Immediate and later impacts of antimicrobial consumption on carbapenem-resistant Acinetobacter spp., Pseudomonas aeruginosa, and Klebsiella spp. in a teaching hospital in Brazil: a 10-year trend study.

To evaluate trends and the immediate and late impact of antimicrobial consumption on carbapenem-resistant Acinetobacter spp. (CRAs), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Klebsiella spp. (CRKs) over a 10-year period. An ecological study was conducted at the teaching hospital in São Paulo, Brazil, from 2007 to 2016. Consumption and resistance data were collected from the supply sector and central laboratory of the institution, respectively. Associations between consumption and resistance were analyzed in the same year, 1 year later, and 2 years later by linear regression of mixed effects. A total of 22,041 isolates were analyzed. Among these, 9988 corresponded to the gram-negatives in this study [3682 (36.9%) were Klebsiella spp., 3169 (31.7%) were P. aeruginosa, and 3137 (31.4%) were Acinetobacter spp.]. An increasing trend of consumption was observed, except for fourth-generation cephalosporins. Carbapenems were the most used antimicrobial class; CRKs presented a substantial increase over this period (from 1.4 to 67.0%; p = 0.001). Increased consumption of third-generation cephalosporins reduced CRAs [- 2.43%, 95% confidence interval (CI), - 3.30 to - 1.57; p < 0.001] and increased CRPA [26.67%, 95% CI, 2.99 to 50.35; p = 0.034] in the same year. Increased consumption of ß-lactam/ß-lactamase inhibitors increased CRKs with a 1-year delay [5.13%, 95% CI, 2.40 to 7.86; p = 0.001]. Our study demonstrated high antimicrobial consumption and growing carbapenem-resistance rates among gram-negative bacteria, especially Klebsiella spp., and the immediate and later effects of consumption of multiple antimicrobials on carbapenem resistance.

In vivo efficacy of a human-simulated regimen of ceftaroline combined with NXL104 against extended-spectrum-beta-lactamase (ESBL)-producing and non-ESBL-producing Enterobacteriaceae.

Ceftaroline exhibits in vitro activity against extended-spectrum ß-lactamase (ESBL)-, AmpC-, and KPC-producing Enterobacteriaceae when combined with the novel ß-lactamase inhibitor NXL104. The purpose of this study was to evaluate the efficacy of a human-simulated regimen of ceftaroline plus NXL104 against Enterobacteriaceae in a murine thigh infection model. Twelve Enterobacteriaceae isolates were tested with neutropenic ICR mice. Seven of these isolates were also tested with immunocompetent mice. Doses were given to simulate human free-drug exposures of ceftaroline (600 mg) plus NXL104 (600 mg) every 8 h over 24 h by targeting the percentage of time that free drug concentrations remain above the MIC, ƒT>MIC. The change in log(10) CFU/ml compared with 0 h controls was observed after 24 h. Human-simulated exposures were achieved against all isolates (MICs of ≤0.015 to 1 µg/ml) in both the neutropenic and the immunocompetent host models, which was equivalent to a ƒT>MIC of 100%. A 0.5 to ≥ 2 log CFU reduction was observed in the neutropenic thigh infection model. Furthermore, significantly greater reductions in bacterial density were observed for five of seven isolates studied in an immunocompetent model than in the neutropenic-host model. Regardless of immune status, ceftaroline (600 mg) combined with NXL104 (600 mg) every 8 h provided predictable efficacy against ESBL-, non-ESBL-, and KPC-producing isolates with an MIC of ≤ 1 µg/ml and could be useful in combating the growing threat of resistant Enterobacteriaceae.

Early switch/early discharge opportunities for hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections in Brazil.

