Biodegradable alginate antibiotic beads.

The authors investigated the poly-L-lysine-coated alginate beads as an antibiotic delivery system for the treatment of various surgical infections. The sodium alginate was mixed with vancomycin, coated with poly-L-lysine, and lyophilized to form five types of the biodegradable antibiotic beads. Type I, 2.5% alginate, nonpoly-L-lysine coated and nonlyophilized; Type II, 2.5% alginate, poly-L-lysine coated but nonlyophilized; Type III, 2.5% alginate, poly-L-lysine coated and lyophilized; Type IV, 5% alginate, poly-L-lysine coated and lyophilized; and Type V, 7.5% alginate, poly-L-lysine coated and lyophilized. Cytotoxicity of the alginate beads to fibroblasts and HeLa cells was evaluated by the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] colorimetric assay. A study of in vitro elution of vancomycin of the alginate antibiotic beads was performed. The results suggested that the alginate antibiotic beads present no obvious toxic risk to their use as a drug delivery system. The concentration of vancomycin in these five types of beads was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial killing and resistance to the antibiotic) for 9,11,12, 14, and 17 days respectively. The release was most marked during the first 3 days. The duration of antibiotic release was prolonged by using techniques of poly-L-lysine coating, lyophilization, and by increasing the content of alginate. This study offers a biodegradable delivery system of antibiotics to treat various surgical infections

Management of endocarditis: outpatient parenteral antibiotic treatment in Argentina.

Patients with infective endocarditis often face lengthy hospitalization for parenteral antibiotic therapy. Efforts to reduce medical costs have led to consideration of outpatient parenteral antibiotic treatment (OPAT) for these patients. However, concerns about outpatient management of complications, particularly congestive heart failure and emboli, exist. In Argentina, carefully selected patients with infective endocarditis, representing a low-risk population, have been successfully treated with OPAT. A retrospective analysis was conducted of 48 such patients. Three delivery models were used: at home with medications given by the visiting nurse, at infusion center, or at home with medications self-administered. Ten patients received OPAT only; 38 were initially hospitalized, then transferred to an OPAT program. Twenty-nine patients had streptococcal disease, 37 out of 48 patients were treated with ceftriaxone. Clinical and microbiologic cure was achieved in all patients. Three patients developed heart failure, 2 prior to starting antibiotic therapy. Four developed emboli, all prior to starting antibiotics. Surgery was required in 5 patients: 2 were treated with OPAT postoperatively and 3 had surgery after antibiotic therapy was completed. OPAT for infective endocarditis is safe in well selected patients

Serological tests for detection of fungal infection connected with prolonged antibiotic treatment after valve replacement

In recent years substantial progress has been seen in the development of approaches and methods for serological diagnosis of the mycosis. The aim of our study was to assess the clinical usefulness of serological tests for fungal infection in pts who underwent prolonged antibiotic therapy after valve replacement. MATERIAL AND METHODS: The group consisted of 27 pts after valve replacement with prolonged antibiotic therapy (6-12 weeks) due to infective endocarditis (22 pts) or sternal infection (5 pts). The samples of blood were taken 10 days after antibiotics were started and next every 10 days. Serological techniques for the diagnosis of Candidiasis consisted of antibody detection to: the cell wall polysaccharide antigen (test A), cytoplasmic protein antigen (test B) and the germ tube antigens (test C). RESULTS: Patients were divided in 3 groups due to the kinetics of the antibody responses to the Candida antigen: 1. pts with normal level of antibody during antibiotic treatment--they didn't required antifungal therapy, 2. pts with increasing level of antibody needed antifungal treatment, 3. pts with increasing kinetics of antibody responses during antibiotic and antifungal treatment needed the change of antifungal therapy, 4. Control group (pts before cardiac surgery without any sign of fungal infection). Antibody to the cytoplasmic antigen was detected infrequently. The presence of antibody to the cytoplasmic antigen was correlated with the patient clinical outcome and prognosis and necessity for change of antifungal therapy. One pt died after valve replacement due to valve dysfunction because of fungal endocarditis. CONCLUSIONS: Serological tests for Candidiasis can be a useful marker of fungal infection, prognosis and treatment in pts required prolonged antibiotic therapy after valve replacement.

Antibiotic prescribing for cystitis: how well does it match published guidelines?

