OBJECTIVE: To develop a simple evaluation tool to assess methodologic rigor of the literature on patient compliance with medications, and to apply the tool to a sample of the literature. METHODS: A computerized search of the MEDLINE database (January 1980–December 1996) was performed. All English-language articles on compliance with medications were identified, using the MeSH terms patient-compliance and drug-therapy. A 10% sample was then randomly selected for review. Methodologic rigor was assessed on eight standards: study design, specification of patient sample, power analysis, specification of disease, specification of therapeutic regimen, duration of follow-up, definition of compliance, and compliance measurement. The raw scores of the eight standards were then combined in three summary scores, standardized from 0 to 100: study design, disease-related features, and compliance issues. RESULTS: Seventy-two articles from 719 identified were reviewed. The majority of the research articles were descriptive (63.9%), and patients in these studies were selected mainly from a convenience sample (41.7%). Just nine studies were multicenter studies, and three employed power analysis. The compliance definition was replicable in 41.7% of the studies. In 22 articles neither the compliance measure nor the criteria were stated. One-quarter of the studies (18) used a nonvalidated measure of compliance. Only two studies reached a score of 6 in the compliance measure, and eight studies used two different measures of compliance simultaneously. The median values in the summary scores were: study design 8.3, disease 42.9, compliance issues 50. CONCLUSIONS: The quality of the compliance research was generally poor. These low scores reflect very important shortcomings in the methodology. Such oversights make it difficult for the reader to critically assess the validity of the conclusions.

OBJECTIVE: To determine which factors affect compliance with sulfonylureas in a population served by a health maintenance organization in Southern California. METHODS: Retrospective analysis of pharmacy records and healthcare utilization data for two years (April 1993–March 1995), and a survey mailed to patients. Patients treated with sulfonylureas were selected for analysis on the basis of their prescription profile. Compliance was measured from the pharmacy records as the proportion of days the patient was in possession of the prescribed medications. Patient compliance with sulfonylureas was modeled as a function of four clusters of determinants: patient-related attributes, drug regimen characteristics and complexity, health status and disease-related variables, and characteristics of the interaction with healthcare providers. RESULTS: 786 patients were identified for analysis (49.1% women, mean age 59 y). The mean compliance rate was 83% ± 22% SD. Compliance was significantly positively related with age and self-reported level of medication-taking compliance at baseline. Factors shown to have an inverse relationship with compliance were treatment complexity, perception of general health, and being a newly treated patient (adjusted R ² for the final model = 0.148). CONCLUSIONS: Our results suggest that factors found to be associated with noncompliant behavior (e.g., being a newly treated patient, self-reported compliance, regimen complexity) can be assessed by physicians and pharmacists as a routine practice.

Background. Molnupiravir (MOL) and nirmatrelvir/ritonavir (NIR) were recently approved for the early treatment of COVID-19, but real-life data on tolerability, safety, and adverse events (AEs) are still scarce. Methods. We conducted a retrospective cohort study including all patients who were prescribed MOL and NIR at the Infectious Diseases Unit of Padua University Hospital, between January and May 2022. Demographic, clinical, and safety variables were recorded. Results. We included 909 patients, 48.3% males and 95.2% vaccinated against SARS-CoV-2. The median age was 73 (IQR: 62–82) years. MOL and NIR were prescribed in 407 (44.8%) and 502 (55.2%) patients, respectively. Overall, 124/909 (13.6%) patients experienced any AEs following antivirals intake: 98/124 (79%) patients reporting adverse events presented grade 1 AEs, 23/124 (18.5%) grade 2 AEs and 3 (2.5%) grade 3 AEs. Treatment discontinuation was recorded in 4.8% of patients. AEs were significantly higher in women, in patients treated with NIR compared to MOL and in people who were not vaccinated. Conclusions. In our real-life setting, AEs were higher than those reported by clinical trials, and were particularly associated with NIR use and with not being vaccinated. Further analyses are needed to better assess safety of oral antivirals and to define which patient’s profile may benefit most from MOL and NIR.

Background. A large increase in multi-drug-resistant Acinetobacter baumannii, especially carbapenem-resistant strains, occurred during the first two years of the COVID-19 pandemic, posing important challenges in its treatment. Cefiderocol appeared to be a good option for the treatment of Carbapenem-resistant Acinetobacter baumannii (CR-Ab), but to date, the guidelines and evidence available are conflicting. Methods. We retrospectively included a group of patients with CR-Ab infections (treated with colistin- or cefiderocol-based regimens) at Padua University Hospital (August 2020–July 2022) and assessed predictors of 30-day mortality, and differences in microbiological and clinical treatment. To evaluate the difference in outcomes, accounting for the imbalance in antibiotic treatment allocation, a propensity score weighting (PSW) approach was adopted. Results. We included 111 patients, 68% males, with a median age of 69 years (IQR: 59–78). The median duration of antibiotic treatment was 13 days (IQR:11–16). In total, 60 (54.1%) and 51 (45.9%) patients received cefiderocol- and colistin-based therapy, respectively. Notably, 53 (47.7%) patients had bloodstream infections, while 58 (52.3%) had pneumonia. Colistin was combined in 96.1%, 80.4%, and 5.8% of cases with tigecycline, meropenem, and fosfomycin, respectively. Cefiderocol was combined in 13.3%, 30%, and 18.3% of cases with fosfomycin, tigecycline, and meropenem, respectively. At the baseline, the two treatment groups significantly differed in age (patients treated with colistin were significantly older), the prevalence of diabetes and obesity (more frequent in the group treated with colistin), length of stay (longer in the group receiving cefiderocol), and type of infection (BSI were more frequent in the group receiving cefiderocol). The proportion of patients who developed acute kidney injury was significantly higher in the colistin group. By using PSW, no statistically significant differences emerged for mortality or clinical and microbiological cure between the two groups. No independent predictors were detected for hospital mortality or clinical cure, while for the length of stay, the only selected predictor was age, with a non-linear effect (p-value 0.025 for non-linearity) on the prolongation of hospital stay of 0.25 days (95% CI 0.10–0.39) at increasing ages (calculated over the IQR). Conclusions. Cefiderocol treatment did not differ in terms of main outcomes and safety profile from colistin-based regimens. More prospective studies with a larger number of patients are required to confirm our results.

To overcome the problems stemming from antimicrobial resistance, there have been several attempts to develop new antimicrobials in recent years. Of the highly potent drugs targeting resistant Gram-positive bacteria, daptomycin has a number of attractive characteristics that suggest its possible use in the treatment of serious infections due to these organisms. Although several pharmacokinetic and clinical studies in adults have provided data to determine how this drug should be prescribed to obtain the maximal clinical efficacy without significant risks of severe adverse events, we have not yet solved all of the problems related to the use of this antibiotic in paediatric patients. In this paper, the resolved and lingering problems of daptomycin treatment in newborns and children are reviewed and discussed. Studies have indicated that daptomycin is a promising therapeutic option for the treatment of paediatric diseases caused by MDR Gram-positive bacilli. However, before daptomycin can be licensed for use in newborns and children, further studies are needed to establish the appropriate dosages for paediatric patients of different ages. The data collected in adults can only be transferred to children older than 12 years, and the information available is not sufficient to determine the dosage that will assure the highest antimicrobial efficacy with only marginal risks of adverse events in younger patients. Thus, studies in neonates and younger infants are urgently needed to permit the use of daptomycin in the first months of life, a period in which infections due to MDR Gram-positive pathogens are increasing.