pathogenic H5N1 emerged in 1959 on a chicken farm in Scotland. The ancestor of the strains presently circulating was isolated in 1996 from a domestic goose in China. Since 1997, more than 900 severe human infections have been reported. However, in nearly thirty years, H5N1 has failed to adapt to human-to-human transmission. At present the abundant circulation in various animal species, including mammals, increases the possibility of reassortments of new pandemic strains. Particularly alarming was the recent report of H5N1 infection among U.S. dairy cattle. A strong international effort from a global health perspective addressed to limit the avian strains circulation and to improve the preparedness for a new pandemic is urgently needed.
Original article
A mathematical model to estimate the probability of blood cultures positive for pyogenic streptococci
Leli Christian,
Bottino Paolo,
Ferrara Lidia,
Pizzo Valentina,
Canepari Monica,
Ciriello Maria Matilde,
Boverio Riccardo,
Rocchetti Andrea
Aims: The aim of this study was to assess the possible use of time to positivity (TTP) of blood cultures (BCs) collected at the Emergency Department (ED) to estimate the probability of pyogenic streptococci versus other Gram positive cocci in pairs and chains, such as Streptococcus pneumoniae, other viridans group streptococci or enterococci.
Methods: All patients 18 years of age or older evaluated at the ED from whom BCs were collected and were positive for Gram positive cocci in pairs and chains at the microscopic examination, were included in the study. The BCs included were collected by venipuncture, were mono-microbial and were the first bottles that flagged positive in each set. Complete blood count requested simultaneously with BCs along with medical history taken by the ED physician were also evaluated.
Results: In our case series, all BCs positive for Gram positive cocci in pairs or chains at microscopic examination with a TTP ≤6.3 hours were consistent with a pyogenic streptococcus (100% specificity; 95% CI: 92.7-100). Consequently, a TTP ≤6.3 hours has a 100% positive predictive value (95% CI: 30.9-100). Conversely, no pyogenic streptococci were recovered from positive BCs with a TTP >12.6 hours. Therefore, as screening test, it has 100% sensitivity (95% CI: 77-100) and 100% negative predictive value (95% CI: 83.4-100). The binomial logistic regression
model showed how as TTP increases, in BCs positive for Gram positive cocci in pairs and chains at the microscopic examination, the probability of a positive result for pyogenic streptococci decreases (odds ratio: 0.548; 95% confidence interval: 0.387-0.775; P=0.001).
Conclusions: The results of this study are an adjunctive tool to clinical aspects and fast microbiology laboratory tests to help assessing the likelihood of a positive blood culture for pyogenic streptococci.
Post-procedural fever after Transcatheter Aortic Valve Implantation (TAVI). A multi-centric study
Scheggi Valentina,
Bohbot Yohann,
Hasan Jasim,
Vanhaecke Pierre,
Del Pace Stefano,
Fumagalli Carlo,
Meucci Francesco,
Nardi Giulia,
Di Muro Francesca,
Menale Silvia,
Pisani Elena,
Vitiello Veronica,
Setti Valeria,
Zoppetti Nicola,
Valenti Renato,
Cerillo Alfredo,
Stefàno Pier Luigi,
Di Mario Carlo,
Rusinaru Dan,
Mirode Anfani,
Tribouilloy Christophe,
Marchionni Niccolò
Background: Fever following transcatheter aortic valve implantation (TAVI) poses a clinical challenge, necessitating a comprehensive diagnostic approach to discern between infectious and non-infectious origins. Despite its minimally invasive nature, TAVI disrupts protective anatomical barriers, leading to an increased risk of infection, as well as to aseptic inflammatory responses. Standardized strategies for the management of these patients are lacking.
Methods: We retrospectively analyzed 1074 consecutive patients. Data retrieved from electronic hospital charts included demographics, comorbidities, NYHA functional class, Multidimensional Prognostic Index (MPI), EUROSCORE II and STS risk score, pre- and post-procedural echocardiographic data, and procedural details. Fever was defined as temperature >37.5°C.
Results: Overall, 391 patients (36.4%) experienced at least one episode of fever, in all cases ensuing within the first 2 days after the procedure. Fever lasted only one day (ODF) in most patients (86%). Antibiotic prophylaxis varied, with cefazolin showing the highest efficacy. Management of post-TAVI fever was heterogeneous. Twenty-five percent of febrile patients received an empiric antibiotic therapy, although a presumed site of infection was identified in only 17% of them and just 19 patients (4.9%) had positive blood cultures. Of the 19 patients with positive cultures, 11 had a Gram+ and 8 a Gram- infection. Fever duration, invasive accesses, and clinical suspicion of infection influenced antibiotic initiation. Fever lasting more than one day (MODF) was associated with new-onset atrial fibrillation and prolonged in-hospital stay. Positive blood cultures were linked to higher mortality, especially with Gram- bacteremia. However, patients with short-term fever had a similar mortality to those without fever, highlighting the benign nature of self-limited fever.
