piperacillin--tazobactam-drug-combination and sultamicillin

Broad-spectrum beta-lactam antibiotics have several advantages in the treatment of intra-abdominal infections. These agents are effective against gram-negative rods and anaerobes, reach therapeutic levels rapidly after parenteral administration, and, in the absence of penicillin allergy, generally exhibit low toxicity. The second-generation cephalosporins (e.g., cefoxitin, cefotetan) are used widely in surgical prophylaxis, trauma, and treatment of mild-to-moderate community-acquired infections, but limitations in their spectra and microbial resistance restrict their utility in more serious infections. Extended-spectrum penicillin/beta-lactamase-inhibitor combinations are effective in the treatment of intra-abdominal infections and include enterococci in their spectrum. Gram-negative aerobe resistance has developed to ampicillin/sulbactam. Piperacillin/tazobactam, a ureidopenicillin with increased gram-negative coverage and enhanced antipseudomonal activity, has proved to be effective in clinical trial therapy for intra-abdominal infections. The very broad spectrum carbapenems--imipenem/cilastatin and meropenem--are effective for serious infections or resistant organisms and are often used in the intensive care unit or for nosocomial intra-abdominal infection. These classes of beta-lactams comprise a range of antimicrobials that can be targeted effectively as single agents to both prevention and treatment of intra-abdominal infection.

Topics: Abdomen; Abdominal Abscess; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamase Inhibitors; Carbapenems; Cephalosporins; Clavulanic Acids; Drug Resistance, Bacterial; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Surgical Wound Infection; Ticarcillin

Soft tissue and bone infections of the lower limb continue to be a frequent and serious complication in patients with diabetes mellitus. The best choice of antimicrobial for the empiric treatment of moderate to severe diabetic foot infections has not been established clearly.. We conducted a prospective, randomized, open-label, multicenter trial comparing piperacillin/tazobactam (P/T) (4 g/0.5 g q8h) and ampicillin/sulbactam (A/S) (2 g/1 g q6h) as a parenteral treatment for 314 adult patients with moderate-to-severe infected diabetic foot ulcers. Patients with polymicrobial infections involving methicillin-resistant Staphylococcus aureus also received vancomycin 1 g q12h.. Clinical efficacy rates (cure or improvement) were statistically equivalent overall (81% for P/T vs. 83.1% for A/S), and median duration of treatment was similar in the clinically evaluable populations (nine days for P/T, 10 days for A/S). Drug-related adverse events for both study drugs were comparable in frequency and type.. Although both study drugs provide safe and effective empiric treatment for moderate-to-severe infected diabetic foot ulcers, piperacillin/tazobactam has the advantage of covering Pseudomonas aeruginosa (bacteriologic success rate of 85.7%), the most commonly isolated gram-negative pathogen in this study.

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Diabetic Foot; Female; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sulbactam; Time Factors; Vancomycin; Wound Infection

This study aimed to compare treatment outcomes for bloodstream infections (BSI) caused by a piperacillin/tazobactam (PIP/TAZ)-susceptible E. coli among three patient groups: BSI caused by ampicillin/sulbactam (AMP/SLB)-resistant isolates treated with PIP/TAZ, BSI caused by AMP/SLB-sensitive isolates treated with PIP/TAZ, and BSI caused by AMP/SLB-resistant isolates treated with another monotherapy.. This retrospective study was conducted in two academic centres in Europe. Adult patients with E. coli BSI were screened from 2014 to 2020. Inclusion criteria were non-ESBL BSI and initial monotherapy for ≥ 72 h. To reduce the expected bias between the patient groups, propensity score matching was performed. The primary outcome was early treatment response after 72 h and required absence of SOFA score increase in ICU/IMC patients, as well as resolution of fever, leukocytosis, and bacteraemia.. Of the 1707 patients screened, 315 (18.5%) were included in the final analysis. Urinary tract infection was the most common source of BSI (54.9%). Monotherapies other than PIP/TAZ were cephalosporins (48.6%), carbapenems (34.3%), and quinolones (17.1%). Enhanced early treatment response rate was detected (p = 0.04) in patients with BSI caused by AMP/SLB-resistant isolates treated with another monotherapy (74.3%) compared to those treated with PIP/TAZ (57.1%), and was mainly driven by the use of cephalosporins and quinolones (p ≤ 0.03). Clinical success, 28-day mortality, and rate of relapsing BSI did not significantly differ between the groups.. Our study suggests that initial use of PIP/TAZ may be associated with reduced early treatment response in E. coli BSI caused by AMP/SLB-resistant isolates compared to alternative monotherapies.

