Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo model

Amoxicillin-sulbactam (AMX-SUL) is an aminopenicillin/ß-lactamase inhibitor combination currently available in 29 countries and may be a suitable option for treating infections caused by Acinetobacter spp. Thus, we sought to search the optimal dosing strategy for this formulation through an ex vivo pharmacodynamic human model against Acinetobacter baumanniii. Four volunteers were randomized to receive alternatively a single dose AMX-SUL infused both either over 30 min or 3h at the following ratios (g/g): 1/0.5; 1/1, and 0/2. Time-kill studies were performed with the 0-, 0.5-, 2-, 4-, 6- and 8-h sera after dose against a clinical isolate of A. baumannii (sulbactam MIC, 4µg/mL). Bactericidal activity (i.e. a mean decrease >3 log10 CFU/mL in the viable cell counts from the initial inoculum) was displayed by the 0.5- and the 2-h sera after dose for all formulations. The 4-h sera proved inhibitory with the AMX-SUL 1g/1g formulation, albeit a trend to regrowth was observed after 24-h incubation. With the AMX-SUL 0g/2g dose, the 4-h sera proved almost bactericidal activity (i.e. a mean decrease of 2.4 log10 CFU/mL in the viable cell counts from the initial inoculum), whereas the 6-h sera was inhibitory, with a trend to regrowth after 24-h incubation. When infused over 3h, AMX-SUL 1g/0.5g and 1g/1g, bactericidal activity was displayed by the 0.5-, 2- and the 4-h sera after dose and the 6-h sera proved inhibitory with the AMX-SUL 1g/1g formulation. The present study, albeit preliminary, might give a rationale for the dosing strategy to treat infections caused by A. baumannii with sulbactam, either alone or combined with amoxicillin. A 2-g sulbactam dose seems to be optimal to be infused over 30 min with a 6-h dosing interval. When infused over 3h, AMX-SUL 1g/1g given every 6h or 8h seems a suitable dosing schedule.

Betalactámicos con inhibidores de betalactamasas: Amoxicilina-sulbactam / Betalactam antibiotics combined with bectalactamases inhibitors: Amoxicillin-sulbactam

La producción de betalactamasas constituye uno de los principales mecanismos de resistencia bacteriana a los antibióticos betalactámicos. La utilización de inhibidores de betalactamasas en combinación con antibióticos betalactámicos permite la inactivación de determinadas betalactamasas producidas por gérmenes Gram positivos, Gram negativos, anaerobios, y aun por micobacterias. Los inhibidores de betalactamasas representan una alternativa terapéutica mejorada respecto del resto de los betalactámicos al asegurar, en la mayoría de los casos, un mayor espectro antimicrobiano comparado con el de sus análogos. La actividad enzimática de las betalactamasas está dirigida específicamente a la hidrólisis del anillo betalactámico, con producción de un compuesto sin actividad antibacteriana. De acuerdo con su posición genómica dentro de los microorganismos, las betalactamasas pueden ser cromosómicas o plasmídicas. Actualmente existen tres inhibidores de betalactamasas localmente disponibles: ácido clavulánico, sulbactam y tazobactam. De ellos, sólo el sulbactam posee actividad antimicrobiana intrínseca sobre las proteínas ligadoras de penicilina. La experiencia clínica acumulada durante más de 20 años confirma que las combinaciones de betalactámicos-inhibidores de betalactamasas son efectivas en el tratamiento empírico inicial de infecciones respiratorias, intraabdominales, urinarias y ginecológicas, incluidas las de origen polimicrobiano. En el caso particular de amoxicilina-sulbactam, la evidencia citada indica que esta combinación es efectiva para el tratamiento de absceso periamigdalino, otitis media, sinusitis, neumonía extrahospitalaria, exacerbación aguda de enfermedad pulmonar obstructiva crónica (EPOC), infección del tracto urinario e infecciones ginecoobstétricas. Por su espectro y propiedades farmacológicas, la combinación amoxicilina-sulbactam constituye una excelente opción también para el tratamiento de infecciones de piel y partes blandas e infecciones intraabdominales.

