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International Journal of Infectious... Jun 2024In hematology, prophylaxis for Pneumocystis jirovecii pneumonia (PCP) is recommended for patients undergoing hematopoietic stem cell transplantation and in selected...
A retrospective study of intravenous pentamidine for Pneumocystis jirovecii pneumonia prophylaxis in adult patients with hematologic malignancies-its utility during respiratory virus pandemics.
OBJECTIVES
In hematology, prophylaxis for Pneumocystis jirovecii pneumonia (PCP) is recommended for patients undergoing hematopoietic stem cell transplantation and in selected categories of intensive chemotherapy for hematologic malignancies. Trimethoprim-sulfamethoxazole (TMP-SMX) is the recommended first-line agent; however, its use is not straightforward. Inhaled pentamidine is the recommended second-line agent; however, aerosolized medications were discouraged during respiratory virus outbreaks, especially during the COVID-19 pandemic, in view of potential contamination risks. Intravenous (IV) pentamidine is a potential alternative agent. We evaluated the effectiveness and tolerability of IV pentamidine use for PCP prophylaxis in adult allogeneic hematopoietic stem cell transplantation recipients and patients with hematologic malignancies during COVID-19.
RESULTS
A total of 202 unique patients who received 239 courses of IV pentamidine, with a median of three doses received (1-29). The largest group of the patients (49.5%) who received IV pentamidine were undergoing or had received a hematopoietic stem cell transplant. The most common reason for not using TMP-SMX prophylaxis was cytopenia (34.7%). We have no patients who had breakthrough PCP infection while on IV pentamidine. None of the patients developed an infusion reaction or experienced adverse effects from IV pentamidine.
CONCLUSIONS
Pentamidine administered IV monthly is safe and effective.
Topics: Humans; Pentamidine; Pneumonia, Pneumocystis; Hematologic Neoplasms; Male; Retrospective Studies; Middle Aged; Female; Adult; Hematopoietic Stem Cell Transplantation; Aged; COVID-19; Pneumocystis carinii; Administration, Intravenous; Young Adult; SARS-CoV-2; Antifungal Agents; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 38615824
DOI: 10.1016/j.ijid.2024.107059 -
International Journal of Molecular... Apr 2024The mission of this review is to identify immune-damaging participants involved in antiviral immunoinflammatory lesions. We argue these could be targeted and their... (Review)
Review
The mission of this review is to identify immune-damaging participants involved in antiviral immunoinflammatory lesions. We argue these could be targeted and their activity changed selectively by maneuvers that, at the same time, may not diminish the impact of components that help resolve lesions. Ideally, we need to identify therapeutic approaches that can reverse ongoing lesions that lack unwanted side effects and are affordable to use. By understanding the delicate balance between immune responses that cause tissue damage and those that aid in resolution, novel strategies can be developed to target detrimental immune components while preserving the beneficial ones. Some strategies involve rebalancing the participation of immune components using various approaches, such as removing or blocking proinflammatory T cell products, expanding regulatory cells, restoring lost protective cell function, using monoclonal antibodies (moAb) to counteract inhibitory molecules, and exploiting metabolic differences between inflammatory and immuno-protective responses. These strategies can help reverse ongoing viral infections. We explain various approaches, from model studies and some clinical evidence, that achieve innate and adaptive immune rebalancing, offering insights into potential applications for controlling chronic viral-induced lesions.
Topics: Humans; Antibodies, Monoclonal; Pyrimethamine; Sulfadiazine
PubMed: 38612744
DOI: 10.3390/ijms25073935 -
Frontiers in Cellular and Infection... 2024Mendelian randomization (MR) analysis has been used in the exploration of the role of gut microbiota (GM) in type 2 diabetes mellitus (T2DM); however, it was limited to...
AIM
Mendelian randomization (MR) analysis has been used in the exploration of the role of gut microbiota (GM) in type 2 diabetes mellitus (T2DM); however, it was limited to the genus level. This study herein aims to investigate the relationship of GM, especially at the species level, with T2DM in order to provide some evidence for further exploration of more specific GM taxa and pathway abundance in T2DM.