Topics: Adult; Ampicillin; Anti-Bacterial Agents; Bacteremia; Cephalosporins; Cohort Studies; Escherichia coli; Escherichia coli Infections; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Quinolones; Retrospective Studies; Sulbactam

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Antifungal Agents; Antimicrobial Stewardship; Aspergillosis; Azithromycin; Bacterial Infections; Cohort Studies; Coinfection; COVID-19; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Germany; Humans; Klebsiella Infections; Linezolid; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Practice Patterns, Physicians'; Retrospective Studies; SARS-CoV-2; Staphylococcal Infections; Streptococcal Infections; Sulbactam; Vancomycin; Young Adult

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

The in vitro susceptibilities of Bacteroides fragilis to antimicrobial agents, especially to carbapenem, are a major concern in the treatment of patients with bloodstream infections. In this study, 50 isolates of B. fragilis were obtained from positive blood bottles from 2014 to 2019 in Saitama, Japan. Their susceptibility to ampicillin/sulbactam was reduced to 70.0% compared with a previous report, whereas they were still sufficiently susceptible to piperacillin/tazobactam (94.0%). Five cfiA-positive isolates (5/50, 10.0%) were identified that were resistant to doripenem and meropenem, and two of them carried an insertion sequence located upstream of the cfiA-coding region. In particular, imipenem should be considered as a first-line carbapenem for the empirical treatment of B. fragilis infection because only insertion sequence and cfiA double-positive strains showed resistance to imipenem. Thirty-six percent of the isolates had a reduced minimum inhibitory concentration for moxifloxacin. In addition, metronidazole should still be considered as an active agent for B. fragilis because all isolates were susceptible to this antibiotic and the prevalence of the nim gene was low in Japan.

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Proteins; Bacteroides fragilis; Bacteroides Infections; beta-Lactamases; Blood Culture; DNA Transposable Elements; Doripenem; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Humans; Imipenem; Japan; Meropenem; Metronidazole; Microbial Sensitivity Tests; Moxifloxacin; Piperacillin, Tazobactam Drug Combination; Prevalence; Sulbactam; Tertiary Care Centers