BACKGROUND: Early antibiotic switch and early discharge protocols have not been widely studied in Latin America. Our objective was to describe real-world treatment patterns, resource use, and estimate opportunities for early switch from intravenous to oral antibiotics and early discharge for patients hospitalized with methicillin-resistant Staphylococcus aureus complicated skin and soft-tissue infections. MATERIALS/METHODS: This retrospective medical chart review recruited 72 physicians from Brazil to collect data from patients hospitalized with documented methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections between May 2013 and May 2015, and discharged alive by June 2015. Data collected included clinical characteristics and outcomes, hospital length of stay, methicillin-resistant Staphylococcus aureus-targeted intravenous and oral antibiotic use, and early switch and early discharge eligibility using literature-based and expert-validated criteria. RESULTS: A total of 199 patient charts were reviewed, of which 196 (98.5%) were prescribed methicillin-resistant Staphylococcus aureus -active therapy. Only four patients were switched from intravenous to oral antibiotics while hospitalized. The mean length of methicillin-resistant Staphylococcus aureus-active treatment was 14.7 (standard deviation, 10.1) days, with 14.6 (standard deviation, 10.1) total days of intravenous therapy. The mean length of hospital stay was 22.2 (standard deviation, 23.0) days. The most frequent initial methicillin-resistant Staphylococcus aureus-active therapies were intravenous vancomycin (58.2%), intravenous clindamycin (19.9%), and intravenous daptomycin (6.6%). Thirty-one patients (15.6%) were discharged with methicillin-resistant Staphylococcus aureus -active antibiotics of which 80.6% received oral antibiotics. Sixty-two patients (31.2%) met early switch criteria and potentially could have discontinued intravenous therapy 6.8 (standard deviation, 7.8) days sooner, and 65 patients (32.7%) met early discharge criteria and potentially could have been discharged 5.3 (standard deviation, 7.0) days sooner. CONCLUSIONS: Only 2% of patients were switched from intravenous to oral antibiotics in our study while almost one-third were early switch eligible. Additionally, one-third of hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections were early discharge eligible indicating opportunity for reducing intravenous therapy and days of hospital stay. These results provide insight into possible benefits of implementation of early switch/early discharge protocols in Brazil.

Molecular characterization of vancomycin-resistant Enterococci strains eight years apart from its first isolation in São Paulo, Brazil.

E. faecium was the first reported VRE species, carrying the vanA gene in Brazil. In spite of this, vancomycin-resistant E. faecalis has become the predominant species in Brazilian hospitals. The aim of this study was to evaluate the genetic relatedness of VREs isolated in a Brazilian teaching hospital eight years apart from its first isolation. We analyzed 38 VRE strains obtained from 81 surveillance cultures of patients admitted to the four largest intensive care units in Hospital São Paulo in February, 2006. Presence of the vanA gene was assayed by PCR and PFGE analysis was used for molecular characterization. All VRE strains carried the vanA gene. Two distinct clonal groups were observed among vancomycin-resistant E. faecalis. Vancomycin-resistant E. faecium belonged to five distinct clones were demonstrated by molecular typing. All of these clones were different from the first vancomycin-resistant enterococci clone isolated eight years ago in our hospital.

Assessment of healthcare professionals' adherence to hand hygiene after alcohol-based hand rub introduction at an intensive care unit in São Paulo, Brazil.

We analyzed the impact of introducing an alcohol-based hand gel and an educational program on hand hygiene adherence among healthcare workers in an intensive care unit. Adherence to hand hygiene was significantly higher after the intervention for the night shift work period (P=.001), among nursing assistants (P=.001), among nurses (P=.007) on weekend days (P=.016), and for invasive procedures (P=.012).

Compliance with handwashing at two intensive care units in São Paulo.

Handwashing compliance was compared at two medical- surgical intensive care units (ICUs) of a teaching and a non-teaching hospital. The mean compliance was 22.2% and 42.6%, respectively. Respiratory therapists at the non-teaching hospital had the best handwashing compliance (52.6%). Nursing assistants at the teaching hospital had the worst compliance (11.5%). Nursing assistant was the only health-care worker category with a significant difference between the two ICUs (odds ratio = 6.0; 95% confidence interval = 3.83-9.43; p< 0.001).

Catheter-associated urinary tract infection after cardiovascular surgery: Impact of a multifaceted intervention.

