Use of antibiotic-loaded polymethyl methacrylate beads in the management of musculoskeletal sepsis-a retrospective study.

OBJECTIVE. To assess the use of antibiotic-loaded polymethyl methacrylate beads in the management of chronic osteomyelitis of different aetiologies: infected osteosynthesis, infected open fractures, and haematogenous osteomyelitis. METHODS. Records of 49 patients with chronic osteomyelitis who were treated at Department of Orthopaedics, Kasturba Medical College, from 1995 to 1999 were studied retrospectively. The diagnosis of chronic osteomyelitis was made on the basis of clinical and radiographic features. Of the 49 patients, 4 had haematogenous osteomyelitis, which later proved to be tuberculosis, and were thus excluded. Antibioticloaded acrylic beads were implanted in the remaining patients after thorough debridement. The implant was removed primarily in 16 patients with infected osteosynthesis, who then underwent decompression and sequestrectomy. All wounds were closed primarily. Peri-operative antibiotics were given for 7 days. Beads were removed at the end of 3 weeks followed by bone grafting in 26 patients. Patients were followed up for an average period of 3.7 years. RESULTS. The infective organisms were sensitive to gentamycin in 26 cases and resistant in 19 cases; 14 cases were sensitive to cefuroxime, 11 to cloxacillin, 8 to ampicillin, and 5 to cotrimoxazole. Seven cases were resistant to all antibiotics tested. Of the 19 patients with gentamycin-resistant infection, only one had a poor result. No adverse systemic side-effects such as ototoxicity or nephrotoxicity were seen. Infection did not recur in 39 patients, but 6 patients had low-grade persistent infection at the last follow-up visit. CONCLUSION. In chronic infections, especially those following osteosynthesis, antibiotic beads are a valuable adjuvant. The most valuable advantage is that the wound can be closed primarily, thereby reducing the incidence of nosocomial infections and requirement of nursing care

The effect of rapid respiratory viral diagnostic testing on antibiotic use in a children's hospital.

BACKGROUND: Acute viral respiratory disease is the most common reason for pediatric hospitalization in the United States. Viral illnesses may be mistaken for bacterial infection, and antibiotic therapy may be prescribed. Overprescribing of antimicrobials for viral illness is a factor contributing to increasing antimicrobial resistance among bacterial pathogens encountered in pediatrics. OBJECTIVE: To determine if the availability of a rapid diagnostic test for respiratory viruses would affect antibiotic use in a children's hospital. DESIGN: Retrospective medical record review. SETTING: A 232-bed urban children's hospital. PARTICIPANTS: All hospitalized infants and children who underwent rapid testing (SimulFluor Respiratory Screen; Chemicon International Inc, Temecula, Calif) for respiratory viruses by direct fluorescent assay (DFA) during 2 successive winter seasons. MAIN OUTCOME MEASURES: Rates of antibiotic prescribing in DFA-positive and DFA-negative patients during the 2 study periods. RESULTS: During the first winter season, DFA-positive patients had fewer days using intravenous antibiotics (2.4 vs 4, P =.04), fewer days using oral antibiotics (0.25 vs 2.5, P =.04), and fewer discharge prescriptions for oral antibiotics (37% vs 52%, P =.02) when compared with DFA-negative patients. Intravenous antibiotics were initiated less often for DFA-positive patients during the second winter season than during the first (26% vs 44%, P =.008). CONCLUSIONS: Direct fluorescent assay testing was associated with a decrease in inappropriate antibiotic use. The availability of rapid viral diagnostics is an important tool for decreasing antibiotic prescribing in pediatric patients

Evaluation of the antibiotic effect of treatment of maxillary sinusitis.