The prevalence and antibiotic resistance of Acinetobacter spp. from fifty samples of meat (chicken, turkey, beef and pork) were evaluated. Acinetobacter spp. was recovered from all samples and the clonal relatedness of 223 isolates identified to belong to the genus Acinetobacter was established by PFGE. A high genetic diversity was observed and 166 isolates from different samples, 141 representing different PFGE profiles, were further identified to the species level by rpoB gene sequencing. Thirteen distinct Acinetobacter species were identified among 156 isolates. The remaining ten isolates may represent three putatively novel species since rpoB sequence homologies with type strains of all available described Acinetobacter species, were <95%. The most common species was Acinetobacter guillouiae with a prevalence of 34.9%. However 18.7% of the strains belong to the Acinetobacter baumannii group (n=31) which include the species Acinetobacter baumannii (n=7), Acinetobacter pittii (n=12), Acinetobacter seifertii (n=8) and Acinetobacter nosocomialis (n=4) that are the species most frequently associated with nosocomial infections worldwide. In general, strains were resistant to some of the antimicrobials most frequently used to treat Acinetobacter infections such as piperacillin-tazobactam (64.9% of strains resistant), ceftazidime (43.5%), ciprofloxacin (42.9%), as well as to colistin (41.7%) and polymyxin B (35.1%), the last-resort drugs to treat infections caused by multidrug-resistant Acinetobacter. The percentage of resistant strains to trimethoprim-sulfamethoxazole, tetracycline, aminoglycosides (amikacin and tobramycin) and ampicillin-sulbactam was >10% (23.2%, 23.2%, 14.3%, 12.5%, 12.5%, respectively). However, resistances to meropenem, imipenem and minocycline were only sporadically observed (8.3%, 1.2% and 1.2%, respectively). Overall, 51.2% of the strains were considered as multidrug-resistant (MDR) and 9.6% as extensively drug-resistant (XDR). The prevalence of MDR strains within the A. baumannii group (38.7%) was lower than the prevalence within the others species identified (54.1%). Therefore, food of animal origin may be a vehicle of spread Acinetobacter strains resistant to several antibiotics in the community and in the hospital setting environment. This may led to nosocomial and community-acquired infections in susceptible individuals.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Animals; Anti-Bacterial Agents; Cattle; Ceftazidime; Chickens; Ciprofloxacin; Cross Infection; DNA-Directed RNA Polymerases; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prevalence; Red Meat; Sulbactam; Swine; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the antimicrobial susceptibility of Gram-negative bacilli that caused hospital-acquired and community-acquired intra-abdominal infections (IAIs) in China between 2012 and 2013, we determined the susceptibilities to 12 antimicrobials and the extended-spectrum β-lactamase (ESBL) statuses of 3,540 IAI isolates from seven geographic areas in China in a central laboratory using CLSI broth microdilution and interpretive standards. Most infections were caused by Escherichia coli (46.3%) and Klebsiella pneumoniae (19.7%). Rates of ESBL-producing E. coli (P = 0.031), K. pneumoniae (P = 0.017), and Proteus mirabilis (P = 0.004) were higher in hospital-acquired IAIs than in community-acquired IAIs. Susceptibilities of enterobacteriaceae to ertapenem, amikacin, piperacillin-tazobactam, and imipenem were 71.3% to 100%, 81.3% to 100%, 64.7% to 100%, and 83.1% to 100%, respectively, but imipenem was ineffective against P. mirabilis (<20%). Although most ESBL-positive hospital-acquired isolates were resistant to third- and fourth-generation cephalosporins, the majority were susceptible to cefoxitin (47.9% to 83.9%). Susceptibilities of ESBL-positive isolates to ampicillin-sulbactam (<10%) were low, whereas susceptibilities to ciprofloxacin (0% to 54.6%) and levofloxacin (0% to 63.6%) varied substantially. The prevalences of cephalosporin-susceptible E. coli and K. pneumoniae were higher in the northeastern and southern regions than in the central and eastern regions, reflecting the ESBL-positive rates in these areas, and were lowest in the Jiangsu-Zhejiang (Jiang-Zhe) area where the rates of carbapenem resistance were also highest. Ertapenem, amikacin, piperacillin-tazobactam, and imipenem are the most efficacious antibiotics for treating IAIs in China, especially those caused by E. coli or K. pneumoniae. Resistance to cephalosporins and carbapenems is more common in the Jiang-Zhe area than in other regions in China.