Conclusions: Fever is a common complication after TAVI. A watchful waiting strategy is advisable in stable patients without evidence of infection and self-limited episodes of fever, while selected patients may benefit from an aggressive approach.
Scrub Typhus in Kerala: Demographic, Clinical, and Laboratory Predictors of ICU Admission in a Tertiary Care Setting
Saheed Shazia Zahara,
Goswami Debajyoti,
Niyas Vettakkara Kandy Muhammed,
Ananthanaryanan Rajalakshmi
Background: Scrub typhus, a mite-borne infection caused by Orientia tsutsugamushi, is endemic in South and Southeast Asia, including India. Although increasing awareness and improved healthcare access have reduced mortality, the disease remains a significant public health concern. Kerala, a southern Indian state, has reported scrub typhus cases for decades; however, comprehensive data on its clinical profile and severity indicators are limited. This study aimed to describe the clinical characteristics of scrub typhus and identify predictors of intensive care unit (ICU) admission.
Methods: A retrospective study was conducted on scrub typhus cases diagnosed at KIMSHEALTH, Thiruvananthapuram, India, from 2015 to 2021 using electronic medical records (EMR). Scrub typhus was defined as an acute febrile disease with positive IgM ELISA. Patients with other diagnoses explaining the febrile illness or those with incomplete data were excluded. Demographic characteristics, clinical features, laboratory findings, and patient outcomes were analyzed. ICU admission was the primary outcome. Binary logistic regression was used to identify independent predictors of ICU admission.
Results: A total of 241 patients were included in the study, of whom 74 (30.7%) required ICU admission. Most cases occurred between September and January, with a peak in December. The median age was 45 years (IQR: 24.5–60.5), and 122 (50.6%) were female. Fever lasting >7 days
was present in 46.1% of patients. Common symptoms included headache (38.2%), myalgia (37.3%), vomiting (31.5%), and breathlessness (19.5%). Hepatomegaly and splenomegaly were observed in 33.2% and 28.6% of cases, respectively, while eschar was noted in 20.3%. Most patients received doxycycline (82.6%), with some receiving azithromycin (7.1%) or both (10.4%).
In multivariable analysis using binary logistic regression, altered sensorium (adjusted odds ratio [aOR]: 6.63, 95% CI: 1.83–24.12, p=0.004) and breathlessness (aOR: 5.02, 95% CI: 2.31–10.90, p<0.001) were independent predictors of ICU admission.
Conclusions: Scrub typhus in Kerala exhibits seasonal variation, peaking from September to January. Breathlessness and altered sensorium present at admission were the strongest predictors of ICU admission The lower mortality in our study (2.1%) compared to national estimates may be attributed to improved healthcare access, early diagnosis, and prompt treatment. Further multicenter prospective studies are needed to validate these findings and improve risk stratification for severe disease.
Impact of Enterococcus infection in HSCT recipients: a national analysis
Sivasubramanian Barath Prashanth,
Antony Raj Ajay Sriram,
Ravikumar Diviya Bharathi,
Ravanam Aneela Satya,
Patel Rutvi Balkrishna,
Mudumalagurthy Samhitha,
Kotharu Devi Meghana,
Zeeshan Mohd,
Chavan Manisha,
Patel Jay,
Vala Akhila,
Tirupathi Raghavendra,
Dalal Rutul,
Shekar Saketh Palasamudram
Background: Enterococci are the third most common cause of healthcare-associated infections in the United States, affecting 10-12% of all transplant recipients worldwide. Enterococcal bacteremia complicates the post-transplant recovery and raises mortality to 18%. This study aims to identify factors linked to mortality in hematopoietic stem cell transplant (HSCT) recipients with Enterococcus infection.
Methods: We conducted a retrospective analysis using the National Inpatient Sample Database (2018-2021). Adults treated with HSCT and admitted for Enterococcus infection were identified using ICD-10 codes. The analysis utilized descriptive statistics and multivariate regression, with significance at a p-value ≤0.05.
Results: A total of 40,462 HSCT patients, 1.3% were admitted with Enterococcus infection. The crude mortality rate was higher in the Enterococcus cohort than in the non-Enterococcus cohort (10.4% vs. 4.6%); however, the mortality risk was substantially lower in the Enterococcus cohort (p<0.001). In the Enterococcus cohort, patients with fungal infections, sepsis, acute respiratory failure, and those with invasive ventilation had a high mortality risk (p<0.05). In leukemia patients treated with HSCT, the Enterococcus cohort had higher mortality than the non-Enterococcus cohort (12.5% vs. 5.0%; aOR 1.8, 95% CI 1.9-2.6, p=0.005).
