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Aim: The aim of this study was to investigate the short-term effect of levofloxacin on the microbiota of healthy lungs. Material and methods: Male F344 rats received either no levofloxacin (n = 9), intravenous levofloxacin (n = 12), oral levofloxacin (n = 12), or subcutaneous levofloxacin (n = 14). Rats received a clinically applicable dose (5.56 mg/kg) of levofloxacin via the assigned delivery route once daily for three days. On day four, lung tissue was collected and the lung microbiota composition was investigated using 16S ribosomal RNA gene sequencing. Results: Untreated lungs showed a microbiota dominated by bacteria of the genera Serratia . After treatment with levofloxacin, bacteria of the genus Pantoea dominated the lung microbiota. This was observed for all routes of antibiotic administration, with a significant difference compared to no-antibiotic control group (PERMANOVA: P < 0.001; homogeneity of dispersions: P = 0.656). Conclusion: Our study is the first to demonstrate the effects of levofloxacin therapy on lung microbiota in laboratory rats. Levofloxacin treatment by any route of administration leads to profound changes in the rat lung microbiota, resulting in the predominance of bacteria belonging to the genus Pantoea . Further studies regarding the role of long-term application of broad spectrum antibiotics on induction of lung, allergic and autoimmune diseases are indicated.

Background: Clinical experience and animal studies have suggested that positron emission tomography (PET) using fluorine-18-labeled fluorodeoxyglucose ((18)F-FDG) may be promising for imaging of bone infections. In this study, we aimed to establish the accuracy of (18)F-FDG PET scanning for monitoring the response to poly(lactide-co-glycolide) (PLGA) vancomycin beads for treatment of bone infection., Methods: PLGA was mixed with vancomycin and hot-compress molded to form antibiotic beads. In vitro, elution assays and bacterial inhibition tests were employed to characterize the released antibiotics. In vivo, cylindrical cavities were made in six adult male New Zealand white rabbits, and Staphylococcus aureus or saline was injected into the cavity to create a bone infection. After 2 weeks, the infection was confirmed by bacterial cultures, and the defect was filled with PLGA vancomycin beads. The treatment response was monitored by (18)F-FDG PET., Results: The biodegradable beads released high concentrations of vancomycin (well above the breakpoint sensitivity concentration) for treatment of bone infection. In bacterial inhibition tests, the diameter of the sample inhibition zone ranged from 6.5 to 10 mm, which was equivalent to 12.5-100 % relative activity. (18)F-FDG PET results showed that uncomplicated bone healing was associated with a temporary increase in (18)F-FDG uptake at 2 weeks, with return to near baseline at 6 weeks. In the infected animals, localized infection resulted in intense continuous uptake of (18)F-FDG, which was higher than that in uncomplicated healing bones. Bone infection was confirmed with positive bacterial cultures. In vancomycin-treated animals, data showed rapidly decreasing amounts of (18)F-FDG uptake after treatment., Conclusions: In vitro and in vivo analyses showed that the use of biodegradable PLGA vancomycin beads successfully eradicated S. aureus infection in damaged bone.

Unlabelled: Several studies have yielded conflicting results on the role of antibiotic prophylaxis in improving outcomes in acute necrotizing pancreatitis. A meta-analysis was carried out to investigate the impact of antibiotic prophylaxis in the incidence of infected pancreatic necrosis and mortality., Methodology: Randomized controlled trials and cohort studies investigating impact of prophylactic systemic antibiotic used in acute necrotizing pancreatitis were retrieved from online databases. An overall analysis was done with all studies (Group 1), followed by subgroup analyses with randomized controlled trials (Group 2) and cohort studies (Group 3). Risk ratios (RR) were calculated for the impact of antibiotic prophylaxis in the incidence of infected pancreatic necrosis and mortality in each group using random effects model., Results: Eleven studies involving 864 patients were included. No significant differences in the incidence of infected pancreatic necrosis were observed with prophylactic antibiotic use in all groups. Prophylactic antibiotic use was not associated with significant differences in all-cause mortality in Group 2 (RR = 0.75; p = 0.24) but was associated with a reduction in Groups 1 (RR = 0.66, p = 0.02) and 3 (RR = 0.55, p = 0.04). There was no statistical difference in the incidence of fungal infections and surgical interventions., Conclusion: Antibiotic prophylaxis does not significantly reduce the incidence of infected pancreatic necrosis but may affect all-cause mortality in acute necrotizing pancreatitis.