METHODS
This two-sample MR study was based on the summary statistics of GM from the available genome-wide association study (GWAS) meta-analysis conducted by the MiBioGen consortium as well as the Dutch Microbiome Project (DMP), whereas the summary statistics of T2DM were obtained from the FinnGen consortium released data. Inverse variance weighted (IVW), MR-Egger, strength test (), and weighted median methods were used to examine the causal association between GM and the onset of T2DM. Cochran's statistics was employed to quantify the heterogeneity of instrumental variables. Bonferroni's correction was conducted to correct the bias of multiple testing. We also performed reverse causality analysis.
RESULTS
The corrected IVW estimates suggested the increased relative abundance of family (OR = 1.0704) and genus (OR = 1.0874), respectively, were associated with higher odds of T2DM, while that of species (OR = 0.9460) had a negative relationship with T2DM. The relationships of class , family , species , and species with T2DM were also significant according to the IVW results (all < 0.05).
CONCLUSIONS
GM had a potential causal association with T2DM, especially species , , and . Further studies are still needed to clarify certain results that are contradictory with previous findings.
Topics: Humans; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Microbiota; Sulfalene; Meta-Analysis as Topic
PubMed: 38596649
DOI: 10.3389/fcimb.2024.1327032 -
Veterinary Research Apr 2024Actinobacillus pleuropneumoniae (APP) is a bacterium frequently associated with porcine pleuropneumonia. The acute form of the disease is highly contagious and often...
Actinobacillus pleuropneumoniae (APP) is a bacterium frequently associated with porcine pleuropneumonia. The acute form of the disease is highly contagious and often fatal, resulting in significant economic losses for pig farmers. Serotype diversity and antimicrobial resistance (AMR) of APP strains circulating in north Italian farms from 2015 to 2022 were evaluated retrospectively to investigate APP epidemiology in the area. A total of 572 strains isolated from outbreaks occurring in 337 different swine farms were analysed. The majority of isolates belonged to serotypes 9/11 (39.2%) and 2 (28.1%) and serotype diversity increased during the study period, up to nine different serotypes isolated in 2022. The most common resistances were against tetracycline (53% of isolates) and ampicillin (33%), followed by enrofloxacin, florfenicol and trimethoprim/sulfamethoxazole (23% each). Multidrug resistance (MDR) was common, with a third of isolates showing resistance to more than three antimicrobial classes. Resistance to the different classes and MDR varied significantly depending on the serotype. In particular, the widespread serotype 9/11 was strongly associated with florfenicol and enrofloxacin resistance and showed the highest proportion of MDR isolates. Serotype 5, although less common, showed instead a concerning proportion of trimethoprim/sulfamethoxazole resistance. Our results highlight how the typing of circulating serotypes and the analysis of their antimicrobial susceptibility profile are crucial to effectively manage APP infection and improve antimicrobial stewardship.
Topics: Swine; Animals; Serogroup; Actinobacillus pleuropneumoniae; Microbial Sensitivity Tests; Enrofloxacin; Farms; Retrospective Studies; Pleuropneumonia; Anti-Bacterial Agents; Sulfamethoxazole; Trimethoprim; Italy; Swine Diseases; Actinobacillus Infections; Serotyping; Thiamphenicol
PubMed: 38594744
DOI: 10.1186/s13567-024-01305-x -
Journal of Environmental Management May 2024The extensive use of pharmaceuticals has raised growing concerns regarding their presence in surface waters. High concentrations of sulfamethoxazole (SMX) and lincomycin...
