Pharmacokinetics and pharmacodynamics of oral beta-lactam antibiotics as a two-dimensional approach to their efficacy.

Pharmacokinetic and pharmacodynamic parameters are increasingly recognized as important determinants of the therapeutic efficacy of an antibiotic. For beta-lactam antibiotics, the most important determinant of the antimicrobial efficacy, and hence predictor of therapeutic efficacy, is the length of time that serum concentrations exceed the MIC. Dosing schedules for beta-lactam antibiotics should maintain serum concentrations above the MIC for the bacterial pathogen for at least 50% of the dosing interval to achieve therapeutic efficacy and prevent the development of resistance. This is a basic criterion for the clinical efficacy of beta-lactams. A combination of microbiological activity and pharmacokinetic characteristics was applied to calculate the time that serum antibiotic concentrations exceed the MIC for the major respiratory tract pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Klebsiella pneumoniae. In contrast with some other oral beta-lactam antibiotics, cefpodoxime 200 mg bd maintains serum concentrations above the MIC for each organism for at least 50% of the dosing interval and may therefore be an attractive choice for empirical therapy of community-acquired lower respiratory tract infections

Comprehension of antibiotic instructions in an outpatient Malaysian practice.

Patients may not comply with antibiotic instructions because they do not understand them. The aim of this study was to assess outpatients' ability to comprehend their antibiotic prescription labels. Two hundred and five subjects on oral antibiotic regimens from an outpatient clinic and pharmacy of a district hospital were selected in this survey. All patients were interviewed by trained clinical pharmacy students. They were asked to read the labels and then how they would take their antibiotics. The results show that 119 (58.1%) patients could interpret the label. Forty-nine (23.9%) patients knew the name of antibiotics and interpreted the directions of use correctly. One hundred sixteen (56.6%) subjects were able to recall the auxiliary information. However, only 44 (21.4%) patients were able to comprehend complete antibiotic instruction. This study demonstrates that a significant proportion of patients could not interpret the labeling instruction. The comprehension level of patients was low and significantly associated (P < 0.05) with the ability of patient to read the label contents. These observations illustrate the need for physicians and pharmacists to provide antibiotic instructions and review these instructions with the patient

In vivo study of hot compressing molded 50:50 poly (DL-lactide-co-glycolide) antibiotic beads in rabbits.

The authors investigated poly (DL-lactide-co-glycolide) beads as an antibiotic delivery system in vivo for the treatment of various surgical infections. In this study, the copolymer 50:50 poly (DL-lactide):co-glycolide was mixed with vancomycin powder and hot compressing molded at 55 degrees C to form 8 mm in diameter biodegradable antibiotic beads. The antibiotic beads were implanted in the distal femoral cavities of rabbits for in vivo investigation. The local concentration of vancomycin was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial killing and resistance to the antibiotic) for 56 days. The release was most marked during the first day. The diameters of the sample inhibition zone ranged from 8 to 18 mm, and the relative activity of vancomycin ranged from 9.1% to 100%. Only low systemic blood levels of vancomycin were measured after beads implantation. There was no increase in the concentration of blood urea nitrogen and serum creatinine after the implantation. Histological observations showed that the bead materials were biodegradable, resorbed slowly, and did not cause a significant host reaction. This study offers a biodegradable delivery system of antibiotics to treat various surgical infections

Invasive Gram-negative bacilli are frequently resistant to standard antibiotics for children admitted to hospital in Kilifi, Kenya.