PURPOSE: Cystitis is one of the most common bacterial infections seen by physicians in outpatient settings. Published clinical guidelines by the Infectious Disease Society of America and other organizations have been established to enable effective treatment, while attempting to decrease cost and limit antibiotic resistance. METHODS: Insurance claims data for employees and dependents of a single Midwest corporation, with Preferred Provider Organization coverage, diagnosed with cystitis between 1996 and 1999 were matched to prescription drug claims for those who filled an antibiotic prescription within 3 days of diagnosis. RESULTS: For acute and recurrent cystitis physicians prescribed trimethoprim-sulfamethoxazole 37% and 18% respectively. The other most common antibiotics prescribed were the broad-spectrum flouroquinolones, and nitrofurantoin. The mean duration for these prescriptions was 10 days regardless of whether the infection was acute or recurrent. CONCLUSIONS: The first line recommended antibiotic, trimethoprim-sulfamethoxazole, was prescribed in 37% of acute infections, and for considerably longer than the suggested 3-day course of therapy. Steps should be taken to educate physicians and patients on the choice and dosage of antibiotics for cystitis to minimize emergence of antibiotic resistance

Cloning, overexpression, and purification of aminoglycoside antibiotic 3-acetyltransferase-IIIb: conformational studies with bound substrates.

Aminoglycoside 3-acetyltransferase-IIIb (AAC3), which acetylates N3 amine of aminoglycoside antibiotics, was cloned from P. Aeruginosa and purified from overexpressing E. coli BL21 (DE3) cells. Bound conformations of kanamycin A and ribostamycin, in the active site of the enzyme that modifies the essential N3B of aminoglycoside antibiotics, were determined by NMR spectroscopy. Experimentally determined interproton distances were used in a simulated annealing protocol to determine enzyme-bound conformations of both antibiotics. Two conformations, consistent with the NOE restraints, were determined for ribostamycin. The only difference between the two conformers was the orientation of the A ring with respect to the rest of the molecule. The average glycosidic dihedral angles were Phi(1A) = -22 degrees +/- 3 and Psi(1A) = -42 degrees +/- 1 (conformer 1) and Phi(1A) = -67 degrees +/- 0.7 and Phi(1A) = -59 degrees +/- 0.8 (conformer 2). Three conformers were determined for the enzyme-bound kanamycin A. Two conformers of kanamycin A were matched well with the two conformers of ribostamycin when the A and the B rings of the antibiotics were superimposed. Conformations of kanamycin A and ribostamycin were compared to those of other aminoglycosides that are bound to different enzymes and RNA. The results lend further support to our earlier hypothesis that the A and B rings of aminoglycosides adopt a conformation that is recognized not only by the aminoglycoside-modifying enzymes but also by RNA (Serpersu, E. H., Cox, J. R., Digiammarino, E. L., Mohler, M. L., Akal, A., Ekman, D. R., and Owston, M. (2000) Cell Biochem. Biophys. 33, 309-321). These results may be useful in designing new antibiotics to combat the antibiotic resistance against infectious diseases

Prevention of antibiotic resistance needs informed parents

Antibiotic resistance is becoming worldwide a major challenge. Increasing rate of multidrug resistant bacteria is directly linked with the consumption of antibiotic. Children are the greatest consumers of antibiotics, but this large pediatric prescription is not justified, and responds, at least in part, to a "parental pressure". Therefore information to the parents about antibiotic is recommended. In order to promote this information the American Academy of Pediatrics recently wrote a booklet entitled "Your child and antibiotics" which is presented

Genetic determinants of microbial resistance to antibiotics.

Emergence of antibiotic resistance is related to the ease of mutation, to the extent of exchange of genetic information in bacteria by conjugation, transformation, and transduction, and to the large-scale use of antimicrobial agents in the biosphere. In addition to the development of resistance through chromosomal mutation and exchange of chromosomal genes among organisms, there is a more profound enlargement of the gene pool by the dissemination and amplification of plasmids. Two examples of the exchange of antibiotic resistance are analyzed: the transfer of plasmids from Bacteroides fragilis to Escherichia coli and the emergence of antibiotic-resistant strains of STreptococcus pneumoniae. Plasmids encoding antibiotic resistance in B. fragilis were transferred to E. coli by DNA-mediated transformation and conjugation. The beta-lactamase in the transformants and transconjugants displayed the same substrate specificity and electrophoretic mobility as the donor strain. The plasmid apparently was integrated rapidly into the chromosome of the recipient strain. Multiple antibiotic-resistant strains of S. pneumoniae were analyzed for plasmids, and none were detected. Furthermore, no evidence of linkage between the traits of multiple antibiotic resistance was observed. beta-Lactamase was not detected in the penicillin-resistant strains; therefore, it is likely that the resistance in these strains was chromosomal rather than plasmid-mediated. The range of genetic exchange and the use of Koch's postulates in determining the genetic mechanism of antibiotic resistance are illustrated and discussed

Restriction of third generation cephalosporin use reduces the incidence of Clostridium difficile-associated diarrhoea in hospitalised patients.