As the effect of antibiotic treatment of maxillary sinusitis has been questioned, the elimination of bacteria from sinus secretions was studied during antibiotic treatment. Penicillin V, azidocillin, tetracycline or doxycycline was administered to 54 patients with maxillary sinusitis. Samples of sinus secretion were aspirated both before treatment and 2-3 days after the onset of treatment. When the antibiotic concentration was below the upper limit of MIC for sensitivity group 1, bacterial growth was present in practically all samples. When the antibiotic concentration equalled or was above this limit, there was no bacterial growth in about half of the samples. A prerequisite for antibiotic effect--elimination of bacteria--is that the antibiotic concentration is well above the MIC of the bacteria at the site of infection. The choice between bactericidal or bacteriostatic antibiotics appeared unimportant. Bacterial survival in the maxillary sinus despite a high antibiotic concentration in the sinus illustrates that MIC values determined in the laboratory do not always mirror the sensitivity of bacteria to antibiotics in vivo

Risk of clinical blood dyscrasia in a cohort of antibiotic users.

Blood dyscrasias, although rare, can be fatal. Many drugs, including antibiotics, are associated with these dyscrasias. We conducted a cohort study with a nested case-control analysis using data from the General Practice Research Database to estimate incidence rates of clinical blood dyscrasias in the general population and to examine their association with use of antibiotic drugs. The study population consisted of patients aged 5-69 years receiving at least one antibiotic prescription from January 1994-September 1998. The final cohort consisted of 822,048 persons who received 1,507,307 antibiotic prescriptions during the study period. The main outcome measure was a diagnosis of neutropenia, agranulocytosis, hemolytic anemia, thrombocytopenia, bicytopenia, pancytopenia, or aplastic anemia. We confirmed 122 patients who developed clinical blood dyscrasias. The incidence was 3.3/100,000 person-years in the general population. Patients older than 60 years (relative risk [RR] 2.8, 95% confidence interval [CI] 1.6-5.0) and those who took phenothiazines (RR 49.0, 95% CI 4.9-488.2) had an increased risk of blood dyscrasia. Users of antibiotics had an RR of 4.4 (95% CI 2.6-7.5), and patients taking more than one class of antibiotics had an RR of 29.1 (95% CI 9.1-92.8). Among individual antibiotic classes, the greatest risk was with cephalosporins (RR 13.8, 95% CI 3.6-52.6). Although uncommon, our study supports an association between blood dyscrasias and antibiotics

Comparative studies on in vitro activities of kasugamycin and clinically-used aminoglycoside antibiotics.

Kasugamycin, a unique aminoglycoside antibiotic, has been used for many years solely for crop protections. In general, aminoglycoside antibiotics possess broad and strong inhibitory activity against both Gram-positive and -negative bacteria, however, kasugamycin merely exhibits limited activity against phytopathogenic microbes such as Pyricularia oryzae and certain strains of pseudomonads. Recently, in human and animal chemotherapy, it has been seriously concerned about the emergence of multiply resistant bacteria by consumption of a large amount of antibiotics not only for therapy but also for growth-promotion of farm animals. It was believed that kasugamycin, the agricultural antibiotic, does not undergo any cross-resistance with other clinically important aminoglycoside antibiotics because of its weak or almost no activity against common pathogenic microbes except for some phytopathogenic fungi and pseudomonads. However, no confirmative study on this fact has been published so far. In this study, we compared activity of kasugamycin with those of twelve clinically used aminoglycoside antibiotics against susceptible standard strains and well-characterized aminoglycoside-resistant strains as well as clinically isolated strains, in order to show the least potential of kasugamycin to create cross-resistant human pathogens against clinically important aminoglycoside antibiotics

Antibiotic use in an Italian university hospital.