OBJECTIVES: To determine the pattern of resistance among Gram-negative bacilli causing invasive bacterial disease for the antibiotics that are already in common use in Kilifi, Kenya and for two potential alternatives, ciprofloxacin and cefotaxime. Also, to determine whether prevalence and severity of resistance was increasing over time, to identify patients who are particularly at risk of resistant infections, and to explore which factors are associated with the development of resistance in our setting. METHODS: We used Etest to study antibiotic susceptibility patterns of 90 Gram-negative bacilli cultured in blood or CSF from paediatric inpatients over 8 years. RESULTS: Susceptibility to amoxicillin 28%, cefotaxime 95% and ciprofloxacin 99% did not vary significantly with age. Susceptibilities for isolates from children aged less than 14 days were: chloramphenicol, 81%; trimethoprim/sulfamethoxazole, 71%; and gentamicin, 91%. From older children, susceptibilities were: chloramphenicol, 62%; trimethoprim/sulfamethoxazole, 39%; and gentamicin, 73%. Chloramphenicol susceptibility was significantly more common among non-typhi salmonellae than other species (79% versus 53%, P<0.0005). The combination of gentamicin and chloramphenicol covered 91% of all isolates. The prevalence of resistance did not increase over time and was not more common in patients with HIV or malnutrition. Age was the only clinical feature that predicted resistance. CONCLUSIONS: Gentamicin or chloramphenicol alone was suboptimal therapy for Gram-negative sepsis, although in this retrospective study, there was no association between resistance and mortality

The purpose of our study was to determine the extent to which patients use antibiotics without consulting a physician and to examine patient characteristics associated with such oral antibiotic misuse. The study design was a prospective survey. The setting was a suburban, community, emergency department (ED). The participants were a convenience sample of oriented, ED patients who were enrolled during an 8-week period. Subjects provided written answers to standardized questions regarding their use of oral antibiotics over the 12 months preceding their ED visit. Categorical and continuous data were analyzed by chi-square and t-tests respectively. All test were 2-tailed with alpha set at 0.05. One thousand three hundred sixty three subjects were enrolled; 80% were White, 54% were female, 58% had attended college, 85% had a private physician, and 88% had health insurance. The mean age was 45 +/- 19 years. 43% of patients had used oral antibiotics within the past year. Twenty-two percent of patients indicated that their physicians routinely prescribed antibiotics for their cold symptoms. Seventeen percent of patients had taken "left-over" antibiotics without consulting their physician, most commonly for a cough (11%) or sore throat (42%), and much less frequently for urinary tract infection symptoms (0.7%). Women (19% versus 15% men; P =.04) and patients who attended college (19% versus 14% no college; P =.01) were more likely to have taken "left-over" antibiotics. A significant percentage of our ED patients had taken oral antibiotics without consulting a physician for symptoms frequently caused by viruses. Further study is warranted to examine whether local patterns of outpatient self-prescribing affect community oral antibiotic resistance

Effect of different grades of agar-agar on the nature of the test microbe growth inhibition zones in controlling antibiotic activity by means of agar diffusion

The effect of various agar grades on the size and margin character of the inhibition growth zones in assay of antibiotic activity by the agar diffusion method was studied. It was shown that not all the agar grades could be used in antibiotic activity assay. Depending on the agar type the size of the inhibition growth zones produced by the same antibiotic concentration significantly varied. The variations in the size of the inhibition growth zones depended on the agar ability to bind antibiotics and were mainly defined by the agar purity. The agars with low content of nitrogen admixtures bound the antibiotics to a low extent. The commerical grades of the agars of the South-Sea and Korsakov Plants, the experimental grade of the TINRO agar with additional purification, as well as the agars imported from Argentina and France proved to be most useful for determination of the antibiotic activity by the agar diffusion method

Binding of vancomycin group antibiotics to D-alanine and D-lactate presenting self-assembled monolayers.

Peptides terminating in -Lys-D-Ala-D-Ala, -Lys-D-Ala-L-Ala and -Lys-D-Ala-D-Lactate were covalently coupled via an N-terminal aminohexanoic acid linker to a self-assembled monolayer of HS(CH2)15CO2H on a thin gold film. Binding of the glycopeptide antibiotics vancomycin and chloroeremomycin to these surfaces was then measured using a surface plasmon resonance biosensor. Both antibiotics bound with micromolar affinity to the D-Ala-terminating surface and with millimolar affinity to the D-Lactate-terminating surface. Increasing density of these covalently attached peptides on the surface had no effect on the resultant affinities of either antibiotic for the surface. In contrast, when the lipid-anchored peptide N-alpha-docosanoyl-epsilon-acetyl-Lys-D-Ala-D-Ala was inserted into a supported lipid monolayer, the affinity of the strongly dimerizing antibiotic chloroeremomycin for the surface showed a dependence on ligand density. This was not the case with the weakly dimerizing antibiotic vancomycin. The lipid monolayer surface, which is a more realistic model of the surface of a bacterium, was thus better suited for the study of the cooperative binding interactions that occur between dimeric glycopeptide antibiotics and surface-bound ligands

Department of pharmacy-initiated program for streamlining empirical antibiotic therapy.

