Ceftazidime/Avibactam and Other Commonly Used Antibiotics Activity Against Enterobacterales and Pseudomonas aeruginosa Isolated in Poland in 2015-2019.

Purpose: Infections caused by resistant Gram-negative bacteria are becoming increasingly common and now pose a serious public health threat worldwide, because they are difficult to treat due to few treatment options and they are associated with high morbidity and mortality. The combination of ceftazidime with the beta-lactamase inhibitor avibactam - seems to be the right choice in this situation. The aim of the study was to evaluate the activity of ceftazidime/avibactam and other commonly used antibiotics against Enterobacterales and Pseudomonas aeruginosa strains isolated within last years in Poland. Patients and Methods: This study analyzed the antibiotic susceptibility of 1607 Enterobacterales isolates and 543 nonfermenting P. aeruginosa strains collected between 2015 and 2019 in 4 medical laboratories participating in the ATLAS (Antimicrobial Testing Leadership And Surveillance) program in Poland. Unduplicated clinically significant Enterobacterales and P. aeruginosa strains were collected from patients with respiratory, skin and musculoskeletal, genitourinary, abdominal, bloodstream or other infections (ear, eye). Results: The ceftazidime/avibactam combination demonstrates the highest activity against Enterobacterales (98.9%), in both adults and children, including strains presenting MDR (multidrug-resistant) (97.5%) and ESBL (extended spectrum ß-lactamase) (96.3%) phenotypes. The activity of ceftazidime/avibactam increased to 100% when only MBL (metallo-ß-lactamase)-negative subset of Enterobacterales was considered. This combination also achieved the second highest activity result (89.3%) after colistin in P. aeruginosa, including isolates of MDR (65.9%) and carbapenem-resistant (CR) phenotypes (54.8%). When MBL-positive isolates were excluded, susceptibility rate of P. aeruginosa increased to 94.7%. It is worth to note that susceptibility of the examined P. aeruginosa strains to ceftazidime/avibactam was very high in children (93.3%), especially in a pediatric intensive care unit (94.2%). Conclusion: Enterobacterales and P. aeruginosa included in this analysis presented high susceptibility rates to ceftazidime/avibactam. Ceftazidime/avibactam showed the highest activity against Enterobacterales strains among all antibiotics studied, both for the total population as well as for MDR phenotype and ESBL phenotype. Ceftazidime/avibactam also achieved the second highest activity result against P. aeruginosa strains (including MDR and CR phenotypes). These results are much higher when excluding MBL-positive isolates that exhibit intrinsic resistance to ceftazidime/avibactam.

In vitro activity of ceftazidime-avibactam and comparators against Enterobacterales and Pseudomonas aeruginosa isolates from Central Europe and Israel, 2014-2017 and 2018.

Between 2014 and 2017, 6,662 Enterobacterales and 1,953 P. aeruginosa isolates were collected by 19 centers in four central European countries and Israel. A further 2,585 Enterobacterales and 707 P. aeruginosa isolates were collected in 2018 by 28 centers in seven European countries and Israel as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) study. A central laboratory performed antimicrobial susceptibility testing using broth microdilution panels according to Clinical Laboratory Standards Institute (CLSI) guidelines. Susceptibility rates among Enterobacterales were highest to ceftazidime-avibactam (≥98.5%), colistin (≥97.3%), and meropenem (≥95.8%). Ceftazidime-resistant and multidrug-resistant (MDR) Enterobacterales subsets were highly susceptible to ceftazidime-avibactam (≥94.9%) and colistin (≥94.7%). Susceptibility rates to colistin among all P. aeruginosa were ≥97.4% and were ≥96.3% among ceftazidime-resistant and MDR subsets. Susceptibility rates to ceftazidime-avibactam were 91.9% (2014-2017), 86.3% (2018) and, in common with comparator agents, were lower among ceftazidime-resistant (≥51.7%) and MDR isolates (≥57.1%).

A phase II study of gemcitabine plus cisplatin in patients with advanced non-small cell lung cancer: clinical outcomes and quality of life.

The aim of the present phase II study was to assess the activity and safety of gemcitabine-cisplatin combination in advanced NSCLC, and to evaluate the impact of this regimen in terms of symptom benefit and quality of life (QOL). Eighty patients with pathologically confirmed advanced (stage IIIB and IV) NSCLC were enrolled into this study. Gemcitabine was administered on days 1, 8 and 15 at a dose of 1000 mg/m(2), and cisplatin was given on day 2 at a dose of 100 mg/m(2). The cycles were repeated every 4 weeks. The impact of treatment on QOL and on tumor-related symptoms was evaluated with the validated EORTC forms (QLQ-C30 and LC-13). The regimen was relatively well tolerated. Myelosuppresion was the principal toxicity. Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 58, 65 and 30% of patients respectively. In 143 cycles (35%) the administration of gemcitabine on day 15 was omitted due to myelosuppresion. Non-hematological toxicities were generally mild. Among the 76 patients available for response evaluation, there were 5 complete responses (7%) and 26 partial responses (34%); an overall response rate of 41%. The median duration of response was 8.0 months. The median survival for all 80 patients was 11.0 months and the actuarial 1-year survival probability 45%. During therapy global QOL improved in 22% of patients and particular functional domains increased in 19-37% of patients. Dyspnea was released in 36% of patients, fatigue in 45%, chest pain in 38%, shoulder pain in 27%, cough in 44%, and hemoptysis in 75%. The mean intensity scores of the last three symptoms decreased significantly with therapy. Our study confirmed relatively high efficacy of the gemcitabine-cisplatin combination in patients with advanced NSCLC. Of particular importance was that treatment with gemcitabine-cisplatin combination in a large proportion of patients was also associated with remarkable symptomatic release and with improvement of QOL. However, the high frequency of myelotoxicity-related gemcitabine omissions on day 15 of the cycle indicates that modification of the schedule should be considered in standard care.