Topics: Amikacin; Ampicillin; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Cefoxitin; China; Ciprofloxacin; Community-Acquired Infections; Cross Infection; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Ertapenem; Gene Expression; Humans; Imipenem; Intraabdominal Infections; Levofloxacin; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam

In liver transplant (LT) recipients, surgical site infection (SSI) represents an important cause of morbidity and mortality.. This study measures the impact of a multimodal approach to the incidence of surgical site infection in LT recipients.. All of the LT recipients in our department were registered on the national database in solid organ transplant. A study was performed in two analytical-interventional phases. Phase 1 took place between July 14, 2009, and February 20, 2014. Phase 2 took place between February 21, 2014, and July 15, 2015. The multimodal change implemented during phase 1 was that 0.5% alcoholic chlorhexidine and ether were applied to the surgical field; surgical prophylaxis was primarily with ampicillin/sulbactam plus cefazolin. In phase 2, 2% alcoholic chlorhexidine alone was applied to the surgical field. The prior standard prophylaxis was changed to piperacillin tazobactam administered during surgery as a continuous infusion of 13.5 g over 8 hours with a pre-incision loading dose of 4.5 g. The loading dose of piperacillin tazobactam was combined with a single dose of gentamicin of 5 mg/kg.. One hundred eight patients have received transplants since the start of the program: 82 patients during phase one and 26 patients during phase two. During phase 1, 13 cases of SSI were recorded, representing a rate of 15.85 per 100 transplants. Sixteen micro-organisms were isolated during phase 1, of which 12 corresponded to gram-negative bacilli. With regard to resistance profiles, 13 showed multidrug resistant and extensively drug resistant profiles. During phase 2, no cases of SSI were recorded (relative risk = 0.158 [95% confidence interval 0.0873-0.255], P = .0352].. A multimodal approach allowed for the reduction of the incidence of SSI in LTs and offered a protective strategy.

Topics: Administration, Cutaneous; Adult; Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents, Local; Antibiotic Prophylaxis; Cefazolin; Chlorhexidine; Drug Administration Schedule; Drug Therapy, Combination; Ether; Female; Gentamicins; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Infusions, Intravenous; Liver Transplantation; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Surgical Wound Infection; Transplant Recipients

Negligible in vivo growth of enterococci and high-level dispersion of data have led to inaccurate estimations of antibiotic pharmacodynamics (PD). Here we improved an in vivo model apt for PD studies by optimizing the in vitro culture conditions for enterococci. The PD of vancomycin (VAN), ampicillin-sulbactam (SAM), and piperacillin-tazobactam (TZP) against enterococci were determined in vivo, comparing the following different conditions of inoculum preparation: aerobiosis, aerobiosis plus mucin, and anaerobiosis plus mucin. Drug exposure was expressed as the ratio of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (fAUC/MIC) (VAN) or the time in a 24-h period that the drug concentration for the free, unbound fraction exceeded the MIC under steady-state pharmacokinetic conditions (fT(>MIC)) (SAM and TZP) and linked to the change in log10 CFU/thigh. Only anaerobiosis plus mucin enhanced the in vivo growth, yielding significant PD parameters with all antibiotics. In conclusion, robust in vivo growth of enterococci was crucial for better determining the PD of tested antibacterial agents, and this was achieved by optimizing the procedure for preparing the inoculum.

Topics: Ampicillin; Anaerobiosis; Animals; Anti-Bacterial Agents; Disease Models, Animal; Enterococcus faecalis; Female; Gram-Positive Bacterial Infections; Mice, Inbred ICR; Microbial Sensitivity Tests; Mucins; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Vancomycin

