Generic drug prescriptions following hospital discharge: a prospective study in France.

AIMS: Systematic generic prescription at discharge could reduce confusion on drug-name usage, decrease commercial influence on medicine, and reduce drug-related expenditures. This study aimed to analyze generic drug prescriptions at discharge from hospital and to estimate the potential savings associated with a total substitution policy (substitution of every substitutable drug for its cheapest generic counterpart). METHODS: Drug prescriptions before admission and at discharge of all patients from three medical units of a university hospital were prospectively collected for five weeks without informing prescribers. RESULTS: Prescriptions from 85 patients were analyzed. On admission, 68 patients (80%) received 413 drugs; 141 were substitutable brand-name drugs and 23 (16%), which were directly prescribed as generics. At discharge, 488 drugs were prescribed to the 85 patients; 180 were substitutable drugs but only 5 (2.8%) were written as generics on prescription pads, a decrease of 78% (p<0.0001) compared to admission. In average, generics were 18% less expensive than brand-name drugs. Some common therapeutic classes offered even greater price difference, such as proton-pump inhibitors (42%), statins (32%), or antihypertensive agents (28%). Potential savings from a total substitution policy at discharge were estimated to €1512 per 1000 patients per week; for lifetime drugs, savings amounted to €18,960 per 1000 patients per year. CONCLUSIONS: Very few drugs are written as generics on medical forms at discharge in France. Hospital practitioners should be encouraged to prescribe generics, particularly in chronic diseases. A broad generic prescription policy at hospital discharge would result in substantial savings for health insurance.

Phylogenetic analysis of proteolytic Acinetobacter strains based on the sequence of genes encoding aminoglycoside 6'-N-acetyltransferases.

The sequence of seven aac(6')-I genes encoding aminoglycoside 6'-N-acetyltransferases from proteolytic Acinetobacter strains including genomic species 14, 15, 16, and 17 and from ungrouped proteolytic strains 631, 640, and BM2722 was determined. Pulsed-field gel electrophoresis of genomic DNA of these strains and of Acinetobacter sp. 6 CIP A165 digested with SfiI followed by hybridization with rRNA and aac(6')-I specific probes indicated that these genes were located in the chromosome. Phylogenetic analysis of the genes indicated that aac(6')-I of A. baumannii, Acinetobacter ungrouped strain 631, and Acinetobacter sp. 16 formed a cluster (91.5 to 92.3% identity) whereas aac(6')-I of Acinetobacter sp. 15, sp. 17, and Acinetobacter ungrouped strain BM2722 formed another cluster (90.7 to 94.6% identity). A third cluster was constituted by A. haemolyticus and Acinetobacter sp. 6 (83.6% identity). The phylogeny drawn from aac(6')-I sequences was consistent with that based on DNA-DNA hybridization and phenotype comparison. The aac(6')-I genes were all species specific except for aac(6')-Ih located in a 13.7-kb non conjugative plasmid from A. baumannii BM2686. We conclude that aac(6')-I genes may be suitable for identification at the species level and for analysis of the phylogenetic relationships of Acinetobacter.

Characterization of IS18, an element capable of activating the silent aac(6')-Ij gene of Acinetobacter sp. 13 strain BM2716 by transposition.

Insertion sequence IS18 was detected by analysis of the spontaneous aminoglycoside resistant mutant Acinetobacter sp. 13 strain BM2716-1. Insertion of the element upstream from the silent acetyltransferase gene aac(6')-Ij created a hybrid promoter that putatively accounts for the expression of the aminoglycoside resistance gene. The 1, 074-bp IS18 element contained partially matched (20 out of 26 bases) terminal inverted repeats, one of which overlapped the 3' end of a 935-bp open reading frame potentially encoding a protein related to the transposases of the IS30 family. IS18 was found in 6 out of 29 strains of Acinetobacter sp. 13 but not in 10 strains each of A. baumannii and A. haemolyticus.

Study of the correlation between MEIA and ELISA methods for FK 506 determination in liver transplant recipients.