Use of animal manure is a main source of veterinary pharmaceuticals (VPs) in soil and groundwater through a series of migration processes. The sorption-desorption and transport of four commonly used VPs including trimethoprim (TMP), sulfapyridine, sulfameter, and sulfadimethoxine were investigated in three soil layers taken from an agricultural field in Chongming Island China and two types of aqueous solution (0.01 M CaCl2 solution and wastewater treatment plant effluent). Results from sorption-desorption experiments showed that the sorption behavior of selected VPs conformed to the Freundlich isotherm equation. TMP exhibited higher distribution coefficients (K d = 6.73-9.21) than other sulfonamides (K d = 0.03-0.47), indicating a much stronger adsorption capacity of TMP. The percentage of desorption for TMP in a range of 8-12 % is not so high to be considered significant. Low pH (

Antimicrobial resistance (R) surveillance across Asia and especially in China has documented unique patterns and mechanisms. This 2011 study reports results for 2278 isolates from 12 hospitals in China (94-216 strains/site); most from bacteremia (20.4%), pneumonias (29.1%), or skin and skin structure infections (20.9%). Samples were tested by reference broth microdilution methods, interpreted by published susceptibility (S) breakpoints. The most common species were Staphylococcus aureus (343, 45.8% MRSA), Escherichia coli (EC; 288), Pseudomonas aeruginosa (PSA; 221), Klebsiella spp. (KSP; 208), acinetobacters (ACB; 178), enterobacters (155), Streptococcus pneumoniae (SPN; 154, 46.8% penicillin-S), and enterococci (ENT; 137). Among 849 Gram-positive (GP) cocci, linezolid, tigecycline (TIG), daptomycin, and vancomycin provided best antimicrobial coverage (≥99.7% S). Resistance patterns of concern were 0.3% VISA, 15.4% teicoplanin non-S coagulase-negative staphylococci, 1.5% vancomycin-R ENT (all Enterococcus faecium), 1.9% levofloxacin-R β-haemolytic streptococci, and 35.1 and 12.7% ceftriaxone-non-S rates for SPN and viridans group streptococci, respectively. For Gram-negative bacilli, R among Enterobacteriaceae was highest against β-lactams (extended spectrum β-lactamase-phenotype strains at 73.6 and 42.8% in EC and KSP, respectively; carbapenem-R was only 2.1-4.3% with KPC and IMP type enzymes detected in KSP). The widest spectrum agents were cefoperazone/sulbactam (79.5-86.1%), piperacillin/tazobactam (88.9-92.0%), TIG (98.6-100%), amikacin (AMK; 91.8-93.7%), and meropenem (95.7-97.1% S). PSA was most inhibited by AMK (90.5% S) and colistin (COL; 99.5%), with cefepime (67.9%) best among the tested β-lactams. Only COL (100% S) and TIG (MIC90, 2 μg/mL) showed significant potencies against ACB. In conclusion, R among pathogens from 12 Chinese hospitals illustrates several agents active against GP pathogens, but more serious R problems were noted among Enterobacteriaceae, PSA, and ACB. Combination treatment for the latter multidrug-R strains appears necessary, guided by local antibiograms and national surveillance results applying reference methods., (© 2013.)

