An overview of sulbactam-durlobactam approval and implications in advancing therapeutics for hospital-acquired and ventilator-associated pneumonia by acinetobacter baumannii-calcoaceticus complex: A narrative review.

Purpose: Infections caused by Acinetobacter baumannii, particularly those resistant to antibiotics such as carbapenem, have become a global health crisis with a significant mortality rate. Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) resulting from the A. baumannii-calcoaceticus (ABC) complex represent a major clinical challenge. This review aimed to understand the approval process, mechanism of action, therapeutic potential, and future implications of sulbactam-durlobactam therapy (SUL-DUR). Methods: PubMed, Web of Science, EMBASE, Clinical trials. gov, ICTRP, and CENTRAL were searched for studies on SUL-DUR for the treatment of hospital-acquired pneumonia and ventilator-associated pneumonia. Also, World Health Organization, U.S. Food and Drug Administration, and Centers for Disease Control and Prevention websites were searched for relevant information. Results: SUL-DUR, marketed as Xacduro, is a novel pharmaceutical combination that functions as a narrow-spectrum parenterally administered antibiotic. Sulbactam acts as a ß-lactamase inhibitor, whereas durlobactam protects against degradation by A. baumannii enzymes. A phase 1 trial successfully established the safety and tolerability of SUL-DUR in patients with normal and mild renal impairment. A phase 2 trial demonstrated the safety and tolerability of SUL-DUR in a larger population with urinary tract infections. A phase 3 trial showed that SUL-DUR was non-inferior to colistin in terms of mortality in A. baumannii-related VAP, HAP, and bacteremia. Conclusion: The combination of sulbactam and durlobactam is a promising treatment option for HAP and VAP caused by ABC complex.

Prevalence of hepatitis B and C infections among HIV-positive men who have sex with men: A systematic review and meta-analysis.

Background: Human immunodeficiency virus (HIV) infection is highly prevalent and often coexists with other infectious diseases, especially Hepatitis B virus (HBV) and Hepatitis C virus (HCV). Men who have sex with men (MSM) represent a vulnerable population in terms of HIV infection. We aimed to determine the prevalence of HCV, HBV among HIV-infected MSM. Methods: This systematic review and meta-analysis searched PubMed, Cochrane, Scopus, Web of Science, and ProQuest up-to 2023/04/22. All studies reporting the prevalence of HBV or HCV infection in MSM PLHIV were included. Meta-analysis used random effect model for synthesis and I 2 along with prediction interval for heterogeneity. Subgroup analysis based on continent and meta-regression for study size, average age and year of publication were used to explore heterogeneity. Modified Newcastle-Ottawa Scale was used to evaluate the quality of studies according to the protocol (PROSPERO: CRD42023428764). Results: Fifty-six of 5948 studies are included. In 53 studies with 3,07,589 participants, a pooled prevalence of 7% (95% confidence interval [CI]: 5-10) was found for HCV among MSM PLHIV, while a 9% (95% CI: 4-18) prevalence was found for HBV infection from five studies which included 5641 MSM PLHIV. Asia reported the lowest pooled prevalence at 5.84% (95% CI: 2.98-11.13) for HCV while Europe reported the highest pooled prevalence at 7.76% (95% CI: 4.35-13.45). Baujat plot and influence diagnostic identified contributors to influence and between-study heterogeneity. Sensitivity analyses omitting these studies result in considerably more precise estimates. Another sensitivity analysis as leave-one-out meta-analysis did not change any pooled estimate significantly. Conclusion: There is a significant burden of HCV and HBV among MSM PLHIV worldwide, with varying prevalence rates. Future studies should focus on these multimorbidity clusters and investigate factors influencing disease burden, long-term outcomes, optimal testing strategies, and tailored interventions.

Estimation of the Parasitic Burden of Soil-Transmitted Helminths Among Pregnant Women in the Maharashtra State of India Using qPCR: A Community-Based Study.