To investigate the mechanism of drug resistance of carbapenems-resistant Acinetobacter baumannii (CRAB) in burn patients and the antimicrobial activity of a combination of drugs against this bacteria in vitro.. A total of 135 strains of Acinetobacter baumannii (AB) from wound excretion, sputum, and venous catheter wall of patients hospitalized in our department from January 2011 to July 2013 were collected individually. Drug resistance of 135 strains of AB to 12 antibiotics commonly-used in clinic was detected using K-B paper diffusion method. Among the CRAB strains, double-disk synergy test was used to screen metallo-β-lactamase (MBL)-producing strains, and the drug resistance rates between MBL-producing strains and non-MBL-producing strains were compared. Minimal inhibitory concentration (MIC), 50% MIC (MIC50), and 90% MIC (MIC90) of cefoperazone/sulbactam, imipenem, cefepime, ampicillin/sulbactam, and amikacin used alone against MBL-producing CRAB were determined by broth microdilution method. MIC, MIC50, and MIC90 of amikacin respectively combined with imipenem, cefoperazone/sulbactam, cefepime, or ampicillin/sulbactam against MBL-producing CRAB were determined by checkerboard method with diluted agar. Fractional inhibitory concentration (FIC) index was calculated to determine the antibacterial effect of each combination of two antibiotics. Synergy with FIC lower than or equal to 0.5, or additivity with FIC higher than 0.5 and lower than or equal to 1.0 was regarded as effective, and indifference with FIC higher than 1.0 and lower than or equal to 2.0 or antagonism with FIC higher than 2.0 was regarded as ineffective. The effective rate was calculated. Data were processed with Chi-square test.. The resistant rates of the 135 strains of AB to imipenem, meropenem, and ceftazidime were high, and those of piperacillin/tazobactam and ampicillin/sulbactam were low. A total of 120 strains of CRAB was screened, accounting for 88.89%, among which the MBL-producing strains accounted for 78.33% (94/120). The resistant rates of MBL-producing strains to piperacillin/tazobactam, imipenem, meropenem, piperacillin, and cefepime were respectively 59.5%, 87.2%, 93.5%, 87.0%, 86.0%, and they were significantly higher than those of non-MBL-producing strains (respectively 43.0%, 81.3%, 87.5%, 78.4%, 64.0%, with χ(2) values from 4.571 to 8.260, P < 0.05 or P < 0.01). Among the inhibition concentrations of each of the 5 antibiotics used alone against MBL-producing strains, MIC, MIC50, and MIC90 of ampicillin/sulbactam were the lowest, respectively 4.00, 16, 64 µg/mL, while those of cefepime were high, respectively 32.00, 128, 512 µg/mL. MIC, MIC50, and MIC90 of amikacin combined with each of the other 4 antibiotics were decreased from 50.00% to 98.44% as compared with that of single administration of each antibiotic. Among the 94 strains of MBL-producing CRAB, the synergic, additive, indifferent, and antagonistic effects were respectively observed in 40, 33, 6, and 15 strains applied with combination of amikacin and ampicillin/sulbactam; 42, 30, 5, 17 strains applied with combination of amikacin and cefoperazone/sulbactam; 38, 15, 19, 22 strains applied with combination of amikacin and cefepime; 34, 2, 37, 21 strains applied with combination of amikacin and imipenem, among which the antibacterial effective rates decreased successively, respectively 77.7%, 76.6%, 56.4%, and 38.3%. The former two rates were respectively significantly higher than the latter two rates (with χ(2) values from 8.618 to 29.889, P values below 0.01).. Production of MBL is the main mechanism of resistance of the CRAB isolated from burn patients hospitalized in our department against carbapenems in about 3 years. The antibacterial effects of amikacin combined with each of the former-mentioned 4 agents are better than those of each of the five antibiotics used singly, and the effects are particularly obvious when combining amikacin with compound agent containing enzyme inhibitors.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Carbapenems; Cefepime; Cephalosporins; Drug Resistance; Humans; In Vitro Techniques; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Pharmaceutical Preparations; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Thienamycins