BACKGROUND AND OBJECTIVES: FK 506 is an immunosuppressive macrolide advocated for prevention of graft rejection. Plasma or blood FK 506 levels must be determined to strike a balance between FK 506 toxicity and graft rejection. The first aim of this study was to compare an automated microparticle enzyme immunosorbent assay (MEIA) method (on whole blood) with the reference enzyme-linked immunosorbent assay (ELISA) method (on plasma). A second aim was to compare the two methods for prediction of FK 506 nephrotoxicity. PATIENTS AND METHODS: Forty-seven patients were studied comprising 128 samples. All were treated with FK 506 on a compassionate basis. For each patient, the concentrations of FK 506 were determined in plasma by means of ELISA and in whole blood by MEIA. RESULTS: The repeatability and the reproducibility of these two methods were similar. The inter-patient correlation coefficient between MEIA and ELISA, determined on 128 samples from 47 liver recipients, was satisfactory (r = 0.82). From these 47 patients, the intra-patient correlation coefficients were calculated for 17 of them. The intra-patient correlation coefficients were between 0.63 and 0.98 for 15 patients, and between 0.26 and 0.55 in the remaining two cases. Mean creatinine plasma levels in the 55 samples below the median FK 506 value in the MEIA method and in the 55 with values above the median (120 and 134 mumol/litre, respectively) were significantly different (P < 0.05), as were those using the reference ELISA methods (115 and 139 mumol/litre, P < 0.01). In contrast, there was no significant difference between the mean creatinine plasma levels in the 55 samples with FK 506 levels below the median using both methods or between those above the median. CONCLUSION: The automated MEIA method, being simpler and more rapid than the ELISA method, should now be preferred for therapeutic monitoring of FK 506.

Loss of intrinsic aminoglycoside resistance in Acinetobacter haemolyticus as a result of three distinct types of alterations in the aac(6')-Ig gene, including insertion of IS17.

The distribution of the aac(6')-Ig gene, encoding aminoglycoside 6'-N-acetyltransferase-Ig [AAC(6')-Ig], was studied in 96 Acinetobacter haemolyticus strains and 12 proteolytic Acinetobacter strains, including Acinetobacter genomospecies 6, 13, and 14 and 3 unnamed species assigned to this genomic group by DNA-DNA hybridization. This gene was detected by DNA-DNA hybridization in all 96 A. haemolyticus strains and by PCR in 95 strains but was not detected in strains of other species, indicating that it may be used to identify A. haemolyticus. Three A. haemolyticus strains were susceptible to tobramycin and did not produce an aminoglycoside 6'-N-acetylating activity, although they contained aac(6')-Ig-related sequences. An analysis of three susceptible A. haemolyticus strains indicated that aminoglycoside resistance was abolished by the following three distinct mechanisms: (i) a point mutation in aac(6')-Ig that led to a Met56-->Arg substitution, which was shown by analysis of a revertant to be responsible for the loss of resistance; (ii) a polythymine insertion that altered the reading frame; and (iii) insertion of IS17, a new member of the IS903 family. These observations indicated that AAC(6')-Ig is not essential for the viability of A. haemolyticus, although the aac(6')-Ig gene was detected in all members of this species.

Characterization of the aac(6')-Ik gene of Acinetobacter sp. 6.

The aac(6')-Ik gene which confers resistance to aminoglycosides in Acinetobacter sp. 6 CIP A165 was characterized. The resistance gene was identified as a coding sequence of 438 bases pairs corresponding to a protein with a calculated mass of 16627 Da. Alignment of aac(6')-Ik with aac(6')-Ig from Acinetobacter haemolyticus indicated 83% identity. Like aac(6')-Ig of A. haemolyticus and aac(6')-Ij of Acinetobacter sp. 13, the aac(6')-Ik gene was apparently located in the chromosome and was species specific. The high degree of identity between aac(6')-Ig and -Ik, compared with genomic DNA relationships between the host species, indicated that these genes have diverged from a common ancestor in a parental Acinetobacter species.

Open trial of tacrine therapy in 70 HIV-infected patients.

The purpose of this study consisted in following-up the biological and clinical parameters in HIV infected patients treated with tacrine (THA). THA (150-300 mg/d) was administrated to 70 patients (39 IVC I and 31 IVC II and III). Thirty-five were treated after discontinuation of AZT treatment and 35 as a first intention treatment. Thirty (43%) patients showed an increase in the CD4+ cell count by more than 50% relative to pretreatment levels and fifteen (21%) showed an increase of more than 25%. p24 antigenemia (Ag p24) became negative in eight of the twenty-seven patients who were initially positive, and decreased by 25 and 50% in nine and six patients, respectively. Ag p24 was therefore decreased in 80% of the patients. From a clinical point of view, there were two deaths (3%) and five opportunistic infections (7%). The treatment with THA was stopped in five patients because of side effects (nausea, rash). Neither hepatotoxicity, hematotoxicity, nor pancreatitis was observed during the THA treatment. In group II and III only two patients (6%) developed an opportunistic infection.