The aim of this retrospective observational study was to investigate: a) expenditure for antibiotics with respect to the total pharmacy drug budget and to costs of other medical devices; b) the most frequently used antimicrobial classes and molecules; c) the clinical units that most frequently use antimicrobial therapy; d) the preferred route of administration; e) consumption patterns of antibiotics over two periods (January-September 1999 and January-September 2000). The consumption of a single antimicrobial agent was expressed as daily defined doses (DDD) per 100 bed days. In 1999 drugs accounted for 56% of the total costs but decreased to 46% in 2000. Antibiotics accounted for 15% of the pharmacy's overall acquisition costs in 1999 and dropped to 13% in 2000. In both 1999 and 2000, penicillins were used most, followed by cephalosporins and aminoglycosides. In 1999, the most frequently used antibiotic was amoxicillin (4.02 DDD per 100 bed days) followed by ceftazidime, ampicillin, ceftriaxone, and co-amoxiclav. In 2000 ceftriaxone was the most commonly used antibiotic (4.35 DDD per 100 bed days) followed by co-amoxiclav, amoxicillin, ceftazidime. The general surgery, medical therapy and infectious diseases units accounted for the majority of penicillin consumption, while cephalosporins were most widely used in general surgery, orthopedics and neurosurgery units. Parenteral administration was the most widely used route in both years

In vivo application of biodegradable controlled antibiotic release systems for the treatment of implant-related osteomyelitis.

In this study the construction and in vivo testing of antibiotic-loaded polyhydroxyalkanoate rods were planned for use in the treatment of implant-related osteomyelitis. The rods were constructed of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate), carrying 50% (w/w) Sulperazone or Duocid. They were implanted in rabbit tibia in which implant-related osteomyelitis (IRO) had been induced with Staphylococcus aureus. The effectiveness of the antibiotics in the treatment of IRO was determined. The establishment of IRO with bacterial inoculation was complete after 3 weeks with 100% infection rate in all groups. There was no contamination or super-infection. Both antibiotics were found to be highly effective against the bacteria. Following the application of Sulperazone-P(3-HB-co-4-HB) rods, no infective agents could be isolated from the infection site within the 6-week test period, indicating complete treatment of the infection. Macroscopical evaluation at follow-up revealed no drainage, minimal swelling and increase in local warmth, most probably due to the surgery rather than to a reaction towards the implant. The overall scores for radiological findings by the end of 6 weeks were 0.8/5 for the antibiotic-loaded rod implanted in the right limb, and 1.1/5 for the antibiotic-free rod implanted in the left limb. There was no statistical difference between the antibiotic-loaded and antibiotic-free polymeric rods. In vivo drug release was almost complete within the first week. One interesting observation, however, was that the therapy was still very effective even when the release rate was very high. In the SEM of in vitro tested rods, the polymeric component was unchanged in 2 weeks while the drug leached out, leaving voids behind. In vivo, however, the morphology of the implant was significantly modified within 6 weeks post-implantation. Since a substantial degree of the in vivo drug release was complete within 1 week, we believe that dissolution of the drug must be the predominant mechanism through which the drug release is controlled

Optimizing antibiotic therapy-the Aberdeen experience.

OBJECTIVE: To study the quality and continuity of treatment in the Acute Medicines Assessment Unit (AMAU) with regard to empirical prescription of antibiotics, mode of administration, adherence to ward antibiotic policy, as well as collection, awareness and utilization of microbiological investigations. METHODS: A prospective study over a 3-month period at the AMAU, Aberdeen Royal Infirmary (ARI), a teaching hospital in north-eastern Scotland, was performed. The study included all patients started on empirical antibiotics on admission to the AMAU and followed up until their discharge. RESULTS: Of 1303 patients admitted, 221 (17%) were started on empirical antibiotics. This was in accordance with hospital antibiotic policy in 52% of cases. Appropriate specimens were taken from 77% of patients. Culture results showed that 29% (n = 65) of the patients had clinically significant growth of organisms. Of the 65 patients with clinically significant culture results, 49% (n = 32) were on an inappropriate empirical regimen. In 55%, the medication was not changed to a more appropriate antibiotic. In 72% of the patients with a negative culture, the culture report had no obvious effect on the duration or type of antibiotic being administered. Intravenous antibiotics were used in 60% of patients. CONCLUSION: This study demonstrates a significant overuse of antibiotics, especially intravenous forms, despite a paucity of positive sepsis parameters and chest X-ray findings in these patients The duration of treatment could be shortened and an early switch policy introduced if culture results and sepsis profiles were taken into consideration, as there was a large number of unproven infections. Suggestions are made about how these improvements in prescribing could be made within the current administrative set-up of AMAUs

Clostridium difficile: prevalence in horses and environment, and antimicrobial susceptibility.