The FDA recently issued guidance for the types of infections that should be included in trials to support an indication for antibacterial treatment. The latest FDA guidance recommends assessing response to drug therapy at 48 to 72 hours as the primary endpoint in clinical trials. This study evaluated clinical and economic outcomes among acute bacterial skin and skin structure infections (ABSSSI) patients hospitalized at a 3000-bed healthcare system in New Jersey.. In this retrospective cohort analysis, adult ABSSSI patients hospitalized between July 2010 and December 2011 were stratified based on infection type: cellulitis/erysipelas and major cutaneous abscess, wound infection, and all ABSSSI. Initial antibiotic therapy was assessed by individual agent, regimen, and MRSA coverage. Day 3 response to initial antibiotic therapy was evaluated based on temperature and lesion cessation outcomes; clinical response rates were assessed by initial therapy and pathogen for each cohort. The impact of response on length of stay (LOS), cost of care, and antibiotic treatment duration were also evaluated.. Commonly used antibiotics included vancomycin, cefazolin, piperacillin-tazobactam, and ampicillin-sulbactam; over 40% of patients received empiric therapy with activity against MRSA. Clinical non-response to initial antimicrobial therapy at Day 3 was 39.9%, 30.3%, and 60.7%, for all ABSSSI, cellulitis/abscess, and wound infection patients, respectively. The cost of care among non-responders was over 1.5 times that of responders (p < 0.0001). Non-response to initial therapy was associated with a 3.7 day increase in duration of antibiotic treatment (p < 0.0001).. Results of this study demonstrate that a significant percentage of ABSSSI patients, particularly those with wound infection, were not achieving clinical response at Day 3 of therapy. Failure to respond to drug therapy is associated with substantial increases in LOS, antibiotic treatment duration, and cost of care.. This had the inherent limitations associated with a retrospective chart review; because data was initially collected for clinical rather than research purposes, certain information may have been absent, incomplete, or missed by data abstractors.

Topics: Aged; Ampicillin; Anti-Bacterial Agents; Cefazolin; Female; Hospitalization; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Skin Diseases, Bacterial; Skin Diseases, Infectious; Sulbactam; Treatment Outcome; Vancomycin

Several aerosol antibiotics are on the market and several others are currently being evaluated. Aim of the study was to evaluate the aerosol droplet size of five different antibiotics for future evaluation as an aerosol administration.. The nebulizers Sunmist(®), Maxineb(®) and Invacare(®) were used in combination with four different "small <6 ml" residual cups and two "large <10 ml" with different loadings 2-4-6-8 ml (8 ml only for large residual cups) with five different antibiotic drugs (ampicilln-sulbactam, meropenem, ceftazidime, cefepime and piperacillin-tazobactam). The Mastersizer 2000 (Malvern) was used to evaluate the produced droplet size from each combination. Significant effect on the droplet size produced the different antibiotic (F=96.657, p<0.001) and the residual cup design (F=68.535, p<0.001) but not the different loading amount (p=0.127) and the nebulizer (p=0.715). Interactions effects were found significant only between antibiotic and residual cup (F=16.736, p<0.001). No second order interactions were found statistically significant.. Our results firstly indicate us indirectly that the chemical formulation of the drug is the main factor affecting the produced droplet size and secondly but closely the residual cup design.

Topics: Aerosols; Ampicillin; Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Chemistry, Pharmaceutical; Equipment Design; Meropenem; Nebulizers and Vaporizers; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Thienamycins

Appendicitis is a frequent clinical condition in normal children that may be complicated by community-acquired secondary peritonitis (CASP). We evaluated the potential efficacy of different drugs for initial treatment of this condition, as recommended by recent Consensus Conference and Guidelines for paediatric patients. Susceptibility to ampicillin-sulbactam, ertapenem, gentamycin, piperacillin, piperacillin-tazobactam, vancomycin, and teicoplanin was evaluated according to EUCST 2012 recommendations in aerobic bacteria isolated from peritoneal fluid in CASP diagnosed from 2005 to 2011 at 'Istituto Giannina Gaslini', Genoa, Italy. A total of 114 strains were analysed: 83 E. coli, 15 P. aeruginosa, 6 Enterococci, and 10 other Gram-negatives. Resistance to ampicillin-sulbactam was detected in 37% of strains, while ertapenem showed a potential resistance of 13% (all P. aeruginosa strains). However, the combination of these drugs with gentamicin would have been increased the efficacy of the treatment to 99 and 100%, respectively. Resistance to piperacillin-tazobactam was 3%, while no strain was resistant to meropenem. Our data suggest that monotherapy with ampicillin-sulbactam or ertapenem for community-acquired secondary peritonitis would present a non-negligible rate of failure, but the addition of gentamycin to these drugs could reset to zero this risk. On the contrary, monotherapy with piperacillin-tazobactam or meropenem is highly effective.