Conclusions: In HSCT recipients, Enterococcus infection is a clinical marker for poor prognosis. Early broadspectrum antibiotic therapy is essential for patients with sepsis, respiratory compromise, and fungal co-infections. Additionally, a multidisciplinary team is crucial for managing respiratory and renal failure.
Case report
A new autochthonous case of amebiasis in Italy in a patient without risk factors: an alert for clinicians and laboratorians
Corich Lucia,
Bramuzzo Igor,
Perandin Francesca,
Treggiari Davide,
Scarso Salvatore,
Rigo Silvia,
Grosso Shamanta,
Diamante Paola,
Urbano Maria Teresa,
Crapis Massimo,
Basaglia Giancarlo,
Avolio Manuela
We describe a rare case of intestinal amebiasis of unknown source, in an immunocompetent patient with no risk factors. The detection of an autochthonous Entamoeba histolytica strain causing ulcerative colitis (UC) in a healthy individual was unexpected, but it was the second time it had occurred in Italy in a few months therefore, it highlighted the urgency to establish a new approach in the diagnosis of UC and more generally in the diagnosis of inflammatory bowel disease, involving routine parasitological investigation even in a non-endemic area.
Syphilitic pneumonia: case report and systematic review
Pipitone Giuseppe,
Abbott Michelle,
Gizzi Andrea,
Buscemi Calogero,
Guida Marascia Federica,
Imburgia Claudia,
Ciusa Giacomo,
La Sala Alba,
Mancuso Giuseppe Giorgio,
Messana Domenico,
Cascio Antonio,
Iaria Chiara
Syphilitic pneumonia is a rare secondary form of Treponema pallidum infection. In this article, we present a case of syphilitic pneumonia in a patient living with Human Immunodeficiency Virus (HIV) with good immune-virological status. We also performed a systematic review of literature and we found 43 cases of syphilitic pneumonia described since 1886. We added our case report and performed a statistical analysis. Our analysis showed that 40/44 (91%) were males, with a median age of 46 years old (IQR 37-56), 9/28 (32%) were people living with HIV (data not available for 16/44 patients), 17/27 (63%) had syphilitic-related hepatitis during the clinical presentation (data not available for 17/44 patients), and 28/42 (66.6%) of patients had maculopapular rash compatible with secondary forms (data not available for 2/42 patients). Furthermore, 74.4% of patients had nodular lesions on chest X-ray or pulmonary Computed Tomography scan. Given the high rate of nodular pneumonia among patients, clinicians should consider it as a common presentation in syphilitic pneumonia
Case of Granulicatella elegans endocarditis triggering both ischemic and haemorrhagic stroke. A rare clinical presentation from eastern India
Mondal Saikat,
Kottawar Venkatesh,
Parvin Sunitaj,
Das Munshi Boudhayan,
Banerjee Sourav,
Begam Nazneen Nahar,
Sengupta Mallika
We report a rare clinical presentation of a 54-year-old male diagnosed with infective endocarditis caused by Granulicatella elegans, a nutritionally variant streptococcus (NVS) characterized by unique growth requirements and high pathogenic potential. The patient presented with prolonged fever and residual hemiparesis following an ischemic stroke. Blood culture confirmed Granulicatella elegans, and imaging identified vegetations on a bicuspid aortic valve. Despite prompt antibiotic therapy, the course was complicated by acute intraventricular hemorrhage (IVH) and hydrocephalus, culminating in a fatal outcome. This report underscores the pathogenic challenges posed by Granulicatella elegans, highlights its catastrophic complications, and reviews its presentation and management in the context of existing literature and emphasizing the importance of prompt diagnosis, tailored antibiotic therapy, and vigilant monitoring.
The Infections in the History of Medicine
Not to lose control of war: narrative review of military louse control in the first half of XX Century
Simonetti Omar,
Martini Mariano,
Armocida Emanuele
Introduction: Insects and the diseases that they are capable to host have played a crucial role in the outcome of major military operations throughout recorded history. As a matter of fact, regular armies had to fight both against enemy uniform and invisible pathogens; the latter often causing battle casualties more disabling than bullets.
Methods: All the sources present on Pubmed and Google Scholar relating to the fight against Bartonella Quintana and Rickettsia prowazeki in the military field during the first and second world wars were studied, with particular attention to the articles published during the wars. The sources were then processed in a historical-medical perspective.
Results: First World War (WWI) was a position war also if considering the fight between humans against louse; with the latter being controlled by rudimentary but science-driven hygienic measures. Contrary, during Second World War (WWII) human forces, thanks to new research and development attainments, have gone on the counter-offensive by “shooting flights with cannons”.
Conclusions: The fascinating history of Bartonella Quintana and Rickettsia prowazekii tells us that the war against armies could mirror the war against infectious diseases and their arthropod vectors.
