Mechanism of action, resistance, interaction, pharmacokinetics, pharmacodynamics, and safety of fostemsavir.

The Food and Drug Administration (FDA) has licensed many antiretroviral medications to treat human immunodeficiency virus type 1 (HIV-1), however, treatment options for people with multi-drug resistant HIV remain limited. Medication resistance, undesirable effects, prior tolerance, and previous interlacement incapacity to deliver new drug classes all lead to the requirement for new medication classes and drug combination therapy. Fostemsavir (FTR) is a new CD-4 attachment inhibitor medicine that was recently authorized by the United States FDA to treat HIV-1. In individuals with multidrug-resistant (MDR) HIV-1, FTR is well tolerated and virologically active. According to recent investigations, drug combination therapy can positively affect MDR-HIV. The mechanism of action, resistance, interaction, pharmacokinetics, pharmacodynamics, and safety of FTR has been highlighted in this review.

Molecular evaluation of aminoglycosides resistance and biofilm formation in Klebsiella pneumoniae clinical isolates: A cross-sectional study.

Background and Aims: Resistance to antibiotics and the capability to develop biofilm as two main virulent determinants of Klebsiella pneumoniae have important role in infection persistence. The aim of the study was to evaluate the association between the prevalence of aminoglycoside resistance and virulence genes and biofilm formation capacity in K. pneumoniae strains isolated from hospitalized patients in South-West of Iran. Methods: A total of 114 non-duplicate clinical isolates of K. pneumoniae collected from Ahvaz teaching hospitals. Identification of species was performed by biochemical tests and then confirmed by polymerase chain reaction (PCR) of rpoB gene. The susceptibility to antibiotics was determined by Kirby-Bauer disk diffusion method. Biofilm formation was assessed by microtiter plate method. Finally, PCR was conducted to detect virulence gene determinants including fimbrial genes, aminoglycoside modifying enzymes- and 16S rRNA methylase (RMTase) genes. Results: Totally, all collected strains were carbapenem resistant and showed multidrug- and extensively drug-resistance phenotype (75% and 25%, respectively). Seventy-one percent (n = 81) of isolates were non-susceptible to aminoglycosides. Among aminoglycoside antibiotics, K. pneumoniae isolates showed the highest and lowest resistance rates to tobramycin (71%) and the amikacin (25%), respectively. All biofilm producer strains were positive for the presence virulence determinants including ecpA, fimA, mrkD, and mrkA. Of 81 aminoglycosides non-susceptible isolates 33% were positive for the presence ant (2″)-Ia as the most prevalent gene followed by aac (3')-IIa and armA (27%), aac (6')-Ib (18%), and aph (3')-Ia (15%). Conclusion: K. pneumoniae isolates showed the highest and the lowest aminoglycoside resistance rates to tobramycin and amikacin, respectively. Majority of isolates were biofilm producers and there was significant association between antibiotic resistance pattern and the strength of biofilm production. The ant(2″)-Ia, aac (3')-IIa, and armA genes in aminoglycoside-resistant isolates.

The biofilm formation and antibiotic resistance of bacterial profile from endotracheal tube of patients admitted to intensive care unit in southwest of Iran.

Ventilator-associated pneumonia (VAP) is a prevalent nosocomial illness in mechanically ventilated patients. Hence, the aim of this study was to investigate the pattern of antibiotic resistance and biofilm formation of bacterial profiles from Endotracheal Tubes of patients hospitalized in an intensive care unit in southwest Iran. According to the standard operating method, the microbiological laboratory conducts bacteria culture and susceptibility testing on endotracheal Tube samples suspected of carrying a bacterial infection. The Clinical and laboratory standards institute (CLSI) techniques are used to determine the Antimicrobial resistance (AMR) of bacterial isolates to antibiotics using the disk diffusion method. The crystal violet staining method was used to assess the biofilm-forming potential of isolates in a 96-well microtiter plate. In total, (51%) GPBs were included in this study. The isolated GPB were coagulase-negative Staphylococcus (16%), S. aureus (14%). In total, (40%) of GNB were included in this study. The isolated GNB were Klebsiella spp. (36%), A. baumannii (22%), P. aeruginosa (35%). (32%) bacterial strains were MDR and (29%) strains were XDR. The results of biofilm formation showed (72%) were biofilm producers. VAP is a common and severe nosocomial infection in mechanically ventilated patients. Controlling biofilm formation, whether on the ET or in the oropharyngeal cavity, is thus an important technique for treating VAP. Colistin and linezolid are antibiotics that are effective against practically all resistant GNB and GPB isolates.

A Comprehensive Review of the Protein Subunit Vaccines Against COVID-19.

Two years after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), in December 2019, the first infections were identified in Wuhan city of China. SARS-CoV-2 infection caused a global pandemic and accordingly, 5.41 million deaths worldwide. Hence, developing a safe and efficient vaccine for coronavirus disease 2019 (COVID-19) seems to be an urgent need. Attempts to produce efficient vaccines inexhaustibly are ongoing. At present time, according to the COVID-19 vaccine tracker and landscape provided by World Health Organization (WHO), there are 161 vaccine candidates in different clinical phases all over the world. In between, protein subunit vaccines are types of vaccines that contain a viral protein like spike protein or its segment as the antigen assumed to elicit humoral and cellular immunity and good protective effects. Previously, this technology of vaccine manufacturing was used in a recombinant influenza vaccine (RIV4). In the present work, we review protein subunit vaccines passing their phase 3 and 4 clinical trials, population participated in these trials, vaccines manufactures, vaccines efficiency and their side effects, and other features of these vaccines.

