Determination of MIC and Disk Diffusion Quality Control Guidelines for Meropenem–Vaborbactam, a Novel Carbapenem/Boronic Acid β-Lactamase Inhibitor Combination

Meropenem–vaborbactam is a carbapenem/cyclic boronic acid β-lactamase inhibitor combination primarily active against Gram-negative bacilli, including those harboring class A serine carbapenemases such as Klebsiella pneumoniae carbapenemase (KPC). A Clinical and Laboratory Standards Institute M23-A4 (Tier 2) quality control study established broth microdilution and disk diffusion ranges for reference strains. Two KPC-producing K. pneumoniae ATCC strains are recommended for quality control testing

Ceftaroline activity tested against contemporary Latin American bacterial pathogens (2011)

AbstractA total of 2484 target bacterial pathogens were collected (one per patient episode) from patients in 16 Latin American medical centers located in seven nations during 2011. Isolate identity was confirmed at a coordinating laboratory and susceptibility testing was performed for ceftaroline and comparator agents according to reference broth microdilution methods. A total of 30.0% of isolates were from respiratory tract, 29.4% from skin and skin structure, 21.4% from blood stream, 7.9% from urinary tract and 11.3% from other sites. Ceftaroline was active against Staphylococcus aureus (42.8% MRSA) with 83.6% of the isolates at ≤1mg/L and all isolates at ≤2mg/L (MIC5090, 0.25/2mg/L). National MRSA rates ranged from a low of 28.8% in Colombia to a high of 68.1% in Chile. All Streptococcus pyogenes and Streptococcus agalactiae were susceptible to ceftaroline (MIC50/90 values were at ≤0.015/≤0.015mg/L for both). All Streptococcus pneumoniae were susceptible to ceftaroline, linezolid, tigecycline and vancomycin. Susceptibility to ceftriaxone was at 88.4% (CLSI non-meningitis interpretive criteria) and 73.9% (CLSI meningitis interpretive criteria) for all S. pneumoniae. Ceftriaxone susceptibility was only at 33.3% (CLSI non-meningitis interpretive criteria) and 0.0% (CLSI meningitis interpretive criteria) for penicillin-intermediate (penicillin MIC, 4mg/L) strains. All Haemophilus influenzae (29.4% β-lactamase-positive) isolates were susceptible to ceftaroline, amoxicillin–clavulanate, ceftriaxone, and levofloxacin. For the Latin American region, the ESBL-phenotype rate was 37.6% for Escherichia coli and 53.3% for Klebsiella pneumoniae. Ceftaroline was not active against ESBL-phenotype strains but was active against >90.0% of the non-ESBL-phenotype. The spectrum of activity of ceftaroline against pathogens from Latin America indicates that it merits further study for its potential use in the Latin American region

Ceftobiprole Activity against over 60,000 Clinical Bacterial Pathogens Isolated in Europe, Turkey, and Israel from 2005 to 2010

Ceftobiprole medocaril is a newly approved drug in Europe for the treatment of hospital-acquired pneumonia (HAP) (excluding patients with ventilator-associated pneumonia but including ventilated HAP patients) and community-acquired pneumonia in adults. the aim of this study was to evaluate the in vitro antimicrobial activity of ceftobiprole against prevalent Gram-positive and -negative pathogens isolated in Europe, Turkey, and Israel during 2005 through 2010. A total of 60,084 consecutive, nonduplicate isolates from a wide variety of infections were collected from 33 medical centers. Species identification was confirmed, and all isolates were susceptibility tested using reference broth microdilution methods. Ceftobiprole had high activity against methicillin-susceptible Staphylococcus aureus (MSSA) (100.0% susceptible), methicillin-susceptible coagulase-negative staphylococci (CoNS), beta-hemolytic streptococci, and Streptococcus pneumoniae (99.3% susceptible), with MIC90 values of 0.25, 0.12, 80% inhibited at 8 mu g/ml; 64.6% at MIC values of 16 mu g/ml; 75.4% susceptible), but limited activity was observed against Acinetobacter spp. and Stenotrophomonas maltophilia. High activity was also observed against all Haemophilus influenzae (MIC90, <= 0.06 mu g/ml) and Moraxella catarrhalis (MIC50/90, <= 0.06/0.25 mu g/ml) isolates. Ceftobiprole demonstrated a wide spectrum of antimicrobial activity against this very large longitudinal sample of contemporary pathogens.Basilea Pharmaceutica International AG (Basel, Switzerland)AchaogenAiresAmerican Proficiency Institute (API)AnacorAstellasAstraZenecaBayerbioMerieuxCempraCerexaContrafectCubist PharmaceuticalsDaiichiDipexiumEnantaFuriexGlaxoSmithKlineJohnson JohnsonLegoChem Biosciences Inc.Meiji Seika KaishaMerckNabrivaNovartisParatekPfizerPPD TherapeuticsPremier Research GroupRempexRib-X PharmaceuticalsSeachaidShionogiThe Medicines Co.TheravanceThermo FisherJMI Labs, North Liberty, IA 52317 USAUniv Toronto, Dept Lab Med & Pathobiol, Toronto, ON, CanadaUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilTufts Univ, Sch Med, Boston, MA 02111 USAUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilWeb of Scienc