Background: Soil-transmitted helminth (STH) infections are widespread in developing countries with inadequate sanitation facilities. These infections can lead to malnutrition, anemia, and other complications that can negatively impact both the mother's and fetus's health during pregnancy. This study aimed to estimate the burden of STH by Kato-Katz microscopy and quantitative polymerase chain reaction (qPCR) in pregnant women from rural India. The diagnostic accuracy of these two methods was also compared. Material and Methods: A community-based cross-sectional study was conducted in rural areas of Wardha district of Maharashtra state. We randomly selected and interviewed 688 pregnant women. A total of 534 (77.61%) participants gave stool samples. Two containers (60 mL) labeled with a unique identification number were given to pregnant women to collect stool samples for Kato-Katz microscopy and qPCR. Stool specimens were transported to an accredited lab and examined within 24 hours. Suitable examinations were conducted to compare sensitivity between two tests. Results: The results are presented for 534 participants who gave stool samples. The prevalence of any STH by Kato-Katz stool microscopy was 6.55% (95%CI 4.46-12.19), and that by qPCR was 20.41 (95%CI 17.53-29.40). The sensitivity of Kato-Katz microscopy was 29.17% compared to sensitivity of 90.83% by qPCR (P = 0.001). Pregnant women with STH infection have a significantly lower weight gain during pregnancy, and the majority were either mild or moderate anemic compared to those without STH. Conclusion: The study highlighted significant differences in prevalence of STH among pregnant women by Kato-Katz microscopy and qPCR. The sensitivity of qPCR for detecting STH was higher than that of Kato-Katz microscopy.

Prevalence, types, risk factors, and outcomes of cardiorenal syndrome in a rural population of central India: A cross-sectional study.

BACKGROUND AND OBJECTIVES: Heart failure leading to renal dysfunction and vice-versa termed as Cardio-Renal Syndrome(CRS) has now been increasingly identified as a marker of higher morbidity and mortality. Till date, there is limited data available regarding clinical profile, associated risk factors and outcome of CRS in rural population of central India. This study was conducted to elucidate the prevalence, risk factors, and outcome of CRS and its types. METHODS: This was a single-centric, cross-sectional study conducted amongst the patients admitted to medicine wards and ICCU from October 2017 to September 2019. Classification given by RONCO et al. in 2008 was used for classifying CRS patients into various types. Cross-sectional data was used to find the prevalence, risk factors and their inter-relationship with outcome and mortality. STATA software was used for statistical analysis. RESULTS: Out of 96 CRS patients, 47(48.96%) were Type 1, 22 (22.92%) were type 2, 19(19.79%) were type 4 and 3 (3.13% ) were type 3, and 5 (5.21%) were of type 5. Most common risk factor was Hypertension (HTN) found in 46 (47.92%), followed closely by Coronary Artery Disease (CAD) and anaemia. Mortality was seen in 44(45.83%) of CRS patients and it was significantly high. High mortality was common in patients of types 3 and type 5 CRS. Risk factors like HTN, CAD, smoking, reduced glomerular filtration rate, low ejection fraction and sepsis were significantly associated with worse outcomes across all CRS sub-types. INTERPRETATION AND CONCLUSIONS: There is high mortality among CRS. Prevention or optimal management of HTN, CAD and sepsis is required to decrease mortality. There is need for more population based studies for confirming our study findings.

Interrelation of Glycemic Status and Neuropsychiatric Disturbances in Farmers with Organophosphorus Pesticide Toxicity.

BACKGROUND: Diverse group of agro-chemicals are indiscriminately sprayed by the farmers for pest control to enhance crop yield. About 25 million agricultural workers in the developing world suffer from at least one episode of poisoning each year, mainly by anticholinesterase- like organophosphates (OPs). OBJECTIVE: The present study was aimed to establish the OP toxicity in 187 occupationally exposed pesticide sprayers of mango plantation in rural Malihabad, Lucknow, in terms of neuro-cognitive impairment, mental health status, clinical symptoms, diabetes, and hematological factors. METHOD: The exposed group was compared to 187 pesticides-unexposed normal healthy persons engaged in normal usual agricultural work (age, sex and education corresponding to age group of selected subject group) from Rural Malihabad, Lucknow (India). Neuro-cognitive impairment was measured using the Subjective Neurocognition Inventory and mental health status using the General Health questionnaire-28. The subjects were also tested for biochemical and enzymatic parameters. RESULTS: The exposed farmers showed alterations in enzymatic and clinical parameters. While the rates of anxiety / insomnia and severe depression were also significantly higher in the pesticide sprayers, disorders affecting psychomotor speed, selective attention, divided attention, verbal memory, nonverbal memory, prospective memory, spatial functioning, and initiative/energy were all lower in the sprayers. Pesticide sprayers showed a number of clinical symptoms like eczema, saliva secretion, fatigue, headache, sweating, abdominal pain, nausea, superior distal muscle weakness, inferior distal muscle weakness, hand tingling and etc. which all significantly correlated with the number of working years. CONCLUSION: These findings suggested that farmers who work with OPs are prone to neuro-psychological disorders and diabetes.