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Child; Community-Acquired Infections; Drug Resistance, Bacterial; Drug Therapy, Combination; Ertapenem; Gentamicins; Hospitals, Pediatric; Humans; Italy; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Sulbactam; Thienamycins

Klebsiella pneumoniae is an important causative bacterium of aspiration pneumonia in many elderly patients. We retrospectively investigated the clinical effects of the early treatment of aspiration pneumonia and background factors in 24 patients from whom Klebsiella pneumoniae was isolated. Sulbactam/ampicillin (SBT/ABPC) was selected for early treatment in 12 of the 24 patients diagnosed with aspiration pneumonia, and tazobactam/piperacillin (TAZ/PIPC) was selected for the other patients. The effective rates and success rates of early treatment were significantly higher in the TAZ/PIPC group than in the SBT/ABPC group (p = 0.003 and 0.027, respectively). Although no significant difference was noted because of the limited number of cases, the survival rates after 30 days were 91.7 and 58.3 % in the TAZ/PIPC and SBT/ABPC groups, respectively. Several bacteria isolated with Klebsiella pneumoniae were resistant bacteria, such as methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa, and no anaerobe or extended-spectrum β-lactamase-producing Klebsiella pneumoniae was isolated. Thirteen and 11 of the 24 cases were classified as healthcare-associated pneumonia (HCAP) and hospital-acquired pneumonia (HAP), respectively, with no case classified as community-acquired pneumonia (CAP). As population aging progresses, the frequency of aspiration pneumonia classified as HCAP will increase. To cover anaerobes, it is necessary to select antibacterial drugs, such as TAZ/PIPC, for early treatment in consideration of resistant gram-negative bacteria to improve the outcome, and not drugs with weak activity against these bacteria.

Topics: Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Bacteria; C-Reactive Protein; Drug Therapy, Combination; Humans; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Aspiration; Retrospective Studies; Sulbactam; Treatment Outcome

Topics: Aeromonas; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Animals; Anti-Bacterial Agents; Cattle; Clavulanic Acids; Lactoferrin; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Ticarcillin

The double-disk synergy test (DDST) using Mueller-Hinton agar and antibiotic disks with centrally positioned disks of amoxicillin-clavulanate, ampicillin-sulbactam, and piperacillin-tazobactam and, at a center-to-center distance of 25-30 mm, 2-4 disks with 10 various beta-lactam antibiotics per one plate was performed in 58 clinical isolates of Stenotrophomonas maltophilia to determine the effectivity of 3 beta-lactamase inhibitors. When tested with clavulanate as the central beta-lactamase inhibitor synergic action on tested strains was the most frequent with aztreonam (81.0% of strains), cefoperazone (63.8%), and cefepime (60.3%). With sulbactam the synergic action, i.e. DDST positivity, was high in the case of cefoperazone (15.5%), ampicillin, aztreonam and piperacillin (8.6% each); with tazobactam it was the most frequent with aztreonam (53.4%), cefoperazone (44.8%) and cefepime (37.9%). No synergy was demonstrated after application of meropenem regardless of the kind of beta-lactamase inhibitor used. In 58 strains of S. maltophilia, 55 different profiles of DDST positivity were found. The results confirm that clavulanate is the most effective inhibitor of S. maltophilia beta-lactamases. The utilization of DDST (performed in the recommended way) for the typization of strains Stenotrophomonas species and for the estimation of potential effectiveness combinations of beta-lactams with beta-lactamase inhibitors for the therapy of stenotrophomonade infections was suggested.