REASONS FOR PERFORMING STUDY: Clostridium difficile has been associated with acute colitis in mature horses. OBJECTIVES: To survey C. difficile colonisation of the alimentary tract with age, occurrence of diarrhoea and history of antibiotic therapy; and to study the occurrence and survival of C. difficile in the environment and antimicrobial susceptibility of isolated strains. METHODS: A total of 777 horses of different breeds, age and sex were studied. Further, 598 soil samples and 434 indoor surface samples were examined. Antimicrobial susceptibility of 52 strains was investigated by Etest for 10 antibiotics. RESULTS: In horses that developed acute colitis during antibiotic treatment, 18 of 43 (42%) were positive to C. difficile culture and 12 of these (28%) were positive in the cytotoxin B test. Furthermore, C. difficile was isolated from a small number of diarrhoeic mature horses (4 of 72 [6%]) with no history of antibiotic treatment, but not from 273 healthy mature horses examined or 65 horses with colic. An interesting new finding was that, in normal healthy foals age < 14 days, C. difficile was isolated from 1/3 of foals (16 of 56 [29%]). All older foals (170) except one were negative. Seven of 16 (44%) nondiarrhoeic foals treated with erythromycin or gentamicin in combination with rifampicin were also excretors of C. difficile. On studfarms, 14 of 132 (11%) outdoor soil samples were positive for C. difficile in culture, whereas only 2 of 220 (1%) soil samples from farms with mature horses were positive for C. difficile (P = < 0.001). By PCR, it was demonstrated that strains from the environment and healthy foals can serve as a potential reservoir of toxigenic C. difficile. The experimental study conducted here found that C. difficile survived in nature and indoors for at least 4 years in inoculated equine faeces. The susceptibility of 52 strains was investigated for 10 antibiotics and all were susceptible to metronidazole (MIC < or = 4 mg/l) and vancomycin (MIC < or = 2 mg/l). CONCLUSIONS: C. difficile is associated with acute colitis in mature horses, following antibiotic treatment. Furthermore, C. difficile was isolated from 1 in 3 normal healthy foals age < 14 days. POTENTIAL RELEVANCE: Strains from healthy foals and the environment can serve as a potential reservoir of toxigenic C. difficile

Characterization of Pseudomonas aeruginosa isolates from patients with urinary tract infections during antibiotic therapy.

We characterized susceptibilities and genotypes in a series of Pseudomonas aeruginosa isolates from five cases of urinary tract infections (UTIs) to evaluate clonal shifts of carbapenem resistance. In one case, a series of isolates showed different susceptibility patterns for carbapenems but an identical genotype. In another case, genotypes varied among 4 P. aeruginosa isolates from recurrent UTIs over 9 months. Although the patient had been treated with no antibiotic immediately before isolation, the susceptibility patterns for carbapenems and ceftazidime varied. Further analysis in these two cases of outer membrane protein profiles showed that loss of OprD production resulted in reduced susceptibilities to carbapenems in all of the carbapenem-resistant isolates. Loss of OprD production was likely due to oprD gene inactivation in both of cases, since the carbapenem-resistant isolates showed no cross resistance to levofloxacin and chloramphenicol compared with the carbapenem-susceptible isolates. There was another case in which all isolates showed similar susceptibility patterns for carbapenems and ceftazidime, and an identical genotype during the intermittent use of antibiotics over 5 months. In two cases, a single course of antibiotic therapy resulted in eradication of P. aeruginosa. Our results suggest that clonal shifts of carbapenem resistance in P. aeruginosa may result from loss of OprD during antibiotic treatment. Therefore, it is important for clinicians to monitor susceptibilities to antibiotics, especially carbapenems, in P. aeruginosa isolated during therapy