Staphylococcus aureus is a microorganism frequently associated with implant-related infections, owing to its ability to produce biofilms. These infections are difficult to treat because antimicrobials must cross the biofilm to effectively inhibit bacterial growth. Although some antibiotics can penetrate the biofilm and reduce the bacterial load, it is important to understand that the results of routine sensitivity tests are not always valid for interpreting the activity of different drugs. In this review, a broad discussion on the genes involved in biofilm formation, quorum sensing, and antimicrobial activity in monotherapy and combination therapy is presented that should benefit researchers engaged in optimizing the treatment of infections associated with S. aureus biofilms.

Purpose: Antimicrobial stewardship programs are important for reducing antimicrobial resistance because they can readjust antibiotic prescriptions to local guidelines, switch intravenous to oral administration, and reduce hospitalization times. Pharmacokinetics–pharmacodynamics (PK-PD) empirically based prescriptions and therapeutic drug monitoring (TDM) programs are essential for antimicrobial stewardship, but there is a need to fit protocols according to cost benefits. The cost benefits can be demonstrated by reducing toxicity and hospital stay, decreasing the amount of drug used per day, and preventing relapses in infection. Our aim was to review the data available on whether PK-PD empirically based prescriptions and TDM could improve the cost benefits of an antimicrobial stewardship program to decrease global hospital expenditures. Methods: A narrative review based on PubMed search with the relevant studies of vancomycin, aminoglycosides, beta-lactams, and voriconazole. Results: TDM protocols demonstrated important cost benefit for patients treated with vancomycin, aminoglycosides, and voriconazole mainly due to reduce toxicities and decreasing the hospital length of stay. In addition, PK-PD strategies that used infusion modifications to meropenem, piperacillin-tazobactam, ceftazidime, and cefepime, such as extended or continuous infusion, demonstrated important cost benefits, mainly due to reducing daily drug needs and lengths of hospital stays. Conclusions: TDM protocols and PK-PD empirically based prescriptions improve the cost-benefits and decrease the global hospital expenditures.

Daptomycin has been used in bone and joint infections (BJI) and prosthesis joint infections (PJI) considering spectrum of activity and biofilm penetration. However, the current experience is based on case reports, case series, cohorts, and international surveys. The aim of this systematic review was to evaluate studies about daptomycin treatment efficacy in BJI/PJI compared to other antibiotic regimens. PubMed, LILACS, Scielo and Web of Science databases were searched for articles about daptomycin and treatment of BJI and PJI from inception to March 2018. Inclusion criteria were any published researches that included patients with BJI treated with daptomycin. Diagnosis of BJI was based on clinical, laboratory and radiological findings according to IDSA guidelines. From 5107 articles, 12 articles were included. Only three studies described the outcomes of patients with BJI treated with daptomycin with comparator regimen (vancomycin, teicoplanin and oxacillin). Studies presented large heterogeneity regarding device related infections, surgical procedures, and daptomycin regimens (varied from 4 mg/kg to 10 mg/kg). A total of 299 patients have been included in all studies (184 infections associated with orthopedic disposal and 115 osteomyelitis/septic arthritis). Two hundred and thirty-three patients were treated with daptomycin. The clinical cure rates on device related and non-device related infections (i.e. osteomyelitis) were 70% and 78%, respectively. Compared to all regimens evaluated, daptomycin group outcomes were non-inferior. Although a randomized clinical trial is needed, this systematic review tends to support daptomycin usage for bone and joint infections.

Antimicrobial stewardship programs are an efficient way to reduce inappropriate use of antimicrobials and costs; however, supporting data are scarce in middle-income countries. The aim of this study was to evaluate antibiotic use, bacterial susceptibility profiles, and the economic impact following implementation of a broad-spectrum beta-lactam-sparing antimicrobial stewardship program. An interrupted time-series analysis was performed to evaluate antibiotic use and expenditure over a 24-month period (12 months before the antimicrobial stewardship program and in the 12 months after implementation of the antimicrobial stewardship program). Antibiotics were classified into one of two groups: beta-lactam antibiotics and beta-lactam-sparing antibiotics. We also compared the antimicrobial susceptibility profiles of key pathogens in each period. Beta-lactam antibiotics use decreased by 43.04 days of therapy/1000 patient-days (p=0.04) immediately following antimicrobial stewardship program implementation, whereas beta-lacta-sparing antibiotics use increased during the intervention period (slope change 6.17 days of therapy/1000 patient-days, p<0.001). Expenditure decreased by $2089.99 (p<0.001) immediately after intervention and was maintained at this level over the intervention period ($-38.45; p=0.24). We also observed that a greater proportion of pathogens were susceptible to cephalosporins and aminoglycosides after the antimicrobial stewardship program. The antimicrobial stewardship program significantly reduced the use of broad-spectrum beta-lactam-antibiotics associated with a decrease in expenditure and maintenance of the susceptibility profile in Gram-negative bacteria.

Consumption of carbapenem has increased due to extended-spectrum beta-lactamase-producing bacteria spreading. Ertapenem has been suggested as a not carbapenem-resistance inducer. We performed a scoping review of carbapenem-sparing stewardship with ertapenem and its impact on the antibiotic resistance of Gram-negative bacilli. We searched PubMed for studies that used ertapenem as a strategy to reduce resistance to carbapenems and included epidemiologic studies with this strategy to evaluate susceptibility patterns to cephalosporins, quinolones, and carbapenems in Gram-negative-bacilli. The search period included only studies in English, up to February 2018. From 1294 articles, 12 studies were included, mostly from the Americas. Enterobacteriaceae resistance to quinolones and cephalosporins was evaluated in 6 studies and carbapenem resistance in 4 studies. Group 2 carbapenem (imipenem/meropenem/doripenem) resistance on A. baumannii was evaluated in 6 studies. All studies evaluated P. aeruginosa resistance to Group 2 carbapenem. Resistance profiles of Enterobacteriaceae and P. aeruginosa to Group 2 carbapenems were not associated with ertapenem consumption. The resistance rate of A. baumannii to Group 2 carbapenems after ertapenem introduction was not clear due to a lack of studies without bias. In summary, ertapenem as a strategy to spare use of Group 2 carbapenems may be an option to stewardship programs without increasing resistance of Enterobacteriaceae and P. aeruginosa. More studies are needed to evaluate the influence of ertapenem on A. baumannii.