Mechanism of action, resistance, synergism, and clinical implications of azithromycin.

BACKGROUND: Azithromycin (AZM), sold under the name Zithromax, is classified as a macrolide. It has many benefits due to its immunomodulatory, anti-inflammatory, and antibacterial effects. This review aims to study different clinical and biochemisterial aspects and properties of this drug which has a priority based on literature published worldwide. METHODS: Several databases including Web of Science, Google Scholar, PubMed, and Scopus were searched to obtain the relevant studies. RESULTS: AZM mechanism of action including the inhibition of bacterial protein synthesis, inhibition of proinflammatory cytokine production, inhibition of neutrophil infestation, and macrophage polarization alteration, gives it the ability to act against a wide range of microorganisms. Resistant organisms are spreading and being developed because of the irrational use of the drug in the case of dose and duration. AZM shows synergistic effects with other drugs against a variety of organisms. This macrolide is considered a valuable antimicrobial agent because of its use as a treatment for a vast range of diseases such as asthma, bronchiolitis, COPD, cystic fibrosis, enteric infections, STIs, and periodontal infections. CONCLUSIONS: Our study shows an increasing global prevalence of AZM resistance. Thus, synergistic combinations are recommended to treat different pathogens. Moreover, continuous monitoring of AZM resistance by registry centers and the development of more rapid diagnostic assays are urgently needed.

Bedaquiline: Current status and future perspectives.

The development of drug-resistant tuberculosis (TB) is a major threat worldwide. Based on World Health Organization (WHO) reports, it is estimated that more than 500 000 new cases of drug-resistant TB occur annually. In addition, there are alarming reports of increasing multidrug-resistant TB (MDR-TB) and the emergence of extensively drug-resistant TB (XDR-TB) from different countries of the world. Therefore, new options for TB therapy are required. Bedaquiline (BDQ), a novel anti-TB drug, has significant minimum inhibitory concentrations (MICs) both against drug-susceptible and drug-resistant TB. Moreover, BDQ was recently approved for therapy of MDR-TB. The current narrative review summarises the available data on BDQ resistance, describes its antimicrobial properties, and provides new perspectives on clinical use of this novel anti-TB agent.

A review on mechanism of action, resistance, synergism, and clinical implications of mupirocin against Staphylococcus aureus.

Mupirocin (MUP), bactroban, or pseudomonic acid is a natural crotonic acid derivative drug extracted from Pseudomonas fluorescens which is produced by modular polyketide synthases. This antibiotic has a unique chemical structure and mechanism of action. It is a mixture of A-D pseudomonic acids and inhibits protein synthesis through binding to bacterial isoleucyl-tRNA synthetase. MUP is often prescribed to prevent skin and soft tissue infections caused by S. aureus isolates and where the MRSA isolates are epidemic, MUP may be used as a choice drug for nasal decolonization. It is also used for prevention of recurring infections and control the outbreaks. The emergence of MUP resistance has been increasing particularly among methicillin-resistant Staphylococcus aureus (MRSA) isolates in many parts of the world and such resistance is often related with MUP widespread uses. Although both low-level and high-level MUP resistance were reported among MRSA isolates, the rate of resistance is different in various geographic areas. In this review, we will report the global prevalence of MUP resistance, discuss synergism and mechanism of action of MUP, and provide new insights into the clinical use of this antibiotic.

The frequency of class1 and 2 integrons in Pseudomonas aeruginosa strains isolated from burn patients in a burn center of Ahvaz, Iran.

BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen with the ability to cause severe nosocomial infections and remains a major problem in burn patients. This organism shows a remarkable antimicrobial resistance and is often resistant to multiple antibiotics. Integron genes as mobile genetic elements are playing an important role in the spread of P. aeruginosa antibiotic resistance. This study was aimed to investigate the occurrence of class 1, and 2 integron genes (int1, int2), among P. aeruginosa strains isolated from patients with burn infections. METHODS: In total 93 clinical isolates of P. aeruginosa were screened. The antimicrobial susceptibilities of 9 common antimicrobial agents were tested against the isolates using disk diffusion method. PCR amplification was performed on extracted DNAs for the detection of int1, and int2 genes using the set of specific primers. RESULTS: The majority of P. aeruginosa isolates were from wound infection (69.9%). In disk diffusion method, most isolates showed remarkable resistance to tested antibiotics with highest against gentamicin (94.62%) and ciprofloxacin (93.55%). PCR amplification revealed that 89(95.7%) of P. aeruginosa strains carried int1, but none of them harbored int2 genes. The distribution of int1 gene was highest in blood (100%), followed by wound isolates (95.38%). CONCLUSIONS: We demonstrated a high antimicrobial resistance among P. aeruginosa isolates in our setting. int1 was prevalent and seems to play an important role in multidrug resistance among the isolates. So, performance of antibiotic surveillance programs is necessary for choosing the appropriate therapy and management of infection control practices.