The influence of organophosphate and carbamate on sperm chromatin and reproductive hormones among pesticide sprayers.

This study is aimed at evaluating the association between occupational exposure to organophosphate (OP) and carbamate (CB) pesticides and semen quality as well as levels of reproductive and thyroid hormones of pesticide sprayers in Malihabad, Lucknow, Uttar Pradesh, India. Thirty-five healthy men (unexposed group) and 64 male pesticide sprayers (exposed group) were recruited for clinical evaluation of fertility status. Fresh semen samples were evaluated for sperm quality and analyzed for DNA fragmentation index (DFI) by flow cytometry. Pesticide exposure was assessed by measuring erythrocyte acetylcholinesterase and plasma butyrylcholinesterase (BuChE) with a Test-mate ChE field kit. Serum levels of total testosterone (Tt), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) were analyzed using enzyme immunoassay kits. Evidence of pesticide exposure was found in 88.5% of sprayers and significant increments were observed in sperm DFI with significant decrease in some semen parameters. DFI was negatively correlated with BuChE, sperm concentration, morphology, and vitality in these pesticide sprayers. The levels of Tt, PRL, FT4, and TSH appeared to be normal; however, there was a tendency for increased LH and FSH levels in exposed workers. The results confirm the potential impact of chronic occupational exposure to OP and CB pesticides on male reproductive function, which may cause damage to sperm chromatin, decrease semen quality, and produce alterations in reproductive hormones, leading to adverse reproductive health outcomes.

Biochemical and immunological parameters as indicators of osteoarthritis subjects: role of OH-collagen in auto-antibodies generation.

Osteoarthritis (OA) is characterized by inflammation of the knee joint, which is caused by accumulation of cytokines and C-reactive protein (CRP) in the extracellular matrix as an early immune response to infection. The articular cartilage destruction is discernible by elevated tumour necrosis factor-α (TNF-α). In this study, blood samples of knee osteoarthritis patients were analyzed for biochemical and physiological parameters based on the lipid profile, uric acid, total leukocyte count (TLC), hemoglobin percentage (Hb%) and absolute lymphocyte count (ALC). Furthermore, immunological parameters including TNF-α , interleukin-6 (IL-6) and CRP were analyzed. The presence of antibodies against hydroxyl radical modified collagen-II ((•)OH-collagen-II) was also investigated in arthritis patients using direct binding ELISA. The uric acid and lipid profiles changed extensively. Specifically, increased uric acid levels were associated with OA in both genders, as were enhanced immunological parameters. The TNF-α level also increased in both genders suffering from OA. Finally, auto-antibodies against OH-collagen II antigen were found in the sera of arthritis patients. These results indicated that immunological parameters are better predictors or indexes for diagnosis of OA than biochemical parameters.

Bioelectricity from kitchen and bamboo waste in a microbial fuel cell.

This study evaluated bioelectricity generation by using kitchen garbage (KG) and bamboo waste (BW) as a solid waste management option by a microbial fuel cell (MFC) method. The nutrient content [nitrogen, phosphorus and potassium (NPK)] of the by-products of bioelectricity were also analyzed and assessed for their potential use as a soil amendment. A one-chamber MFC was used for bioelectricity generation in laboratory experiments using both KG and BW. A data-logger recorded voltage every 20 mins at a constant room temperature of 25°C over 45 days. The trend of voltage generation was different for the two organic wastes. In the case of KG, the voltage at the initial stage (0-5 days) increased rapidly and then gradually to a peak of 620 mV. In contrast, the voltage increased gradually to a peak of 540 mV in the case of BW. The by-products of bioelectricity can be used as soil conditioner as its NPK content was in the range of soil conditioner mentioned in other literature. Thus, the MFC has emerged as an efficient and eco-friendly solution for organic waste management, especially in developing and technologically less sophisticated countries, and can provide green and safe electricity from organic waste.

Phosphorus retention in a mesotrophic lake under transient loading conditions: insights from a sediment phosphorus binding form study.

