Nitazoxanide is a new thiazolide antiparasitic agent that shows excellent in vitro activity against a wide variety of protozoa and helminths. It is given by the oral route with good bioavailability and is well tolerated, with primarily mild gastrointestinal side effects. At present, there are no documented drug-drug interactions. Nitazoxanide has been licensed for the treatment of Giardia intestinalis-induced diarrhea in patients >or=1 year of age and Cryptosporidum-induced diarrhea in children aged 1-11 years. At present, it is pending licensure for treatment of infection due to Cryptosporidium species in adults and for use in treating immunocompromised hosts. It represents an important addition to the antiparasitic arsenal.

Background COVID-19 is a pandemic disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Predictors for severe COVID-19 infection have not been well defined. Determination of risk factors for severe infection would enable identifying patients who may benefit from aggressive supportive care and early intervention. Methods We conducted a retrospective observational study of 197 patients with confirmed COVID-19 admitted to a tertiary academic medical center. Results Of 197 hospitalized patients, the mean (SD) age of the cohort was 60.6 (16.2) years, 103 (52.3%) were male, and 156 (82.1%) were black. Severe COVID-19 infection was noted in 74 (37.6%) patients, requiring intubation. Patients aged above 60 were significantly more likely to have severe infection. Patients with severe infection were significantly more likely to have diabetes, renal disease, and chronic pulmonary disease and had significantly higher white blood cell counts, lower lymphocyte counts, and increased C-reactive protein (CRP) than patients with nonsevere infection. In multivariable logistic regression analysis, risk factors for severe infection included pre-existing renal disease (odds ratio [OR], 7.4; 95% CI, 2.5–22.0), oxygen requirement at hospitalization (OR, 2.9; 95% CI, 1.3–6.7), acute renal injury (OR, 2.7; 95% CI, 1.3–5.6), and CRP on admission (OR, 1.006; 95% CI, 1.001–1.01). Race, age, and socioeconomic status were not independent predictors. Conclusions Acute or pre-existing renal disease, supplemental oxygen upon hospitalization, and admission CRP were independent predictors for the development of severe COVID-19. Every 1-unit increase in CRP increased the risk of severe disease by 0.06%.

Vancomycin is superior to TMP-SMZ in efficacy and safety when treating intravenous drug users who have staphylococcal infections. However, all treatment failures occurred in patients with MSSA infection at any site. Therefore, TMP-SMZ may be considered as an alternative to vancomycin in selected cases of MRSA infection.

At a crucial time with rapid spread of Omicron SARS-CoV-2 virus variant globally, the United States Food and Drug Administration has issued an emergency use authorization for two oral antivirals molnupiravir (>18 years) and nirmatrelvir-ritonavir (Paxlovid) (≥12 years; >40kg ) for the outpatient treatment of mild to moderate COVID–19 patients who are at risk for progression. Molnupiravir is a nucleoside analogue, whereas nirmatrelvir is a SARS-CoV-2 main protease inhibitor, and ritonavir is an HIV-1 protease inhibitor. Drug interactions are a major concern for nirmatrelvir-ritonavir. Nirmatrelvir-ritonavir demonstrated a greater risk reduction in hospitalization and death than molnupiravir compared to placebo. Both drugs need to be started within five days of symptoms onset and given for five days duration. This article will review the two oral COVID-19 antiviral drugs including the mechanisms of action, antiviral activity, pharmacokinetics, drug interactions, clinical experience including trials, adverse events, recommended indications, and formulary considerations.

Over a 19-month period, 165 patients with 183 infections caused by community-acquired, methicillin-resistant Staphylococcus aureus were seen at Henry Ford Hospital in Detroit, Michigan. The proportion of community-acquired staphylococcal infections resistant to methicillin rose from 3 % in March 1980 to 38% in September 1981. Drug abuse, serious underlying illness, previous antimicrobial therapy, and previous hospitalization were all associated with the development of this infection. Concurrent with the community epidemic was a nosocomial epidemic of methicillin-resistant S. aureus infection, which accounted for 30.6% of all nosocomial staphylococcal infections in January 1981. Control measures that included isolation, discharge precautions for carriers, and eradication of employee carriage were effective in preventing nosocomial transmission. The prevalence of methicillin-resistant S. aureus carriage among employees was 0.7%. Methicillin-resistant S. aureus may originate in the community as well as in the hospital, and presents a threat to patients in both settings.