The outcome of a department of pharmacy-initiated "streamlining" study designed to promote cost-conscious modifications of empirically selected antibiotic therapy is described. Two hundred forty-one evaluable adult patients started on restricted-use antibiotics at this university-affiliated community private teaching hospital were enrolled in a 9-week prospective streamlining study. Patients were alternately assigned to a Control (i.e., no pharmacist-initiated streamlining recommendations offered based on culture and susceptibility reports) or a Pharmacist Intervention group (i.e., pharmacist offers recommendations to streamline therapy). A statistically significant greater number of patients had their empiric antibiotic treatment courses modified to more appropriate antibiotic choices after receipt of culture and susceptibility reports among private prescribers in the Pharmacist Intervention group (83%) than in the Control group (38%) (p = .006). Additionally, pharmacists were overall successful in gaining prescriber acceptance for 64% of recommended changes of empiric antibiotic treatment courses before the receipt of culture and susceptibility reports (e.g., dose and/or frequency changes). There was no program effect observed with respect to improved physician response to microbiologic data that would allow streamlining empirical antibiotic choices in the Housestaff (i.e., medical or surgical residents), or infectious disease consultant prescriber groups. Projected overall annual cost savings that would be achieved as a result of continued efforts by pharmacists directed at streamlining empirical "restricted" antibiotic regimens is approximately +40,000

Antibiotic combinations with redundant antimicrobial spectra: clinical epidemiology and pilot intervention of computer-assisted surveillance.

Redundant antibiotic combinations are a potentially remediable source of antibiotic overuse. At a public teaching hospital, we determined the incidence, cost, and indications for such combinations and measured the effects of a pharmacist-based intervention. Of 1189 inpatients receiving >or=2 antibiotics, computer-assisted screening identified 192 patients (16.1%) receiving potentially redundant combinations. Chart reviews showed that 137 episodes (71%) were inappropriate. Physician overprescribing errors were found in 77 episodes (56%); most involved redundant coverage for gram-positive or anaerobic organisms. In 76 episodes (55%), lapses in the medication ordering and distribution system led to the persistence in the pharmacy records of regimens no longer active according to the patient charts. The incidence of redundant antibiotic combinations was significantly higher in the intensive care unit and surgery services, compared with medical services. Interventions to discontinue redundant agents were successful in 134 (98%) of the 137 episodes. Potential drug cost savings and reduction in redundant antibiotic combination days were 10,800 dollars and 584 days, respectively; pharmacist time for patient review and intervention cost 2880 dollars. Use of redundant antibiotic combinations was common, and a pharmacist-based intervention was feasible, with a potential annualized cost savings of 48,000 dollars

What are the non-biomedical reasons which make family doctors over-prescribe antibiotics for upper respiratory tract infection in a mixed private/public Asian setting?

OBJECTIVES: To examine the non-biomedical reasons which make family doctors over-prescribe antibiotics for upper respiratory tract infection (URTI) in a mixed private/public Asian setting. METHODS: The questionnaire was sent to the members of the Hong Kong College of Family Physicians between August and December 2001. RESULTS: A total of 801 family doctors completed a postal questionnaire with an overall response rate of 65.0. A significant number of respondents (21.8) felt they might be prescribing antibiotics too often for URTI but the majority of them felt they were using antibiotics just a bit too often. Doctors who were older, more senior or in private practice were more likely to feel that they might be prescribing antibiotics too often. More than 50 of respondents thought that to satisfy the patient or his/her carer and fear of medicolegal problem if the patient deteriorates would make them very likely or likely to over-prescribe antibiotics for patients with URTIs. Public doctors might over-prescribe in order to save time, whereas private doctors might do so in order to keep patients in their practice. CONCLUSION: The results showed that doctors with certain characteristics are more likely to over-prescribe antibiotics. Factors, other than biomedical ones, may play important roles in doctor's prescription of antibiotics for URTI