The extensive use of pharmaceuticals has raised growing concerns regarding their presence in surface waters. High concentrations of sulfamethoxazole (SMX) and lincomycin (LIN), as commonly prescribed antibiotics, persist in various wastewaters and surface waters, posing risks to public health and the environment. Biochar derived from accessible biowaste, like activated sludge biomass, offers a sustainable and eco-friendly solution to mitigate antibiotic release into water systems. This study investigates the effectiveness of HPO-modified activated sludge-based biochar (PBC) synthesized through microwave (MW) heating for the adsorption of SMX and LIN antibiotics. The synthesis parameters of PBC were optimized using a central composite design considering MW power, time, and HPO concentration. Characterization results validate the efficacy of the synthesis process creating a specific surface area of 365 m/g, and well-developed porosity with abundant oxygen-containing functional groups. Batch and dynamic adsorption experiments were piloted to assess the adsorption performance of PBC in single and binary antibiotic systems. Results show that PBC exhibits a higher affinity for SMX rather than LIN, with maximum adsorption capacities of 45.6 mg/g and 26.6 mg/g, respectively. Based on kinetic studies chemisorption is suggested as the primary mechanism for SMX and LIN removal. Equilibrium studies show a strong agreement with the Redlich-Peterson isotherm, suggesting a composite adsorption mechanism with a greater probability of multilayer adsorption for both antibiotics. Hydrogen bonding and π-π electron sharing are suggested as the prevailing adsorption mechanisms of SMX and LIN on the modified biochar. Furthermore, a dynamic adsorption system was replicated using a fixed bed column setup, demonstrating effective removal of SMX and LIN from pure water and real wastewater samples using PBC-loaded hydrogel beads (PBC-B). These findings serve as crucial support for upcoming studies concerning the realistic application of sludge-based biochar in the removal of antibiotics from water systems.
Topics: Lincomycin; Sulfamethoxazole; Charcoal; Adsorption; Sewage; Biomass; Water Pollutants, Chemical; Kinetics; Wastewater; Anti-Bacterial Agents
PubMed: 38593733
DOI: 10.1016/j.jenvman.2024.120742 -
BMC Infectious Diseases Apr 2024Nocardia farcinica is one of the most common Nocardia species causing human infections. It is an opportunistic pathogen that often infects people with compromised immune... (Review)
Review
BACKGROUND
Nocardia farcinica is one of the most common Nocardia species causing human infections. It is an opportunistic pathogen that often infects people with compromised immune systems. It could invade human body through respiratory tract or skin wounds, cause local infection, and affect other organs via hematogenous dissemination. However, N. farcinica-caused bacteremia is uncommon. In this study, we report a case of bacteremia caused by N. farcinica in China.
CASE PRESENTATION
An 80-year-old woman was admitted to Peking Union Medical College Hospital with recurrent fever, right abdominal pain for one and a half month, and right adrenal gland occupation. N. farcinica was identified as the causative pathogen using blood culture and plasma metagenomics next-generation sequencing (mNGS). The clinical considerations included bacteremia and adrenal gland abscess caused by Nocardia infection. As the patient was allergic to sulfanilamide, imipenem/cilastatin and linezolid were empirically administered. Unfortunately, the patient eventually died less than a month after the initiation of anti-infection treatment.
CONCLUSION
N. farcinica bacteremia is rare and its clinical manifestations are not specific. Its diagnosis depends on etiological examination, which can be confirmed using techniques such as Sanger sequencing and mNGS. In this report, we have reviewed cases of Nocardia bloodstream infection reported in the past decade, hoping to improve clinicians' understanding of Nocardia bloodstream infection and help in its early diagnosis and timely treatment.
Topics: Female; Humans; Aged, 80 and over; Nocardia; Nocardia Infections; Bacteremia; Sepsis
PubMed: 38589778
DOI: 10.1186/s12879-024-09230-2 -
Journal of Medicine and Life Dec 2023This study aimed to design, synthesize, and evaluate the cytotoxic activity of novel thiazole-sulfanilamide derivatives, specifically compounds M3, M4, and M5, through...
In silico study, synthesis, and antineoplastic evaluation of thiazole-based sulfonamide derivatives and their silver complexes with expected carbonic anhydrase inhibitory activity.