The clinical development of FtsZ-targeting benzamide compounds like PC190723 has been limited by poor drug-like and pharmacokinetic properties. Development of prodrugs of PC190723 (e.g., TXY541) resulted in enhanced pharmaceutical properties, which, in turn, led to improved intravenous efficacy as well as the first demonstration of oral efficacy in vivo against both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA). Despite being efficacious in vivo, TXY541 still suffered from suboptimal pharmacokinetics and the requirement of high efficacious doses. We describe here the design of a new prodrug (TXA709) in which the Cl group on the pyridyl ring has been replaced with a CF 3 functionality that is resistant to metabolic attack. As a result of this enhanced metabolic stability, the product of the TXA709 prodrug (TXA707) is associated with improved pharmacokinetic properties (a 6.5-fold-longer half-life and a 3-fold-greater oral bioavailability) and superior in vivo antistaphylococcal efficacy relative to PC190723. We validate FtsZ as the antibacterial target of TXA707 and demonstrate that the compound retains potent bactericidal activity against S. aureus strains resistant to the current standard-ofcare drugs vancomycin, daptomycin, and linezolid. These collective properties, coupled with minimal observed toxicity to mammalian cells, establish the prodrug TXA709 as an antistaphylococcal agent worthy of clinical development. Bacterial resistance has emerged as a global problem. The Centers for Disease Control and Prevention (CDC) have identified methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) as being two major antibiotic resistance threats (1). Typically, MRSA strains are resistant not only to the penicillins but also to other classes of antibiotics, including the tetracyclines, the macrolides, the aminoglycosides, and clindamycin (2-4). Current standard-of-care (SOC) drugs for the treatment of MRSA infections are therefore limited to a few drugs, which include vancomycin, daptomycin, and linezolid (3). However, resistance to these SOC drugs is already on the rise, and the clinical utility of these drugs is likely to diminish in the future (3, 5-9).The bacterial protein FtsZ has been identified as an appealing new target for the development of antibiotics that can be used to treat infections caused by multidrug-resistant (MDR) bacterial pathogens (10-14). The appeal of FtsZ as an antibiotic target lies in the essential role that the protein plays in bacterial cell division (cytokinesis). Furthermore, FtsZ is prokaryote specific with no known eukaryotic homolog. FtsZ self-polymerizes in a GTP-dependent manner to form a ring-like structure (the Z-ring) at midcell that serves as a scaffold for the recruitment and organization of other critical components for proteoglycan synthesis, septum formation, and cell division (15)(16)(17)(18)(19)(20).The substituted benzamide derivative PC190723 has been shown to inhibit bacterial cell div...

Ceftaroline (PPI 0903, formerly TAK-599), the active metabolite of a N-phosphono prodrug, ceftaroline fosamil, has been approved by the US Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. This antimicrobial agent binds to penicillin binding proteins (PBP) inhibiting cell wall synthesis and has a high affinity for PBP2a, which is associated with methicillin resistance. Ceftaroline is consistently active against multidrug-resistant Streptococcus pneumoniae and Staphylococcus aureus, including methicillin-resistant, vancomycin-intermediate, linezolid-resistant, and daptomycin-nonsusceptible strains. It possesses variable activity against Enterobacteriaceae and good activity against oral anaerobes. The drug is usually administrated intravenously at 600 mg every 12 h. Ceftaroline has low protein binding and is excreted by the kidneys and thus requires dose adjustments in individuals with renal failure. Clinical trials have demonstrated noninferiority when compared with vancomycin in the treatment of acute bacterial skin and skin structure infections and noninferiority when compared with ceftriaxone in the treatment of community-acquired bacterial pneumonia. Ceftaroline demonstrated a safety profile similar to that of comparator drugs in clinical trials.

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