The Regional Resistance Surveillance program monitored susceptibility rates and developing resistance by geographic region, including 12 Asia-Pacific (APAC) countries. Reference broth microdilution methods for susceptibility/interpretations were applied, processing 5,053 strains. Among Staphylococcus aureus isolates (37% methicillin-resistant S. aureus [MRSA], highest in South Korea [73%]), linezolid (LZD), tigecycline (TIG), and vancomycin were 100% active, but 33 and 34% of strains were levofloxacin (LEV) or macrolide resistant, respectively. Streptococcus pneumoniae was most resistant to β-lactams and macrolides (45%) but was LZD, LEV, and TIG susceptible (>98%). Extended-spectrum β-lactamase (ESBL) phenotype rates in Escherichia coli and Klebsiella spp. were 48 and 47%, respectively, and were highest in Taiwan, at 75 to 91%. The best anti-ESBL-phenotype agents were amikacin (81 to 96% susceptible), colistin (COL; >98%), TIG (>98%), and carbapenems (81 to 97%). Pseudomonas aeruginosa showed ≥20% resistance to all drugs except COL (99% susceptible). In conclusion, endemic evolving antimicrobial resistances in APAC nations show compromised roles for many commonly used antimicrobials.

Whilst studies have shown that antimicrobial stewardship programmes (ASPs) can effectively reduce antibiotic utilisation, cost of care and even antimicrobial resistance rates, ASPs should avoid the perception that the goal is primarily to reduce antibiotic purchases and costs, instead of focusing on improving the quality of care. In addition, to address the concern of primary physicians who deemed that ASPs' choices of antibiotics were often inadequate, the impact of ASPs on patient safety should be monitored and evaluated. The aim of this study was to analyse the impact of ASP interventions on patient safety in Singapore General Hospital (SGH), a 1559-bed, large, acute, tertiary-care hospital in Singapore. A retrospective database review of data on ASP interventions issued between October 2008 and September 2010 was performed. The database maintained by the ASP team detailed patients' demographic data as well as outcomes of issued interventions. The ASP recommended 1256 interventions in a total of 1249 admissions in six departments. Shorter average length of stay (mean ± standard deviation 19.4 ± 19.9 days vs. 24.2 ± 24.2 days) was observed among patients of physicians who accepted ASP suggestions compared with patients of physicians who rejected ASP interventions (P<0.01). ASP interventions did not alter all-cause mortality (P=0.191). In addition, the number of infection-related re-admissions (P<0.001) and the 14-day re-infection rate (P=0.009) were higher among patients whose physicians rejected ASP interventions. In conclusion, interventions recommended by the ASP in SGH were safe and were associated with a reduction in the duration of hospital stay, 14-day re-infection rate and infection-related re-admissions., (Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

A solid-phase extraction (SPE)-high performance liquid chromatography (HPLC) method has been developed for simultaneous determination of 10 sulfonamide antibiotics in water. The analytes were first enriched and purified through a PEP solid-phase extraction column, and eluted with acetonitrile-dichloromethane solution (2: 1, V/V), then detected by a HPLC with a UV detector. The detection wavelength was 268 nm and the column temperature was 33 degrees C, using gradient elution process with acetonitrile - 0.4% acetic acid/water (V/V) as the mobile phase to achieve baseline separations of these 10 analytes. The linearity range was 10 - 2 000 microg x L(-1). The recovery ranges of standard addition for deionized water and real water samples were 73.4% - 95.6% and 70.2% - 92.5%, respectively (except for sulfonamide, were 8.5% and 8.0%). The limit of detection was 1.42-7.25 ng x L(-1). Application of this method for parts of Huangpu River in Shanghai, surface water and groundwater in Chongming Island showed that sulfonamide antibiotics were detected in different frequencies in different aqueous environments, with the concentration range of 13.3 - 241.5 ng x L(-1), proving this method is easy, rapid, sensitive and efficient to meet the needs of actual work.

Osteomyelitis has been one of the most common causes of post-operative problems and complications despite the advances in surgical techniques and the availability of newly developed antibiotics. Local antibiotic and growth factor delivery devices for treatment of various surgical infections have been studied recently, especially in the case of orthopedic infections. The report was to develop novel solvent-free biodegradable capsules for antibiotics and growth factors delivery. To fabricate a biodegradable capsule, polylactide-polyglycolide copolymers were pre-mixed with vancomycin. The mixture was then compression molded and sintered to form a cylinder with a cover of 8 mm in diameter. After the addition of 1 and 10 microg recombinant bone morphogenetic protein (rhBMP-2) into the core, an ultrasonic welder was used to seal the capsules. An elution method was employed to characterize the in vitro release characteristics of the antibiotics and the rhBMP-2 over a 30-day period. The HPLC analysis and the bacterial inhibition test showed that biodegradable capsules released high concentrations and activity of vancomycin (well above the minimum inhibition concentration) in vitro for the period of time needed to treat bone infection; i.e. 4-6 weeks. In addition, the results of ELISA and ALP tests also suggested that the capsules released active rhBMP-2 for up to 30 days. By adopting this novel technique, we will be able to fabricate biodegradable capsules of various medicines for long-term drug deliveries.

