Viktorija Erdeljić

The incidence of potential drug–drug interactions in elderly patients with arterial hypertension

Objective To assess the incidence and type of potential, clinically significant drug–drug interactions in elderly outpatients with arterial hypertension. Setting Three community pharmacies in Croatia. Method Eligible patients were aged 65 or older, treated for arterial hypertension and received 2 or more drugs. Potential interactions were identified by Lexi-Interact software. The software categorized each potential interaction according to clinical significance in five groups: (A) No known interaction; (B) Specified agents may interact, but there is little to no evidence of clinical concern; (C) Specified agents may interact in a clinically significant manner. Monitoring therapy is suggested; (D) The two medications may interact in a clinically significant manner. Modification of therapy is suggested; (X) Contraindicated combination. Interactions of level C, D and X were considered clinically significant. Main outcome measure The incidence and type of potential drug–drug interactions. Results There were 265 patients included in the study. Potential, clinically significant drug interactions were identified in 240 (90.6%) patients, out of which 97.9% had interactions with clinical significance C, 20.4% D, and 0.8% X. The median number of drug interactions per patient was 4. We identified 215 drug combinations with the potential to cause clinically significant interaction, out of which 83.3% had clinical significance C, 16.3% clinical significance D, and 0.4% clinical significance X. Conclusion Drug–drug interactions are common in elderly hypertensive patients. Computer-based screening could help pharmacists and physicians to recognize potential, clinically significant interactions.

Clinical pharmacology consultation: a better answer to safety issues of drug therapy during pregnancy?

PurposeDrug safety classifications give a very basic estimation of risk and should only be used as general guideline when assessing risk of pregnancy-related drug exposure or planning treatment. We conducted a study to assess the strength of association between both the clinical pharmacologists’ risk assessment and the FDA risk categorization, and adverse pregnancy outcomes.MethodsWe retrospectively reviewed records of 1,076 patients consecutively referred to the clinical pharmacology outpatient clinic for pregnancy-related drug exposure (2000–2008). Clinical pharmacologists’ risk assessments were reviewed in relation to FDA drug categorization and available pregnancy outcomes.ResultsOverall, clinical pharmacologists’ risk estimation was in agreement with the FDA risk categorization system in only 28% of consulted women, and in only 9% of women with high-risk exposure (FDA DX). Clinical pharmacologists’ risk assessment confirming high-risk drug exposure had a better positive predictive value for adverse pregnancy outcomes than the FDA DX categorization (25% vs 14% respectively), while the negative predictive values were similar (92% vs 94% respectively). Clinical pharmacologists’ risk assessment was a better predictor of adverse pregnancy outcomes compared with FDA risk categorization (OR 2.11 [95%CI 1.5-3.1; p < 0.001] vs OR 1.52 [95%CI 1.1-2.1; p = 0.014] respectively).ConclusionsAdditional evaluation beyond the FDA drug classification is essential for safer and more rational drug use in pregnancy. Clinical pharmacologists who have undergone rigorous medical training are ideally placed to consult on administration of medicines in pregnant women, thus making the prescribing of treatments in that patient category substantially safer and more rational.

Distributed lags time series analysis versus linear correlation analysis (Pearson's r) in identifying the relationship between antipseudomonal antibiotic consumption and the susceptibility of Pseudomonas aeruginosa isolates in a single Intensive Care Unit of a tertiary hospital

The relationship between antibiotic consumption and selection of resistant strains has been studied mainly by employing conventional statistical methods. A time delay in effect must be anticipated and this has rarely been taken into account in previous studies. Therefore, distributed lags time series analysis and simple linear correlation were compared in their ability to evaluate this relationship. Data on monthly antibiotic consumption for ciprofloxacin, piperacillin/tazobactam, carbapenems and cefepime as well as Pseudomonas aeruginosa susceptibility were retrospectively collected for the period April 2006 to July 2007. Using distributed lags analysis, a significant temporal relationship was identified between ciprofloxacin, meropenem and cefepime consumption and the resistance rates of P. aeruginosa isolates to these antibiotics. This effect was lagged for ciprofloxacin and cefepime [1 month (R=0.827, P=0.039) and 2 months (R=0.962, P=0.001), respectively] and was simultaneous for meropenem (lag 0, R=0.876, P=0.002). Furthermore, a significant concomitant effect of meropenem consumption on the appearance of multidrug-resistant P. aeruginosa strains (resistant to three or more representatives of classes of antibiotics) was identified (lag 0, R=0.992, P<0.001). This effect was not delayed and it was therefore identified both by distributed lags analysis and the Pearsons correlation coefficient. Correlation coefficient analysis was not able to identify relationships between antibiotic consumption and bacterial resistance when the effect was delayed. These results indicate that the use of diverse statistical methods can yield significantly different results, thus leading to the introduction of possibly inappropriate infection control measures.

Inadequate Use of Preventive Strategies in Patients Receiving NSAIDs

AbstractObjective: Little is known about the factors that influence the decision to use NSAIDs in combination with gastroprotective drugs. The aims of this observational study were to evaluate the extent to which NSAID users are prescribed concomitant gastroprotective drug regimens (‘preventive strategies’), and to determine how patient risk factors for NSAID-associated gastrointestinal toxicity and physician prescribing preferences influenced the decision to prescribe a gastroprotective drug in combination with an NSAID. Design and patients: The study was conducted on 29 June 2004 and comprised 109 eligible adult patients hospitalised at the Clinical Hospital Center, Zagreb. Use of NSAIDs and gastroprotective drugs, risk factors for NSAID-associated gastrointestinal toxicity, and physician prescribing preferences were monitored throughout the study. Results: Sixty-six percent of patients receiving proton pump inhibitors or histamine H2-receptor antagonists with NSAIDs had no risk factors for gastrointestinal toxicity. Furthermore, 29% of patients who used NSAIDs had risk factors for gastrointestinal toxicity but were not receiving gastroprotective drugs. Even though patients at risk of NSAID-associated gastrointestinal complications had higher odds of receiving preventive strategies (odds ratio 1.25), the absolute rate of utilisation of these therapies in at-risk populations was unacceptably low (69%). However, the strongest independent correlation for gastroprotective drug use was the prescribing physician, with an odds ratio of 6.40. Conclusion: This study demonstrates that an individual physician’s prescribing style largely determines the odds of receiving preventive strategies with NSAID treatment and is more important than the patient’s risk factors for gastrointestinal toxicity.

IS REFERRING PATIENTS WITH A POSITIVE HISTORY OF ALLERGIC DRUG REACTIONS OR ATOPY FOR ALLERGY TESTING TO LOCAL ANESTHETICS JUSTIFIED

Although no more than 1% of adverse reactions to local anesthetics (LA) are thought to be immunologically mediated, many patients continue to be referred to allergy clinics for allergy workup. We evaluated the impact of a history of drug hypersensitivity or atopy on results of allergy testing to LA, with the aim of determining the appropriateness of allergy testing to LA in such patients. We retrospectively analyzed medical records of 112 consecutive patients referred for allergy testing to LA in a 9-year period (1996-2005). Intradermal tests with diluted (1:10) LA were performed to identify patients at risk for immunoglobulin E (IgE)-mediated hypersensitivity reaction. The odds for being testpositive were calculated with regard to the defined risk factors (atopy, history of adverse reactions to LA or other drugs, underlying autoimmune disease). Eleven of 112 patients (9.8%) tested positive for allergy to LA. Atopy, history of adverse reactions to LA or other drugs and underlying autoimmune disease did not increase the odds for being test-positive. The prevalence of multiple drug hypersensitivity, IgE values and eosinophil count were not significantly higher among the patients who tested positive as compared to the patients who tested negative. According to our data, allergy testing to LA is not justified in patients with atopy or histories of adverse drug reactions other than to LA. Further studies using validated methods of allergy testing to LA coupled with analysis of defined risk factors are needed to definitively establish the indications for referral of patients for allergy testing to LA.

Avoiding concomitant prescription of drugs with a potential for interaction: mission impossible?

OBJECTIVE The increased prevalence of multi-drug therapy increases the risk of drug interactions. We conducted a study with the aim of evaluating the prevalence of prescribing potentially interacting drug combinations, their severity, mechanism, and in particular, their clinical relevance, in medical inpatients at two Croatian university hospitals. METHODS A cross-sectional study was conducted that included all medical inpatients receiving >= 2 drugs. Data were analyzed for 200 predefined drug-drug combinations compiled from the Micromedex data-base and literature. Two rating scales were used, one indicating the severity of a potential drug-drug interaction (pDDI) (minor, moderate, major), and the other assessing its clinical relevance (1: contraindicated; 2: avoidable; 3: consider risk-benefit ratio; 4: hardly avoidable). RESULTS The prescribing patterns were similar between evaluated hospitals. The prevalence of pDDIs was 46%. The mean number of drugs prescribed per patient was 6.2 (± 95% CI 5.9 - 6.5). Out of 200 predefined pDDIs, 96 were found in our study population with mean 2.8 pDDIs per patient (± 95% CI 2.4 - 3.1). Out of 478 single identified pDDIs, most were of moderate and major severity (56% and 33%, respectively). However, only 9% out of them were considered completely avoidable, 57% were considered hardly avoidable, and for 35% the consideration of risk-benefit ratio was recommended. Most pDDIs were classified as pharmacodynamic by mechanism of interaction (45%). Age and number of prescribed drugs were significant risk factors for prescription of potentially interacting drug combinations (OR 1.01 (± 95% CI 1.001 - 1.03) and OR 1.46 (± 95% CI 1.33 - 1.59), respectively). CONCLUSIONS Despite the high prevalence of pDDIs, only 1 in 10 was considered avoidable.

Activity of fosfomycin against nosocomial multiresistant bacterial pathogens from Croatia: a multicentric study

Aim To determine in vitro susceptibility of multiresistant bacterial isolates to fosfomycin. Methods In this prospective in vitro study (local non-random sample, level of evidence 3), 288 consecutively collected multiresistant bacterial isolates from seven medical centers in Croatia were tested from February 2014 until October 2016 for susceptibility to fosfomycin and other antibiotics according to Clinical and Laboratory Standards Institute methodology. Susceptibility to fosfomycin was determined by agar dilution method, while disc diffusion were performed for in vitro testing of other antibiotics. Polymerase chain reaction and sequencing was performed for the majority of extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) and carbapenem-resistant isolates. Results The majority of 288 multiresistant bacterial isolates (82.6%) were susceptible to fosfomycin. The 236 multiresistant Gram-negative isolates showed excellent susceptibility to fosfomycin. Susceptibility rates were as follows: Escherichia coli ESBL 97%, K. pneumoniae ESBL 80%, Enterobacter species 85.7%, Citrobacter freundii 100%, Proteus mirabilis 93%, and Pseudomonas aeruginosa 60%. Of the 52 multiresistant Gram-positive isolates, methicillin-resistant Staphylococcus aureus showed excellent susceptibility to fosfomycin (94.4%) and vancomycin-resistant enterococcus showed low susceptibility to fosfomycin (31%). Polymerase chain reaction analysis of 36/50 ESBL-producing K. pneumoniae isolates showed that majority of isolates had CTX-M-15 beta lactamase (27/36) preceded by ISEcp insertion sequence. All carbapenem-resistant Enterobacter and Citrobacter isolates had blaVIM-1 metallo-beta-lactamase gene. Conclusion With the best in vitro activity among the tested antibiotics, fosfomycin could be an effective treatment option for infections caused by multiresistant Gram-negative and Gram-positive bacterial strains in the hospital setting.