amoxicillin-potassium-clavulanate-combination and Anthrax

Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies.. We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans.. We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, β-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx.. These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anthrax; Anti-Bacterial Agents; Anti-Infective Agents; Bacillus anthracis; beta-Lactams; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Doxycycline; Glycopeptides; Humans; Levofloxacin; Lipopeptides; Models, Animal; Tetracyclines; United States

As Bacillus anthracis spores pose a proven bio-terror risk, the treatment focus has shifted from exposed populations to anthrax patients and the need for effective antibiotic treatment protocols increases. The CDC recommends carbapenems and Linezolid (oxazolidinone), for the treatment of anthrax, particularly for the late, meningeal stages of the disease. Previously we demonstrated that treatment with Meropenem or Linezolid, either as a single treatment or in combination with Ciprofloxacin, fails to protect rabbits from anthrax-meningitis. In addition, we showed that the failure of Meropenem was due to slow BBB penetration rather than low antibacterial activity. Herein, we tested the effect of increasing the dose of the antibiotic on treatment efficacy. We found that for full protection (88% cure rate) the dose should be increased four-fold from 40 mg/kg to 150 mg/kg. In addition, B. anthracis is a genetically stable bacterium and naturally occurring multidrug resistant B. anthracis strains have not been reported. In this manuscript, we report the efficacy of classical β-lactams as a single treatment or in combination with β-lactamase inhibitors in treating anthrax meningitis. We demonstrate that Ampicillin based treatment of anthrax meningitis is largely efficient (66%). The high efficacy (88-100%) of Augmentin (Amoxicillin and Clavulonic acid) and Unasyn (Ampicillin and Sulbactam) makes them a favorable choice due to reports of β-lactam resistant B. anthracis strains. Tazocin (Piperacillin and Tazobactam) proved inefficient compared to the highly efficient Augmentin and Unasyn.

Topics: Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Animals; Anthrax; Anti-Bacterial Agents; Bacillus anthracis; Bacteria; beta-Lactamase Inhibitors; beta-Lactams; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Meropenem; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Rabbits; Sulbactam

Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with Bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10(5) CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anthrax; Anti-Bacterial Agents; Bacillus anthracis; Bacteremia; Ciprofloxacin; Clarithromycin; Disease Models, Animal; Doxycycline; Drug Combinations; Drug Synergism; Humans; Imipenem; Linezolid; Male; Microbial Sensitivity Tests; Rabbits; Respiratory Tract Infections; Rifampin; Spores, Bacterial; Survival Analysis; Vancomycin

Anthrax is an infectious disease that is not well known by ophthalmologists. In its cutaneous form, it may produce lesions of the eyelids. We report eight cases of palpebral anthrax. All patients presented with a black necrotic eschar and a tegumentary edema, with a history of contact with sick animals. The curative treatment was based on intravenous penicillin G in four cases and amoxicillin-clavulanic acid in the four other cases. The palpebral lesions resolved, leaving no clinical evidence of eyelid abnormalities in six patients. Only two patients developed a cicatricial ectropion and a palpebral symphysis. Although palpebral anthrax is a rare disease in humans, ophthalmologists should be aware of its symptoms and management.

Topics: Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anthrax; Blepharitis; Child; Conjunctivitis, Bacterial; Ectropion; Female; Humans; Male; Middle Aged; Penicillin G