This study presents a novel biodegradable alginate delivery system for antibiotics and bone cells to treat infected bone defects. About 2 x 10(7) New Zealand rabbit mesenchymal stem cells (MSCs) and 5 mL vancomycin solution (50 mg/mL) were added to 5 mL of 2.5% (w/v) sodium alginate solution to form biodegradable antibiotic and MSCs alginate beads 3 mm in diameter. The alginate beads were then cultured in an osteogenic medium for 14 days. The profiles of antibiotics released from the alginate beads were evaluated using the method of high performance liquid chromatography (HPLC). The expression of osteogenic genes, including Cbfa1 and osteopontin, in the alginate beads was determined by reverse transcription-polymerase chain reaction (RT-PCR) analysis. The alkaline phosphatase activity, calcium level, and mineral deposition of the cultured cells within the alginate beads were assessed. Analytical results demonstrated that the concentrations of vancomycin eluted from the alginate beads were, for 14 days, well above the minimal inhibitory concentration of Staphylococcus aureus. Osteopontin and mRNA of Cbfa1 were detected and increased alkaline phosphatase activity and calcium levels were noted, as was a substantial mineral deposition in cultured MSCs. The PKH 26-labeled MSCs and vancomycin alginate beads were implanted in rabbit bony cavities for in vivo analysis. Implanted PKH 26-labeled MSCs were identified in the newly formed bony trabeculae in all specimens at 2 and 4 months after implantation and there was abundant mineral deposition. The results of in vitro study demonstrated sustained elution of vancomycin from the alginate carrier for 14 days and good osteogenic differentiation of cultured MSCs in the alginate carrier matrix. The results of in vivo study demonstrated the implanted MSCs participating in new bone formation. Based on experimental evidence, development of a biodegradable alginate carrier system for antibiotics and bone cells is possible, providing a potential treatment procedure for infected bone defects., ((c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The authors investigated the lyophilized poly-L-lysine-coated alginate antibiotic delivery system in vivo for the treatment of musculoskeletal infections. The sodium alginate was mixed with vancomycin, coated with poly-L-lysine and lyophilized to form 3 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 minimal inhibitory concentration of Staphylococcus aureus for 21 days. The release was most marked during the first two days. The diameters of sample inhibition zone ranged from 8 to 16 mm, the relative activity of vancomycin ranged from 12.5% to 100%. The blood level of vancomycin reached its peak (46.0 mg/l) two days after implantation and fell to 3.2 mg/l at two weeks. It was undetectable after three weeks. There was no increase in the concentration of blood urea nitrogen and serum creatinine after the implantation. Histological observations showed that bead materials were biodegradable, resorbed slowly and only cause mild host reaction. This study offers a biodegradable delivery system of antibiotics to treat musculoskeletal infections.

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.

The current delivery system of antibiotics for the treatment of osteomyelitis uses polymethylmethacrylate (PMMA) beads as a local drug-release agent. The nonbiodegradable nature of the PMMA, however, necessitates a second operation to remove the beads. This article explores the alternative of using biodegradable polymers as antibiotic beads for a long-term drug release in vivo. To manufacture an antibiotic bead, lactide-glycolide copolymers were mixed with vancomycin. The mixture was compressed and sintered at 55 degrees C to form beads 8 mm in diameter. An in vivo animal model was proposed to characterize the elution rate of antibiotic over a 55-day period. Biodegradable beads released high concentrations of antibiotic (well above the breakpoint sensitivity concentration) in vivo for the period of time needed to treat bone infection; that is, 4-6 weeks. A bacterial inhibition test was also carried out to determine the relative activity of the released antibiotics. The diameter of the sample inhibition zone ranged from 8 to 18 mm, which is equivalent to 9.1 to 100% of relative activity. In addition, the antibiotic concentration of systemic blood was found to be very low. Antibiotic-impregnated biodegradable beads may have a potential role in the prevention and management of surgical infections., (Copyright 2002 Wiley Periodicals, Inc.)