This study aimed to design, synthesize, and evaluate the cytotoxic activity of novel thiazole-sulfanilamide derivatives, specifically compounds M3, M4, and M5, through molecular docking and biological assays. The synthesis utilized essential chemical compounds, including sulfanilamide, chloro-acetyl chloride, thiourea, derivatives of benzaldehyde, and silver nitrate. The docking study was carried out using Molecular Operating Environment (MOE) software, and cytotoxic activity was predicted by MTT assay. The synthesized compounds demonstrated a reduction in the viability of cancer cells. Compound M5 had an IC50 of 18.53 µg/ml against MCF-7 cells, comparable to the IC50 of cisplatin. Additionally, compounds M3 and M4 had higher S scores than acetazolamide, indicating greater binding affinity to the active pocket of the receptor. Incorporating the thiazole ring in the synthesized compound augmented their flexibility and affinity for binding to the receptor. The inclusion of the metal complex additionally heightened the compounds' capacity to impede cellular growth.
Topics: Humans; Molecular Docking Simulation; Thiazoles; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Sulfonamides; Antineoplastic Agents; Sulfanilamides
PubMed: 38585528
DOI: 10.25122/jml-2023-0180 -
Clinical Microbiology and Infection :... Jul 2024Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Comparative efficacy and safety of Pneumocystis jirovecii pneumonia prophylaxis regimens for people living with HIV: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several regimens are available for the prophylaxis of PCP, including trimethoprim-sulfamethoxazole (TMP-SMX), dapsone-based regimens (DBRs), aerosolized pentamidine (AP), and atovaquone.
OBJECTIVES
To compare the efficacy and safety of PCP prophylaxis regimens in PWH by network meta-analysis.
METHODS
DATA SOURCES: Embase, MEDLINE, and CENTRAL from inception to June 21, 2023.
STUDY ELIGIBILITY CRITERIA
Comparative randomized controlled trials (RCTs).
PARTICIPANTS
PWH.
INTERVENTIONS
Regimens for PCP prophylaxis either compared head-to-head or versus no treatment/placebo.
ASSESSMENT OF RISK OF BIAS
Cochrane risk-of-bias tool for RCTs 2.
METHODS OF DATA SYNTHESIS
Title or abstract and full-text screening and data extraction were performed in duplicate by two independent reviewers. Data on PCP incidence, all-cause mortality, and discontinuation due to toxicity were pooled and ranked by network meta-analysis. Subgroup analyses of primary versus secondary prophylaxis, by year, and by dosage were performed.
RESULTS
A total of 26 RCTs, comprising 55 treatment arms involving 7516 PWH were included. For the prevention of PCP, TMP-SMX was ranked the most favourable agent and was superior to DBRs (risk ratio [RR] = 0.54; 95% CI, 0.36-0.83) and AP (RR = 0.53; 95% CI, 0.36-0.77). TMP-SMX was also the only agent with a mortality benefit compared with no treatment/placebo (RR = 0.79; 95% CI, 0.64-0.98). However, TMP-SMX was also ranked as the most toxic agent with a greater risk of discontinuation than DBRs (RR = 1.25; 95% CI, 1.01-1.54) and AP (7.20; 95% CI, 5.37-9.66). No significant differences in PCP prevention or mortality were detected among the other regimens. The findings remained consistent within subgroups.
CONCLUSIONS
TMP-SMX is the most effective agent for PCP prophylaxis in PWH and the only agent to confer a mortality benefit; consequently, it should continue to be recommended as the first-line agent. Further studies are necessary to determine the optimal dosing of TMP-SMX to maximize efficacy and minimize toxicity.
Topics: Humans; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Network Meta-Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Pneumocystis carinii; HIV Infections; AIDS-Related Opportunistic Infections; Dapsone; Pentamidine; Atovaquone; Antifungal Agents; Treatment Outcome
PubMed: 38583518
DOI: 10.1016/j.cmi.2024.03.037 -
Burns : Journal of the International... Aug 2024This study compared a novel topical hydrogel burn dressing (CI-PRJ012) to standard of care (silver sulfadiazine) and to untreated control in a swine thermal burn model,...
BACKGROUND
This study compared a novel topical hydrogel burn dressing (CI-PRJ012) to standard of care (silver sulfadiazine) and to untreated control in a swine thermal burn model, to assess for wound healing properties both in the presence and absence of concomitant bacterial inoculation.