BACKGROUND: The aims of this study were to assess the impact of a multifaceted intervention on the incidence of catheter-associated urinary tract infection (CAUTI) and on the urinary catheter utilization (UCU) ratio, evaluating adherence to recommendations for the use of indwelling urinary catheters (IUCs). METHODS: This prospective, before-and-after interventional study was conducted in three 6-month phases: preintervention (phase 1), intervention (phase 2), and postintervention (phase 3). We observed IUC insertion technique, maintenance care, and removal/nonremoval practices; provided training on CAUTI prevention measures; evaluated professional knowledge; provided adherence feedback; determined the incidence of CAUTI, and calculating the UCU ratio. RESULTS: Between phases 1 and 3, CAUTI incidence fell from 11.42 to 4.40 cases/1000 catheter-days (P = .216), whereas the UCU ratio remained constant. The risk of CAUTI was 2.6-fold higher in phase 1 than in phase 3. Adherence to hand hygiene (before and after IUC insertion) improved significantly, as did adherence to attaching the IUC to the patient and maintenance care guidelines. The reasons for IUC use (including inappropriate reasons) did not differ significantly. Professional knowledge improved significantly after training. CONCLUSION: A multifaceted intervention effectively reduced CAUTI incidence and improved the quality of care.

Impact of an Automated Surveillance to Detect Surgical-Site Infections in Patients Undergoing Total Hip and Knee Arthroplasty in Brazil.

In this retrospective study, we compared automated surveillance with conventional surveillance to detect surgical site infection after primary total hip or knee arthroplasty. Automated surveillance demonstrated better efficacy than routine surveillance in SSI diagnosis, sensitivity, and predictive negative value in hip and knee arthroplasty. Infect Control Hosp Epidemiol 2016;37:991-993.

Trueperella bernardiae: first report of wound infection post laparoscopic surgery.

We report the first case of wound infection caused by Trueperella bernardiae after laparoscopic surgery. The patient was treated with oral amoxicillin/clavulanate which was continued for 1 week after discharge with a successful clinical response. There are few cases described but none related to wound infection after laparoscopic surgery.

The changing epidemiology of Acinetobacter spp. producing OXA carbapenemases causing bloodstream infections in Brazil: a BrasNet report.

We evaluated the epidemiology of Acinetobacter spp. recovered from patients diagnosed with bloodstream infections in 9 tertiary hospitals located in all Brazilian geographic regions between April and August 2014. Although OXA-23-producing Acinetobacter baumannii clones were disseminated in most hospitals, it was observed for the first time the spread of OXA-72 among clonally related A. baumannii isolated from distinct hospitals. Interestingly, Acinetobacter pittii was the most frequent species found in a Northern region hospital. Contrasting with the multisusceptible profile displayed by A. pittii isolates, the tetracyclines and polymyxins were the only antimicrobials active against all A. baumannii isolates.

Early switch/early discharge opportunities for hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections in Brazil

ABSTRACT Background: Early antibiotic switch and early discharge protocols have not been widely studied in Latin America. Our objective was to describe real-world treatment patterns, resource use, and estimate opportunities for early switch from intravenous to oral antibiotics and early discharge for patients hospitalized with methicillin-resistant Staphylococcus aureus complicated skin and soft-tissue infections. Materials/methods: This retrospective medical chart review recruited 72 physicians from Brazil to collect data from patients hospitalized with documented methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections between May 2013 and May 2015, and discharged alive by June 2015. Data collected included clinical characteristics and outcomes, hospital length of stay, methicillin-resistant Staphylococcus aureus-targeted intravenous and oral antibiotic use, and early switch and early discharge eligibility using literature-based and expert-validated criteria. Results: A total of 199 patient charts were reviewed, of which 196 (98.5%) were prescribed methicillin-resistant Staphylococcus aureus -active therapy. Only four patients were switched from intravenous to oral antibiotics while hospitalized. The mean length of methicillin-resistant Staphylococcus aureus-active treatment was 14.7 (standard deviation, 10.1) days, with 14.6 (standard deviation, 10.1) total days of intravenous therapy. The mean length of hospital stay was 22.2 (standard deviation, 23.0) days. The most frequent initial methicillin-resistant Staphylococcus aureus-active therapies were intravenous vancomycin (58.2%), intravenous clindamycin (19.9%), and intravenous daptomycin (6.6%). Thirty-one patients (15.6%) were discharged with methicillin-resistant Staphylococcus aureus -active antibiotics of which 80.6% received oral antibiotics. Sixty-two patients (31.2%) met early switch criteria and potentially could have discontinued intravenous therapy 6.8 (standard deviation, 7.8) days sooner, and 65 patients (32.7%) met early discharge criteria and potentially could have been discharged 5.3 (standard deviation, 7.0) days sooner. Conclusions: Only 2% of patients were switched from intravenous to oral antibiotics in our study while almost one-third were early switch eligible. Additionally, one-third of hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections were early discharge eligible indicating opportunity for reducing intravenous therapy and days of hospital stay. These results provide insight into possible benefits of implementation of early switch/early discharge protocols in Brazil.