Betalactamases production is one of the main bacterial resistance mechanisms to betalactam antibiotics. The use of bectalactamases inhibitors combined with betalactam antibiotics allows the inactivation of certain betalactamases produced by Gram positive, Gram negative and anaerobic organisms, and even by mycobacteria. Betalactamases inhibitors are an improved therapeutic alternative compared with the other betalactam since, in most cases, they cover a wider antimicrobial spectrum than their analogues. Betalactamases enzimatic activity is specifically directed to the betalactam ring hydrolisis, producing a compound without antibacterial activity. According to their genomic position within microorganisms, betalactamases can be either chromosomic or plasmidic. Currently there are three betalactamases inhibitors locally available: clavulanic acid, sulbactam and tazobactam. Of them, only sulbactam has an intrinsic antimicrobial activity against penicillin binding proteins. The clinical experience from over 20 years confirms that the combination of betalactam antibiotics is effective in the empirical initial treatment of respiratory, intraabdominal, urinary tract and gynecologic infections, including those of polymicrobial origin. In the specific case of amoxicillin-sulbactam, experiences have shown the effectiveness of the combination in the treatment of peritonsillar abscess, otitis media, sinusitis, community acquired pneumonia, acute exacerbation of chronic obstructive pulmonar disease (COPD), urinary tract infection and obstetric/ gynecologic infections. The spectrum and pharmacologic properties of this combination makes it also an excellent option for the treatment of skin/soft tissue and intraabdominal infections.

Efficacy and Safety of Amoxicillin-sulbactam and Ampicillin-sulbactam in Full Term Neonates

PURPOSE: Since neonatal sepsis dose not have typical symptoms and signs, whenever suspected antibiotic therapy is the mainstay of treatment. Ampicillin-sulbactam has been widely used in the newborn nursery as the empirical antibiotics as well as ampicillin and gentamicin. The purpose of this study was to compare the efficacy and safety of amoxicillin-sulbactam to ampicillin-sulbactam in treating neonatal sepsis. METHODS: A randomized, controlled study was conducted in 60 full term neonates who were suspected to have sepsis. The patients were randomly assigned to receive amoxicillin-sulbactam 30 mg/kg/day (based on amoxicillin component) intravenously divided every 12 hours or ampicillin-sulbactam 75 mg/kg/day (based on ampicillin component) intravenously divided every 8 hours for at least 7 consecutive days. Clinical symptoms and signs, complete blood cell counts, blood chemistry and body fluid cultures were taken before, during and after the treatment. All patients were evaluated for clinical efficacy on the basis of the clinical, microbiological responses and side effects. RESULTS: The clinical success rates after 7 days of treatment were 100% for both groups. Drug related serious side effects did not occur in all patients. There were three cases (10%) of bacterial culture positive patients in amoxicillin-sulbactam treated group during treatment. But no more bacterial growth had found after 7 days antibiotics treatment. CONCLUSION: Amoxicillin-sulbactam was as effective and safe as ampicillin-sulbactam for whom neonatal sepsis was suspected.

Determination of Sulbactam Pivoxil and the Related Substances in Amoxicillin Sulbactam Pivoxil Dispersible Tablets by HPLC-DAD / 中国药房

OBJECTIVE: To establish an HPLC-DAD method for the determination of sulbactam pivoxil and the related substnaces in amoxicillin sulbactam pivoxil dispersible tablets. METHODS: The chromatographic column was Hypersil BDS with mobile phase consisted of potassium dihydrogen phosphate solution∶acetonitrile (40∶60) at a flow rate of 1.0 mL?min-1. The detector was diode array detector (DAD) at a detection wavelength of 204 nm and spectrum range of 300～190 nm. The injection volume was 10 ?L. RESULTS: The linear range of sulbactam pivoxil was 119.83～119 8.3 ?g? mL-1(r=0.999 9),with an average recovery rate of 98.7%(RSD=0.65%). The content of the related substances was 1.02%～1.10%. CONCLUSION: The method is simple and accurate,and it can be used for the quality control of amoxicillin sulbactam pivoxil dispersible tablets.

Bacteriological Efficacy of Amoxicillin/sulbactam on Acute Bacterial Infections / 中华医院感染学杂志

0.05);the bacterial sensitive rates of amoxicillin/(sulbactam),(amoxicillin)/clavulanate,amoxicillin,ampicillin/sulbactam and cefotaxime were 88.42%,86.78%,57.02%,(86.78%) and 85.95%,respectively;the antibacterial potency of amoxicillin/sulbactam was higher than(amoxicillin)/clavulanate that of from the results of MIC_(90).CONCLUSIONS Amoxicillin/sulbactam has good (bacteriological) efficacy.