Phosphorus retention in sediments has been estimated for three basins in Lake Simcoe, a mesotrophic lake in Ontario, Canada. Total phosphorous (TP) fractionation was used to examine the concentration of phosphorus (P) binding forms in the sediments of Cook's Bay, Kempenfelt Bay, and the Main Basin. The extended sequential extractions allowed us to differentiate between organic-, inorganic-, carbonate-bounded and redox-sensitive phosphorus. Our results showed different mechanisms of P release in each of the three investigated basins, which may be linked to their distinct loading histories, present land-uses and morphology of the sampling sites. In the deep Main Basin, where moderate changes in P loading have been induced by deforestation, sediments are not an important long-term source of diagenetically mobile P, as almost 75% of P is released within a short time scale. P release is predominantly generated by a continuous epilimnetic P flux, rather than a large inventory of temporary P stored in the sediments. Diagenesis in the upper sediment layers is fast enough to prevent a large accumulation of temporary P. In the much deeper glacially formed Kempenfelt Bay with a highly urbanized catchment, P release from the sediments is dominated by the redox-sensitive P fraction, representing up to 40% and 57% of long- and short-term sediment P release, respectively. In the shallow and agriculturally-impacted Cook's Bay, the main P binding form that can be mobilized through diagenesis is carbonate-bound P. This fraction contributes 40.1% and 37.6% to the long- and short-term P sediment release, respectively. Although different mechanisms of P release have been revealed for the three basins in Lake Simcoe, the vertical profiles indicate that the sediments throughout the system are still able to bind deposited P.

Arsenic bioaccessibility in a soil amended with drinking-water treatment residuals in the presence of phosphorus fertilizer.

A laboratory incubation study was conducted to determine the effect of drinking-water treatment residuals (WTRs) on arsenic (As) bioaccessibility and phytoavailability in a poorly As-sorbing soil contaminated with arsenical pesticides and fertilized with triple super phosphate (TSP). The Immokalee soil (a sandy spodosol with minimal As-retention capacity) was amended with 2 WTRs (Al and Fe) at 5 application rates ranging between 0% and 5% wt/wt. Sodium arsenate and TSP were used to spike the soil with 90 mg As kg(-1) and 115 mg P kg(-1), respectively. Bioaccessible As was determined at time 0 (immediately after spiking), and at 6 and 12 months of equilibration using an in vitro gastrointestinal test, and As phytoavailability was measured with a 1-M KC1 extraction test. Arsenic phytoavailability decreased immediately after spiking (20% availability at 5% rate), but only after 6 months for the Al-WTR- and the Fe-WTR-amended soil, respectively. Arsenic bioaccessibility simulated for the stomach and intestine phases showed that the Fe-WTR was more effective than the Al-WTR in resisting the harsh acidic conditions of the human stomach, thus preventing As release. Both the phytoavailable As and the bioaccessible As were significantly correlated (p < 0.001) for soil spiked with either Al- or Fe-WTR. Both WTRs were able to decrease soil As bioaccessibility irrespective of the presence or absence of P, which was added as TSP. Results indicate the potential of WTRs in immobilizing As in contaminated soils fertilized with P, thereby minimizing soil As bioaccessibility and phytoavailability.

Urinary iodine levels in three ecological zones of Bangladesh.

Urinary iodine levels in children (5-11 years) and in adult males and females (15-44 years) of three ecological zones (hilly, flood-prone and plains) of Bangladesh were analyzed to determine the status of biochemical iodine deficiency in the country. Data indicated that a large majority of the population all over Bangladesh have biochemical iodine deficiency urinary iodine excretion (UIE) less than the accepted cut-off level of 10 µg/dl. Adults were deficient to comparable degrees, 31.3% severely iodine deficient. The flood-prone zone was less affected: 71.7% children had iodine deficiency and 25% were severely deficient. Adults of this zone were less affected than the children. Iodine deficiency was least severe in the plain zone: 59.8% children were biochemically iodine deficient and of them 23.4% had UIE less than 2.0 µg/dl. In the case of the adults of this zone, 60.8% were biochemically iodine deficient and 20.6% had severe iodine deficiency. The results indicate that Bangladesh as a whole is an iodine deficient region, with the hilly zone being the most severely affected. Children were slightly more affected than the adults, and females were more affected than the males.