Assessing the pharmacodynamic profile of intravenous antibiotics against prevalent Gram-negative organisms collected in Colombia.

OBJECTIVES: This study was designed to simulate standard and optimized dosing regimens for intravenous antibiotics against contemporary populations of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa using MIC distribution data to determine which of the tested carbapenem regimens provided the greatest opportunity for obtaining maximal pharmacodynamic (PD) activity. METHODS: The isolates studied were obtained from the COMPACT-COLOMBIA surveillance program conducted between February and November 2009. Antimicrobial susceptibility testing was conducted by broth microdilution method according to the CLSI guidelines. Doripenem, imipenem-cilastatin, and meropenem, were the modeled antibiotics. A 5,000 patient Monte Carlo simulation was performed for each regimen and PD targets were defined as free drug concentrations above the MIC for at least 40% of the dosing interval. RESULTS: All carbapenem regimens obtained optimal exposures against E. coli, unlike the other Enterobacteriaceae tested. Against P. aeruginosa, only a prolonged infusion of doripenem exceeded the 90% cumulative fraction of response (CFR) threshold. Worrisomely, no regimens for any of the drugs tested obtained optimal CFR against A. baumannii. For P. aeruginosa intensive care unit (ICU) isolates, CFR was approximately 20% lower for isolates collected in the respiratory tract compared with bloodstream or intra-abdominal for imipenem and meropenem. Noteworthy, all doripenem and meropenem regimens achieved greater than 90% CFR against bloodstream and respiratory isolates of K. pneumoniae. CONCLUSIONS: Our data suggests that higher dosing and prolonged infusion of doripenem or meropenem may be suitable for empirically treating ICU P. aeruginosa, while none of the carbapenems achieved optimal cumulative fraction of response against A. baumannii. Standard dosing regimens of all the carbapenems tested achieved optimal CFR against E. coli isolates, but higher carbapenem dosages might be required for empiric treatment of K. pneumoniae, particularly from an intra-abdominal source. Non-standard dosage regimens studied in this modeling should be proven effective in prospective clinical trials.

Overview perspective of bacterial resistance.

The rapidly escalating prevalence of antimicrobial resistance is a global concern. This reduced susceptibility to currently available antimicrobial agents coupled with the progressive shortage of newly approved compounds is a worrisome situation. Major problems are encountered for a growing number of Gram-positive (i.e., Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus spp.) and Gram-negative pathogens (i.e., Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae). We provide an overview of bacterial resistance focusing on the most common pathogens responsible for infection in both the community and healthcare settings. In addition, several strategies to curb antimicrobial resistance are also discussed. It is increasingly evident that without the introduction of novel antimicrobial agents, a return to the clinical outcomes associated with the pre-antibiotic era are inevitable.

Imipenem-resistant Pseudomonas aeruginosa infection at a medical-surgical intensive care unit: risk factors and mortality.