Efficacy and safety of prandial premixed therapy using insulin lispro mix 50/50 3 times daily compared with progressive titration of insulin lispro mix 75/25 or biphasic insulin aspart 70/30 twice daily in patients with type 2 diabetes mellitus: a randomized, 16-week, open-label study.

BACKGROUND: Prandial premixed therapy 3 times daily has been proposed recently for type 2 diabetes mellitus (T2DM) patients who fail to achieve glycemic control with commonly used premixed insulin analogs, insulin lispro mix 75/25 (LM75/25) and biphasic insulin aspart 70/30 (BIAsp70/30) BID. OBJECTIVE: The aim of this work was to compare the efficacy and safety of 3-times daily insulin lispro mix 50/50 (TID group) with progressive titration of twice-daily LM75/25 or BIAsp70/30 (BID group) administered along with metformin in T2DM patients. METHODS: This was an open-label, 16-week, multicenter, randomized, parallel trial. End point glycosylated hemoglobin (HbA(1c)) was the primary efficacy measure; HbA(1c) reduction from baseline to end point, percentage of patients reaching target HbA(1c) (<7.0% and ≤6.5%), postprandial blood glucose (BG), and BG excursions after lunch were secondary measures. Safety was evaluated by collecting adverse events. RESULTS: A total of 302 patients with mean (SD) age 57.7 (9.27) years, diabetes duration 11.2 (6.47) years, HbA(1c) 8.5% (1.23), fasting BG 184.0 (53.04) mg/dL, body weight 86.8 (14.79) kg, body mass index 31.7 (4.23) kg/m(2), and daily insulin dose ∼48 IU were randomized. No significant difference was observed in end point HbA(1c) between the 2 groups. Seven-point BG profiles showed lower fasting and postbreakfast BG in the BID group but lower postlunch BG in the TID group. Daily insulin dose change was similar in both groups, with more weight gain in the TID group (P = 0.0009). Overall hypoglycemic rates were similar in both groups, but nocturnal hypoglycemia was more frequent in the BID group (P = 0.0063). CONCLUSIONS: In patients with T2DM who have not achieved adequate glycemic control with LM75/25 and BiAsp70/30 BID plus metformin and who are not candidates for basal bolus therapy, switching either to treatment with LM50/50 TID or to progressive titration of premix insulin analogs BID did not produce sufficient evidence of a difference of overall glycemic control between the 2 treatment groups. Short study duration and less intensive dose adjustments might have contributed to these results.

A comparative study of cefaclor vs amoxicillin/clavulanate in pediatric pharyngotonsillitis.

BACKGROUND: Pharyngotonsillitis (PT) caused by group A beta hemolytic streptococci (GABHS) is one of the most common infections of childhood. Two antibiotic suspensions, cefaclor (CEF) and amoxicillin/clavulanate (AMC), are commonly used in Poland for the treatment of PT caused by GABHS in children. MATERIAL/METHODS: This multi-center, randomized, single-blinded study was undertaken in order to compare the efficacy and safety of CEF (20 mg/kg/d) and AMC (25 mg/kg/d) in 10 days treatment of GABHS-related PT. 100 children (mean age 6 years) were enrolled into the study. Clinical and bacteriological assessments were done on the 14-18 th, and 38-45 th days after randomization. RESULTS: No GABHS strain isolated from throat smears was resistant in vitro to both antibiotics. Both antibiotics had almost 98% effectiveness at the post therapy visit. On follow-up, significantly more relapses and recurrences were observed in the AMC-treated group than in the CEF-treated group (relapse rate 21.28% vs 15.56%, p<0.02, recurrence 10.64% vs 6.66%, p<0.002). The relapse odds ratio in the AMC group was 1.7 times greater than in the CEF group, and recurrence was 1.5 times higher. There were significantly higher rates of gastrointestinal adverse events in children treated by AMC (p<0.02). CONCLUSIONS: CEF provides a clinically and bacteriologically effective treatment for children with PT caused by GABHS, comparable to AMC but significantly safer in terms of gastrointestinal side effects. AMC shows a greater risk of relapse and recurrence than CEF.