minocycline and sultamicillin

Complicated skin and skin structure infections (cSSSIs) frequently result in hospitalization with significant morbidity and mortality.. In this phase 3b/4 parallel, randomized, open-label, comparative study, 531 subjects with cSSSI received tigecycline (100 mg initial dose, then 50 mg intravenously every 12 hrs) or ampicillin-sulbactam 1.5-3 g IV every 6 hrs or amoxicillin-clavulanate 1.2 g IV every 6-8 hrs. Vancomycin could be added at the discretion of the investigator to the comparator arm if methicillin-resistant Staphylococcus aureus (MRSA) was confirmed or suspected within 72 hrs of enrollment. The primary endpoint was clinical response in the clinically evaluable (CE) population at the test-of-cure (TOC) visit. Microbiologic response and safety were also assessed. The modified intent-to-treat (mITT) population comprised 531 subjects (tigecycline, n = 268; comparator, n = 263) and 405 were clinically evaluable (tigecycline, n = 209; comparator, n = 196).. In the CE population, 162/209 (77.5%) tigecycline-treated subjects and 152/196 (77.6%) comparator-treated subjects were clinically cured (difference 0.0; 95% confidence interval [CI]: -8.7, 8.6). The eradication rates at the subject level for the microbiologically evaluable (ME) population were 79.2% in the tigecycline treatment group and 76.8% in the comparator treatment group (difference 2.4; 95% CI: -9.6, 14.4) at the TOC assessment. Nausea, vomiting, and diarrhea rates were higher in the tigecycline group.. Tigecycline was generally safe and effective in the treatment of cSSSIs.. ClinicalTrials.gov NCT00368537.

Topics: Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; Female; Humans; Male; Middle Aged; Minocycline; Skin Diseases, Bacterial; Skin Diseases, Infectious; Sulbactam; Tigecycline

Multidrug resistance is common among Acinetobacter baumannii, limiting the available options used to treat infections caused by this organism. The objective of this study was to compare monotherapy and combination therapy with ampicillin/sulbactam, doripenem and tigecycline against multidrug-resistant A. baumannii using an in vitro pharmacodynamic model.. Human free-drug concentration profiles of clinically relevant ampicillin/sulbactam, doripenem and tigecycline were simulated alone and in two-drug combinations against four clinical A. baumannii isolates (MICs: ampicillin/sulbactam, 4/2-64/32 mg/L; doripenem, 16 to ≥64 mg/L; and tigecycline, 1-4 mg/L) over 24 h. Microbiological response was measured as log10 cfu/mL and the area under the bactericidal curve (AUBC).. Control strains grew to 7.11 ± 0.13 log10 cfu/mL. Except for ampicillin/sulbactam-containing regimens against the single ampicillin/sulbactam-susceptible isolate, all A. baumannii demonstrated regrowth to 24 h control levels against all mono and combination regimens. Using AUBC as an endpoint, the most active regimens were 9 g of ampicillin/sulbactam every 8 h (3 h infusion) + 2 g of doripenem every 8 h (4 h infusion; 87.8 ± 21.0), 9 g of ampicillin/sulbactam every 8 h (3 h infusion) + 200 mg of tigecycline every 12 h (30 min infusion; 100.6 ± 33.0) and 9 g of ampicillin/sulbactam every 8 h (3 h infusion) monotherapy (116.7 ± 31.6), followed by 3 g of ampicillin/sulbactam every 6 h (30 min infusion) + 200 mg of tigecycline every 12 h (30 min infusion; 134.0 ± 31.5) and 2 g of doripenem every 8 h (4 h infusion) + 200 mg of tigecycline every 12 h (30 min infusion; 142.7 ± 16.9).. Although specific combination regimens displayed additive activity at aggressive doses against these multidrug-resistant A. baumannii, none of the regimens could maintain cfu reductions against the more resistant isolates.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; Bacterial Load; Carbapenems; Doripenem; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; In Vitro Techniques; Minocycline; Models, Theoretical; Sulbactam; Tigecycline

Multidrug-resistant Acinetobacter baumannii infections are serious challenges for clinicians because of A. baumannii propensity to acquire resistance to a wide spectrum of antimicrobial agents. In this study, 91 A. baumannii isolates from patients in tertiary intensive care units of three university hospitals in the north, central, and south of Iran were selected and tested for susceptibility to 22 antimicrobials; amplified restriction fragment polymorphism and multiplex polymerase chain reaction methods were used to determine genetic relationships and International Clone (IC) of A. baumannii isolates, respectively. Twenty-four genotypes were identified in A. baumannii isolates. About 91.2% of isolates categorized into 4 distinct clusters; one was more heterogeneous and observed across the three locations. A considerable number of the isolates (27.5%) belonged to the novel IC variant, sequence group 7 (SG7), which was geographically widespread in three locations. The drug resistance pattern showed that 14.2%, 20%, and 77% of the A. baumannii isolates were resistant to colistin, tigecycline, and rifampicin, respectively. Nine percent of isolates (8) showed simultaneous resistance to colistin, rifampicin, and tigecycline. Interestingly, all of them were susceptible to ampicillin-sulbactam and/or tobramycin. According to our results, SG7 could be considered as a pan-Iranian clone.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; Bacterial Typing Techniques; Clone Cells; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Iran; Microbial Sensitivity Tests; Minocycline; Multiplex Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Prevalence; Rifampin; Sulbactam; Tertiary Healthcare; Tigecycline; Tobramycin

Although polymicrobial infections, such as peri-implantitis or periodontitis, were postulated in the literature to be caused by synergistic effects of bacteria, these effects remain unclear looking at antibiotic susceptibility. The aim of this study is to compare the antibiotic susceptibilities of pure cultures and definite cocultures.. Laboratory strains of Aggregatibacter actinomycetemcomitans (Aa) (previously Actinobacillus actinomycetemcomitans), Capnocytophaga ochracea (Co), and Parvimonas micra (Pm) (previously Peptostreptococcus micros) were cultivated under anaerobic conditions, and their susceptibilities to 10 antibiotics (benzylpenicillin G, ampicillin, amoxicillin, ampicillin/sulbactam, amoxicillin/clavulanic acid, minocycline, metronidazole, linezolid, azithromycin, and moxifloxacin) were tested using the Epsilometertest. Cocultures, each consisting of two or three bacteria, were treated analogously.. All four cocultures showed lower susceptibilities to azithromycin and minocycline than to pure cultures. The coculture Aa-Co showed a lower susceptibility to moxifloxacin as did the coculture Aa-Pm to benzylpenicillin G; the coculture Co-Pm showed a lower susceptibility to amoxicillin, amoxicillin/clavulanic acid, metronidazole, and benzylpenicillin G. However, the coculture Co-Pm showed a higher susceptibility to ampicillin, linezolid and moxifloxacin as did Aa-Pm and Aa-Co-Pm to linezolid.. In addition to established in vitro assays, it was demonstrated that antimicrobial cocultures caused antibiotic susceptibilities that differed from those of pure cultures. Bacterial cocultures frequently showed lowered susceptibilities to antibiotics.

Topics: Acetamides; Actinobacillus Infections; Aggregatibacter actinomycetemcomitans; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Azithromycin; Capnocytophaga; Coculture Techniques; Coinfection; Drug Resistance, Bacterial; Fluoroquinolones; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Linezolid; Metronidazole; Microbial Interactions; Minocycline; Moxifloxacin; Oxazolidinones; Penicillin G; Peptostreptococcus; Peri-Implantitis; Periodontitis; Quinolines; Sulbactam