Topics: Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactams; Drug Resistance, Bacterial; Drug Synergism; Enzyme Inhibitors; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Stenotrophomonas maltophilia; Sulbactam

We studied the effect of pH (7.1, 6.3, and 5.8) on the in vitro susceptibilities of 59 isolates of Bacteroides fragilis and 60 isolates of other B. fragilis group species to trovafloxacin, ciprofloxacin, clindamycin, ampicillin-sulbactam, piperacillin-tazobactam, imipenem, and meropenem. For each agent tested the geometric mean MIC was highest at pH 5.8, intermediate at pH 6.3, and lowest at pH 7.1. The magnitude of the pH effect varied greatly among different antibiotics. These data show that an acidic pH decreases the in vitro susceptibilities of the B. fragilis group to several antibiotics.

Topics: Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Bacteroides fragilis; Ciprofloxacin; Clindamycin; Drug Therapy, Combination; Fluoroquinolones; Hydrogen-Ion Concentration; Imipenem; Meropenem; Microbial Sensitivity Tests; Naphthyridines; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Thienamycins

The molecular basis of ceftazidime resistance in 2 isolates of Klebsiella pneumoniae was studied. The first (21300) expressed resistance to ceftazidime and piperacillin-tazobactam. The second (26139) expressed resistance to ceftazidime but remained susceptible to piperacillin-tazobactam. The 2 strains harbored similar large plasmids that hybridized to TEM- and SHV-related beta-lactamase genes. An Escherichia coli strain harboring the plasmid conferring resistance to both compounds (pLRM7) produced beta-lactamases of pI 5.9 (TEM-6) and pI 7.6 (SHV-1). E. coli harboring the other plasmid (pLRM8) expressed only the TEM enzyme because of insertion of IS15 within blaSHV-1. In vivo studies suggested that resistance to beta-lactam-beta-lactamase inhibitor combinations conferred by pLRM7 will be clinically important. Clinical resistance to both extended-spectrum cephalosporins and beta-lactam-beta-lactamase inhibitor combinations is achievable via the production of two enzymes, with only one possessing an extended spectrum of activity.

Topics: Abdominal Abscess; Amino Acid Sequence; Ampicillin; Animals; Base Sequence; beta-Lactamase Inhibitors; beta-Lactamases; Ceftazidime; Cephalosporin Resistance; Cephalosporins; DNA, Bacterial; Drug Therapy, Combination; Escherichia coli; Klebsiella Infections; Klebsiella pneumoniae; Molecular Biology; Molecular Sequence Data; Penicillanic Acid; Penicillin Resistance; Piperacillin; Piperacillin, Tazobactam Drug Combination; R Factors; Rats; Sulbactam

Mycobacterium tuberculosis and Mycobacterium leprae develop resistance against the drugs used to treat tuberculosis and leprosy, respectively. Now multidrug-resistant tuberculosis is spreading in many countries, especially with the emergence of AIDS. Multidrug treatment is being promoted at present to eradicate leprosy. Since M. leprae may also become multidrug-resistant, new approaches have to be adopted for controlling mycobacterial diseases. Mycobacteria usually synthesize beta-lactamase and are insensitive to beta-lactam antibiotics. M. tuberculosis contains a constitutive beta-lactamase; de-repression of beta-lactamase has been reported in M. leprae. Three different beta-lactam/beta-lactamase-inhibitor combinations (ampicillin/sulbactam, amoxicillin/clavulanate and piperacillin/tazobactam) were used to suppress the growth of several strains of mycobacteria (including M. tuberculosis H37Rv) in vitro. Ampicillin/sulbactam is a potent bactericidal agent against M. leprae multiplying in mouse foot pads. In the present work, ampicillin/sulbactam showed higher activity than the other drug combinations. The beta-lactam/beta-lactamase inhibitors are likely to be effective as rational therapeutic agents against mycobacterial infections.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Animals; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Clavulanic Acids; Drug Therapy, Combination; Mice; Microbial Sensitivity Tests; Mycobacterium; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam