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Background Adverse drug events (ADEs) can be prevented by deploying clinical decision support systems (CDSS) that directly assist physicians, via computerized order entry systems, and clinical pharmacists performing medication reviews as part of medical rounds. However, physicians using CDSS are known to be exposed to the alert-fatigue phenomenon. Our study aimed to assess the performance of PharmaCheck—a CDSS to help clinical pharmacists detect high-risk situations with the potential to lead to ADEs—and its impact on clinical pharmacists’ activities. Methods Twenty clinical rules, divided into four risk classes, were set for the daily screening of high-risk situations in the electronic health records of patients admitted to our General Internal Medicine Department. Alerts to clinical pharmacists encouraged them to telephone prescribers and suggest any necessary treatment adjustments. PharmaCheck’s performance was assessed using the intervention’s positive predictive value (PPV), which characterizes the proportion of interventions for each alert triggered. PharmaCheck’s impact was assessed by considering clinical pharmacists as a filter for ruling out futile alerts and by comparing the final clinical PPV with a pharmacist (the proportion of interventions that led to a change in the medical regimen) to the final clinical PPV without a pharmacist. Results Over 132 days, 447 alerts were triggered for 383 patients, leading to 90 interventions (overall intervention PPV = 20.1%). By risk class, intervention PPVs made up 26.9% (n = 65/242) of abnormal laboratory value alerts, 3.1% (4/127) of alerts for contraindicated medications or medications to be used with caution, 28.2% (20/71) of drug–drug interaction alerts, and 14.3% (1/7) of inadequate mode of administration alerts. Clinical PPVs reached 71.0% (64/90) when pharmacists filtered alerts and 14% (64/242) if they were not doing it. Conclusion PharmaCheck enabled clinical pharmacists to improve their traditional processes and broaden their coverage by focusing on 20 high-risk situations. Alert management by pharmacists seemed to be a more effective way of preventing risky situations and alert-fatigue than a model addressing alerts to physicians exclusively. Some fine-tuning could enhance PharmaCheck's performance by considering the information quality of triggers, the variability of clinical settings, and the fact that some prescription processes are already highly secured.

Assessing bacterial viability by molecular markers might help accelerate the measurement of antibiotic-induced killing. This study investigated whether rRNA could be suitable for this purpose. Cultures of penicillin-susceptible and penicillin-tolerant (Tol1 mutant) Streptococcus gordonii were exposed to mechanistically different penicillin and levofloxacin. Bacterial survival was assessed by viable counts and compared to quantitative real-time PCR amplification of either the 16S rRNA genes or the 16S rRNA, following reverse transcription. Penicillin-susceptible S. gordonii lost ≥4 log 10 CFU/ml of viability over 48 h of penicillin treatment. In comparison, the Tol1 mutant lost ≤1 log 10 CFU/ml. Amplification of a 427-bp fragment of 16S rRNA genes yielded amplicons that increased proportionally to viable counts during bacterial growth but did not decrease during drug-induced killing. In contrast, the same 427-bp fragment amplified from 16S rRNA paralleled both bacterial growth and drug-induced killing. It also differentiated between penicillin-induced killing of the parent and the Tol1 mutant (≥4 log 10 CFU/ml and ≤1 log 10 CFU/ml, respectively) and detected killing by mechanistically unrelated levofloxacin. Since large fragments of polynucleotides might be degraded faster than smaller fragments, the experiments were repeated by amplifying a 119-bp region internal to the original 427-bp fragment. The amount of 119-bp amplicons increased proportionally to viability during growth but remained stable during drug treatment. Thus, 16S rRNA was a marker of antibiotic-induced killing, but the size of the amplified fragment was critical for differentiation between live and dead bacteria.

Methicillin-resistant Staphylococcus aureus (MRSA) have developed resistance to virtually all non-experimental antibiotics. They are intrinsically resistant to beta-lactams by virtue of newly acquired low-affinity penicillin-binding protein 2A (PBP2A). Because PBP2A can build the wall when other PBPs are blocked by beta-lactams, designing beta-lactams capable of blocking this additional target should help solve the issue. Older molecules including penicillin G, amoxicillin and ampicillin had relatively good PBP2A affinities, and successfully treated experimental endocarditis caused by MRSA, provided that the bacterial penicillinase could be inhibited. Newer anti-PBP2A beta-lactams with over 10-fold greater PBP2A affinities and low minimal inhibitory concentrations were developed, primarily in the cephem and carbapenem classes. They are also very resistant to penicillinase. Most have demonstrated anti-MRSA activity in animal models of infection, and two--the carbapenem CS-023 and the cephalosporin ceftopibrole medocaril--have proceeded to Phase II and Phase III clinical evaluation. Thus, clinically useful anti-MRSA beta-lactams are imminent.

Objective To develop and evaluate a coding system integrated into pharmaceutical software to routinely report and assess the process of community pharmacists’ interventions related to medical prescriptions. Setting A convenient sample of 20 Swiss community pharmacies. Method Pharmacists documented their interventions concerning all drug-related problems (DRPs) related to medical prescriptions during four consecutive weeks in 2005. The coding system assesses each step of the DRP management process; that is, the type of problem, possible negative outcomes, pharmaceutical decisions, and individuals involved. In order to be comprehensive, the management process of technical problems related to prescriptions and clinical DRPs was analysed separately. Main outcome measure DRP intervention rate and characterization of each step of the process. Results Of 38,663 prescriptions, 287 clinical DRPs required interventions. This corresponds to a mean intervention rate of 0.77% per pharmacy (SD = 0.61%). There was a large variability among pharmacies (0–2.6%). Most of the clinical DRPs were associated with dosage problems (n = 91) and drug–drug interactions (n = 45). The most frequent potential negative outcomes reported were quantitative inefficacy (n = 101) and quantitative safety (n = 94). Two-thirds of clinical DRPs required a prescription modification (n = 186), the most frequent being a change in dosage or drug regimen. In 110 interventions (38%), physicians were immediately contacted to take part in the decision. In 122 interventions (43%), pharmacists managed the interventions alone. However, in 55 interventions (19%), pharmacists managed the DRPs with the patient. From these 287 clinical interventions, 134 different codes were reported. Seven hundred and thirty-six technical problems related to prescriptions required intervention, which corresponded to a mean intervention rate of 1.90% per pharmacy. The main type of problem was a discrepancy with the medication record (n = 208). There were 494 instances that required a prescription modification. Pharmacists resolved 45% of all technical problems by themselves. Conclusion The developed coding system could describe the management process for DRPs. The observed intervention rate and the frequency of steps involved were comparable to those previously observed for pharmacists’ interventions. Data regarding the entire process used to manage drug-related problems can be useful in improving medication safety, education, and collaborative care.