METHODS
Eight equal burn wounds were created on six Yorkshire swine. Half the wounds were randomized to post-burn bacterial inoculation. Wounds were subsequently randomized to three treatments groups: no intervention, CI-PRJ012, or silver sulfadiazine cream. At study end, a blinded pathologist evaluated wounds for necrosis and bacterial colonization.
RESULTS
When comparing CI-PRJ012 and silver sulfadiazine cream to no treatment, both agents significantly reduced the amount of necrosis and bacteria at 7 days after wound creation (p < 0.01, independently for both). Further, CI-PRJ012 was found to be significantly better than silver sulfadiazine (p < 0.02) in reducing bacterial colonization. For wound necrosis, no significant difference was found between silver sulfadiazine cream and CI-PRJ012 (p = 0.33).
CONCLUSIONS
CI-PRJ012 decreases necrosis and bacterial colonization compared to no treatment in a swine model. CI-PRJ012 appeared to perform comparably to silver sulfadiazine. CI-PRJ012, which is easily removed with the application of room-temperature water, may provide clinical advantages over silver sulfadiazine.
Topics: Animals; Burns; Silver Sulfadiazine; Pilot Projects; Swine; Necrosis; Disease Models, Animal; Wound Healing; Anti-Bacterial Agents; Anti-Infective Agents, Local; Hydrogels; Bandages; Wound Infection; Random Allocation
PubMed: 38582695
DOI: 10.1016/j.burns.2024.03.018 -
Acta Crystallographica. Section C,... Apr 2024This report presents a comprehensive investigation into the synthesis and characterization of Schiff base compounds derived from benzenesulfonamide. The synthesis...
This report presents a comprehensive investigation into the synthesis and characterization of Schiff base compounds derived from benzenesulfonamide. The synthesis process, involved the reaction between N-cycloamino-2-sulfanilamide and various substituted o-salicylaldehydes, resulted in a set of compounds that were subjected to rigorous characterization using advanced spectral techniques, including H NMR, C NMR and FT-IR spectroscopy, and single-crystal X-ray diffraction. Furthermore, an in-depth assessment of the synthesized compounds was conducted through Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) analysis, in conjunction with docking studies, to elucidate their pharmacokinetic profiles and potential. Impressively, the ADMET analysis showcased encouraging drug-likeness properties of the newly synthesized Schiff bases. These computational findings were substantiated by molecular properties derived from density functional theory (DFT) calculations using the B3LYP/6-31G* method within the Jaguar Module of Schrödinger 2023-2 from Maestro (Schrodinger LLC, New York, USA). The exploration of frontier molecular orbitals (HOMO and LUMO) enabled the computation of global reactivity descriptors (GRDs), encompassing charge separation (E) and global softness (S). Notably, within this analysis, one Schiff base, namely, 4-bromo-2-{N-[2-(pyrrolidine-1-sulfonyl)phenyl]carboximidoyl}phenol, 20, emerged with the smallest charge separation (ΔE = 3.5780 eV), signifying heightened potential for biological properties. Conversely, 4-bromo-2-{N-[2-(piperidine-1-sulfonyl)phenyl]carboximidoyl}phenol, 17, exhibited the largest charge separation (ΔE = 4.9242 eV), implying a relatively lower propensity for biological activity. Moreover, the synthesized Schiff bases displayed remarkeable inhibition of tankyrase poly(ADP-ribose) polymerase enzymes, integral in colon cancer, surpassing the efficacy of a standard drug used for the same purpose. Additionally, their bioavailability scores aligned closely with established medications such as trifluridine and 5-fluorouracil. The exploration of molecular electrostatic potential through colour mapping delved into the electronic behaviour and reactivity tendencies intrinsic to this diverse range of molecules.
Topics: Humans; Schiff Bases; Models, Molecular; Molecular Conformation; Crystallography, X-Ray; Spectroscopy, Fourier Transform Infrared; Hydrogen Bonding; Colonic Neoplasms; Phenols
PubMed: 38577890
DOI: 10.1107/S205322962400233X