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.

Objective: The authors investigated the calcium alginate dressing as a drug-delivery system for the treatment of various surgical infections., Methods: Cytotoxicity of the calcium alginate dressing to fibroblasts and HeLa cells was evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MITT) colorimetric assay. The calcium alginate dressing was mixed with vancomycin, and lyophilized or not lyophilized to form two types of antibiotic dressings. The antibiotic dressings were placed in 2 mL of phosphate buffered saline (PBS) or in PBS containing 0.01% calcium ions, and incubated at 37 degrees C. The PBS was changed daily, and the removed solutions were stored at -70 degrees C until the antibiotic concentration in each sample was determined by high performance liquid chromatography assay., Results: The results suggested that the antibiotic dressings present no obvious toxic risk to their use as a drug-delivery system. The concentration of vancomycin in each sample was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial kill. ing and resistance to the antibiotic) for more than 14 days. The release was most marked during the first 48 hours. The concentration of calcium ions in PBS and the lyophilization of the manufacture process of antibiotic dressings prolonged the antibiotic diffusion duration. The diameter of the sample inhibition zone ranged from 10 to 11 mm, and the relative activity of vancomycin ranged from 62.88% to 92.18%., Conclusion: All antibiotic dressings released bactericidal concentrations of the antibiotics in vitro for the period of time needed to treat surgical infections. This study offers a convenient method to meet the specific antibiotic requirement for different patients.

Antibiotic beads have been used as a drug delivery system 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 five types of biodegradable antibiotic beads. The beads were placed in 1 mL of phosphate buffered saline and incubated at 37 degrees C. The phosphate buffered saline was changed daily, and the removed buffer solutions were stored at -70 degrees C until the antibiotic concentration in each sample was determined by high performance liquid chromatography system assay. The concentration of vancomycin in each sample was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial killing and resistance to the antibiotic) for more than 32 days. The release was most marked during the first 48 hours. All copolymer 50:50 poly(DI lactide):co-glycolide biodegradable beads released high concentrations of the antibiotics in vitro for the time needed to treat bone infections (4 to 6 weeks). The diameter of the sample inhibition zone ranged from 6.5 mm to 10 mm, and the relative activity of vancomycin ranged from 12.5% to 100%. Copolymers with low heat of formation temperatures are required for making a controlled release system to prevent antibiotic decomposition, which occurs when using the hot compressing molded method. The rate and duration of release from the antibiotic beads can be adjusted by varying the diameter of the beads. This offers a convenient method to adjust the release rate to meet the specific antibiotic requirements for different patients.

The current antibiotics delivery system for orthopedic infection treatment uses polymethylmethacrylate (PMMA) beads as a drug release. However the nonbiodegradable nature of the PMMA necessitates a second operation to remove the beads. This article explores the alternative of using biodegradable polymers as antibiotic beads for a long-term drug release. The effect of different processing factors on the release rate of the beads was investigated. To manufacture an antibiotic bead, polylactide-polyglycolide copolymers were mixed with vancomycin. The mixture was compressed and sintered at 55 degrees C to form beads of different sizes. An elution method was employed to characterize the release rate of antibiotic over a 35-day period at 37 degrees C. Biodegradable beads released high concentrations of antibiotic (well above the breakpoint sensitivity concentration) in vitro for the period of time needed to treat bone infection; i.e., 4-6 weeks. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The diameter of the sample inhibition zone ranged from 6.5-10 mm, which is equivalent to 12.5-100% of relative activity. By changing the processing parameters, we were able to control the release rate of the beads. This provides advantages of meeting the specific antibiotics requirement for patients with various surgical infections., (Copyright 1999 John Wiley & Sons, Inc.)