Third generation cephalosporin antibiotics (3GC) have become the antibiotics of choice in many hospitals in recent years for the treatment of infections such as community-acquired pneumonia. However, increased use of 3GCs has also been associated with a rise in the occurrence of antibiotic-associated diarrhoea due to Clostridium difficile, as well as an increase in the prevalence of antibiotic resistant organisms such as methicillin resistant Staphylococcus aureus, vancomycin resistant entrococci, and extended-spectrum beta-lactamase-producing gram negative bacilli. In Western Australia, greater use of 3GCs was shown to correlate with more Clostridium difficile-associated diarrhoea (CDAD) in a large acute care teaching hospital during the 1980s. During the 1990s, the use of 3GCs in this hospital remained high and, at the end of 1998, a policy was introduced to prevent the use of ceftriaxone (the only 3GC in use) without prior approval. This resulted in a decline in 3GC use and a 50 per cent reduction in the incidence of CDAD during 1999 and 2000. To strengthen these observations, the impact of the 3GC policy on the occurrence of CDAD was analysed using time-series intervention analysis that showed a statistically significant decrease in the occurrence of CDAD during the post-intervention period after controlling for exogenous factors. Thus, changes in antibiotic prescribing practices can influence the incidence of CDAD and, potentially, antibiotic resistant pathogens

Importance of professional proposals in the era of broadening antibiotic resistance

A great degree of neglection has been portrayed on the consideration in two most important professional proposals in 6906 patients of 44 praxis in the basic health care in 1996: 1. the obviously viral respiratory diseases (including acute bronchitis, ordinarily) was treated in 56% of cases with antibacterial drugs (in 83% of all treatments with broad spectrum antibiotics), and 2. for patients with Streptococcal infections too broadened spectrum antibiotics for this purpose were undesirably prescribed (in 75.5% of treatments) by physicians. Taking into consideration the suitable efficient ("evidence based") anticausal therapy and professional proposals, as well, in 63.6% of all antibiotic therapy could be avoided by physicians. By all means, these prescribed legion of the aimless, unnecessary and simultaneously too broadened spectrum antibacterial drugs served for the spreading of antibiotic resistance only, and all of them were the results of the neglection of the most important professional proposals. These unnecessary treatments--excluding the increase of resistance or the improper, unsubstantiated raise in hopes of patients--cost too much: the sum of expenses were 49.5% of the cost for antibiotics in Hungary in 1996 (in our estimation). To measure and examine periodically the quality level of primary infectological care, new quality indicators were appointed by the authors: the attained quality levels of each medical praxis would have to be compared and approached to the desirable level of quality indicators (reflecting the "evidence based" infections care) for the abolition of the unreasonable, expensive and dangerous practice for patients, as well. It appears, that the wide application of the appropriate, "evidence based" anticausal therapy would be reached with control of offered quality (the offered values of the quality indicators) of physicians in primary care, only. The introduction of quality assurance in basic health care needs urgent comprehensive official action.

Evaluation of antibiotic sensitivity of pathogenic vibrios of various species

The recent increase of the number of antimicrobials and isolation of antibiotic resistant strains from humans and environmental objects is indicative of the necessity of further investigation of antibiotic susceptibility of the representatives of the genus Vibrio pathogenic for man to provide rational therapy of the diseases due to them. Susceptibility of 160 strains of pathogenic vibrios of 9 species to 11 antibiotics and chemotherapeutic drugs was assayed by the method of serial dilutions in agar media. The isolates were shown to be highly susceptible to chloramphenicol, doxycycline, cefotaxime, nalidixic acid and ciprofloxacin which made it possible to consider them as the drugs of choice in the treatment of the diseases caused by the microorganisms. A tendency to form polyantibiotic resistant strains within every species of tested pathogenic vibrios was observed. It conditioned the prospects of further profound study of the phenomenon with the analysis of the genetic determination of antibiotic resistance markers in pathogenic vibrios