OBJECTIVES: The aim of this study was to evaluate the risk factors and attributable mortality associated with imipenem-resistant Pseudomonas aeruginosa (IRPA) infections in a medical-surgical intensive care unit (ICU). METHODS: A retrospective case-control study was carried out at a 16-bed medical-surgical ICU in a 780-bed, university-affiliated hospital. All patients admitted from January 1, 2003, to December 31, 2004, who had nosocomial infection caused by IRPA, were included in the study. RESULTS: Imipenem-resistant P. aeruginosa was recovered from 63 patients during the study period. One hundred eighty-two controls were matched with cases by period of admission, age, and time at risk. Urinary tract (34.9%) and respiratory tract (22.2%) were the main sources of IRPA isolation. In multivariate analysis, a previous stay in the ICU (odds ratio, 3.54; 95% confidence interval [CI], 1.29-9.73; P = .03) was the only independent risk factor for IRPA infection. The in-hospital mortality rate among case patients was 49% (31 of 63) compared with 33% (61 of 182) for control patients (odds ratio, 1.92; 95% CI, 1.07-3.44; P = .02). Thus, we had an attributable mortality of 16% (95% CI, 9.74%-22.3%; P = .03). CONCLUSIONS: Our study suggests that IRPA infections are strongly related to previous ICU stay, and that IRPA infections significantly increase mortality in those critical patients.

Impact of an education program on the incidence of central line-associated bloodstream infection in 2 medical-surgical intensive care units in Brazil.

An intervention study was undertaken to evaluate the impact of an education program on the incidence of central line-associated bloodstream infection (CLABSI) in 2 intensive care units. There was a nonsignificant reduction in the incidence of CLABSI (odds ratio, 0.46 [95% confidence interval, 0.21-1.02]; P=.04) despite a significant increase in knowledge of CLABSI prevention by the staff of both intensive care units after the education program.

Impact of a hospital-wide antimicrobial formulary intervention on the incidence of multidrug-resistant gram-negative bacteria.

We examined the impact of an antimicrobial formulary change, based on reduction in third-generation cephalosporin use, on resistant gram-negative pathogens in a tertiary hospital. No significant changes were demonstrated in their incidence per 1000 patient-days. Otherwise, there was a significant decrease in rate of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (63.1% to 52.5%, P = .04) and third-generation cephalosporin-resistant Enterobacter species (31.4% to 25%, P = .04) between the 2 study periods. On the other hand, there was also a significant increase in rate of ampicillin-sulbactam-resistant Acinetobacter baumannii (8% to 47%, P = .01) after the implementation of the formulary intervention.

Assessing the pharmacodynamic profile of intravenous antibiotics against prevalent Gram-negative organisms collected in Colombia

OBJECTIVES: This study was designed to simulate standard and optimized dosing regimens for intravenous antibiotics against contemporary populations of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa using MIC distribution data to determine which of the tested carbapenem regimens provided the greatest opportunity for obtaining maximal pharmacodynamic (PD) activity. METHODS: The isolates studied were obtained from the COMPACT-COLOMBIA surveillance program conducted between February and November 2009. Antimicrobial susceptibility testing was conducted by broth microdilution method according to the CLSI guidelines. Doripenem, imipenem-cilastatin, and meropenem, were the modeled antibiotics. A 5,000 patient Monte Carlo simulation was performed for each regimen and PD targets were defined as free drug concentrations above the MIC for at least 40 percent of the dosing interval. RESULTS: All carbapenem regimens obtained optimal exposures against E. coli, unlike the other Enterobacteriaceae tested. Against P. aeruginosa, only a prolonged infusion of doripenem exceeded the 90 percent cumulative fraction of response (CFR) threshold. Worrisomely, no regimens for any of the drugs tested obtained optimal CFR against A. baumannii. For P. aeruginosa intensive care unit (ICU) isolates, CFR was approximately 20 percent lower for isolates collected in the respiratory tract compared with bloodstream or intra-abdominal for imipenem and meropenem. Noteworthy, all doripenem and meropenem regimens achieved greater than 90 percent CFR against bloodstream and respiratory isolates of K. pneumoniae. CONCLUSIONS: Our data suggests that higher dosing and prolonged infusion of doripenem or meropenem may be suitable for empirically treating ICU P. aeruginosa, while none of the carbapenems achieved optimal cumulative fraction of response against A. baumannii. Standard dosing regimens of all the carbapenems tested achieved optimal CFR against E. coli isolates, but higher carbapenem dosages might be required for empiric treatment of K. pneumoniae, particularly from an intra-abdominal source. Non-standard dosage regimens studied in this modeling should be proven effective in prospective clinical trials.