Telavancin activity when tested by a revised susceptibility testing method against uncommonly isolated Gram-positive pathogens responsible for documented infections in hospitals worldwide (2011–2013)

AbstractThe broth microdilution method for telavancin susceptibility testing was revised and now utilises DMSO as solvent for stock solution preparation and diluent for stock solution dilution, following CLSI guidelines for water-insoluble agents. The revised method also incorporates polysorbate 80 in the test medium to mitigate drug binding to plastics. This revised methodology provides more accurate and reproducible MIC determinations, which results in values lower than the previously established method. This study was conducted to re-establish telavancin potencies and susceptibility profiles (using updated interpretive criteria) against a collection of uncommon clinical pathogens (3821 isolates). Telavancin showed MIC50 values of 0.06mg/L against tested staphylococcal species (MIC50/90, 0.03/0.06mg/L; 98.1–100.0% susceptible), with lower results for Staphylococcus hominis (MIC50, ≤0.015mg/L), Staphylococcus lugdunensis (MIC50, ≤0.015mg/L) and Staphylococcus simulans (MIC50, 0.03mg/L). Vancomycin (MIC50, 1mg/L), daptomycin (MIC50, 0.12–1mg/L) and linezolid (MIC50, 0.25–1mg/L) had MIC50 results at least four-fold higher than telavancin against CoNS. Streptococci (99.2–100.0% susceptible) displayed telavancin MIC50 values of ≤0.015–0.03mg/L. Vancomycin (MIC50, 0.25–0.5mg/L) and linezolid (MIC50, 0.5–1mg/L) had higher MIC50 results against streptococci, whilst daptomycin MIC50 values varied from ≤0.06mg/L to 0.5mg/L. Micrococcus, Listeria and Corynebacterium spp. were inhibited by telavancin at ≤0.015, ≤0.03 and ≤0.06mg/L, respectively. Telavancin exhibited potent in vitro activity against this collection, greater than comparators (daptomycin, linezolid, vancomycin). This study provides new baseline MIC results for telavancin and confirms the spectrum and potency of telavancin against less commonly encountered Gram-positive species

Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease

BACKGROUND & AIMS: There are no effective and safe treatments for chronic hepatitis C virus (HCV) infection of patients who have advanced liver disease. METHODS: In this phase 2, open-label study, we assessed treatment with the NS5A inhibitor ledipasvir, the nucleotide polymerase inhibitor sofosbuvir, and ribavirin in patients infected with HCV genotypes 1 or 4. Cohort A enrolled patients with cirrhosis and moderate or severe hepatic impairment who had not undergone liver transplantation. Cohort B enrolled patients who had undergone liver transplantation: those without cirrhosis; those with cirrhosis and mild, moderate, or severe hepatic impairment; and those with fibrosing cholestatic hepatitis. Patients were assigned randomly (1:1) to receive 12 or 24 weeks of a fixed-dose combination tablet containing ledipasvir and sofosbuvir, once daily, plus ribavirin. The primary end point was sustained virologic response at 12 weeks after the end of treatment (SVR12). RESULTS: We enrolled 337 patients, 332 (99%) with HCV genotype 1 infection and 5 (1%) with HCV genotype 4 infection. In cohort A (nontransplant), SVR12 was achieved by 86%-89% of patients. In cohort B (transplant recipients), SVR12 was achieved by 96%-98% of patients without cirrhosis or with compensated cirrhosis, by 85%-88% of patients with moderate hepatic impairment, by 60%-75% of patients with severe hepatic impairment, and by all 6 patients with fibrosing cholestatic hepatitis. Response rates in the 12- and 24-week groups were similar. Thirteen patients (4%) discontinued the ledipasvir and sofosbuvir combination prematurely because of adverse events; 10 patients died, mainly from complications related to hepatic decompensation. CONCLUSION: The combination of ledipasvir, sofosbuvir, and ribavirin for 12 weeks produced high rates of SVR12 in patients with advanced liver disease, including those with decompensated cirrhosis before and after liver transplantation. ClinTrials.gov: NCT01938430

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat