Use Of Local Antibiotics Research Articles

Adverse consequences of neonatal antibiotic exposure.

Antibiotics have not only saved lives and improved outcomes, but they also influence the evolving microbiome. This review summarizes reports on neonatal infections and variation in antibiotic utilization, discusses the emergence of resistant organisms, and presents data from human neonates and animal models demonstrating the impact of antibiotics on the microbiome, and how microbiome alterations impact health. The importance of antibiotic stewardship is also discussed. Infections increase neonatal morbidity and mortality. Furthermore, the clinical presentation of infections can be subtle, prompting clinicians to empirically start antibiotics when infection is a possibility. Antibiotic-resistant infections are a growing problem. Cohort studies have identified extensive center variations in antibiotic usage and associations between antibiotic exposures and outcomes. Studies of antibiotic-induced microbiome alterations and downstream effects on the developing immune system have increased our understanding of the mechanisms underlying the associations between antibiotics and adverse outcomes. The emergence of resistant microorganisms and recent evidence linking antibiotic practice variations with health outcomes has led to the initiation of antibiotic stewardship programs. The review encourages practitioners to assess local antibiotic use with regard to local microbiology, and to adopt steps to reduce infections and use antibiotics wisely.

Terapia antibiotica e antimicrobica locale nella terapia parodontale. Revisione della letteratura

ObjectivesThis review is intended to present a narrative report of the latest scientific papers published in the literature, concerning the use of local antibiotics and antimicrobial agents in addition to causal periodontal therapy in order to provide an update on the latest scientific evidence about the benefits, limitations and clinical results obtained by the use of such substances. Materials and methodsA narrative review of the literature has been conducted, using PubMed, Medline and Google Scholar including articles published in peer-reviewed journals between January 2009 and December 2014. The following keywords were used: “local delivery antimicrobials”, “local delivery antibiotics”, “local delivery AND periodontitis”, “local antibiotics AND periodontitis”, “local antimicrobials AND periodontitis” ResultsFrom this review we can infer that the use of local antibiotics or antimicrobial agents delivers significant benefits in periodontal therapy. Although it cannot replace the mechanical therapy, it is a useful aid, avoiding many of the side effects that systemic antibiotic therapy may involve. ConclusionsThe local antibiotic and antimicrobial therapy is effective in the treatment of periodontal disease when used in addition to the mechanical therapy. In the opinion of the authors, the use of such agents should be preferred in cases of localized acute lesions or individual sites that do not respond to the causal therapy, always following a thorough scaling and root planing of the areas affected by the pathological process. However, to date, it is not possible to establish guidelines on the use of these agents given the heterogeneity of the protocols used in the various studies and the lack of consensus accepted by the scientific community.

Current trends in local antibacterial therapy of periprosthetic infection and osteomyelitis

The rational use of antibiotics in the treatment of orthopedic infection still presents a significant problem. Local antibiotic delivery systems enable to achieve effective concentrations of drugs in the focus of bone infection without the development of toxicity. It is the important accompaniment to systemic antibiotics in the treatment of periprosthetic infection and osteomyelitis. The data collected through the PubMed and eLIBRARY databases (http://www.ncbi.nlm. nih.gov/pubmed, 1995-2015; http://elibrary.ru, 2005-2015 years) present the information about bone substitutes used for local antibiotic therapy in scientific investigations and in clinical practice. The information is submitted in accordance with the groups of materials: cements based on polymethylmethacrylate, bone grafts, demineralized bone matrix, bioceramics, natural and synthetic polymers, combined antibiotic delivery systems. The majority of these materials have only been studied experimentally and only a limited range of them is registered for use in clinical practice. Informing orthopedic surgeons about current methods of local antibiotic use is the key to the development of a modern integrated approach to the therapy of infectious complications after orthopedic surgery.

Management of peri-implant mucositis and peri-implantitis.

Peri-implant diseases are defined as inflammatory lesions of the surrounding peri-implant tissues and include peri-implant mucositis (an inflammatory lesion limited to the surrounding mucosa of an implant) and peri-implantitis (an inflammatory lesion of the mucosa that affects the supporting bone with resulting loss of osseointegration). This review aims to describe the different approaches to manage both entities and to provide a critical evaluation of the evidence available on their efficacy. Therapy of peri-implant mucositis and nonsurgical therapy of peri-implantitis usually involve mechanical debridement of the implant surface using curettes, ultrasonic devices, air-abrasive devices or lasers, with or without the adjunctive use of local antibiotics or antiseptics. The efficacy of these therapies has been demonstrated for mucositis: controlled clinical trials show an improvement in clinical parameters, especially in bleeding on probing. For peri-implantitis, the results are limited, especially in terms of probing pocket-depth reduction. Surgical therapy of peri-implantitis is indicated when nonsurgical therapy fails to control the inflammatory changes. Selection of the surgical technique should be based on the characteristics of the peri-implant lesion. In the presence of deep circumferential and intrabony defects, surgical interventions should aim to provide thorough debridement, implant-surface decontamination and defect reconstruction. In the presence of defects without clear bony walls or with a predominant suprabony component, the aim of the surgical intervention should be the thorough debridement and the repositioning of the marginal mucosa to enable the patient to perform effective oral-hygiene practices, although this aim may compromise the esthetic result of the implant-supported restoration.

Treatment of acute periprosthetic infections with prosthesis retention: Review of current concepts.

Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty, occurring in approximately 1%-2% of all cases. With growing populations and increasing age, PJI will have a growing effect on health care costs. Many risk factors have been identified that increase the risk of developing PJI, including obesity, immune system deficiencies, malignancy, previous surgery of the same joint and longer operating time. Acute PJI occurs either postoperatively (4 wk to 3 mo after initial arthroplasty, depending on the classification system), or via hematogenous spreading after a period in which the prosthesis had functioned properly. Diagnosis and the choice of treatment are the cornerstones to success. Although different definitions for PJI have been used in the past, most are more or less similar and include the presence of a sinus tract, blood infection values, synovial white blood cell count, signs of infection on histopathological analysis and one or more positive culture results. Debridement, antibiotics and implant retention (DAIR) is the primary treatment for acute PJI, and should be performed as soon as possible after the development of symptoms. Success rates differ, but most studies report success rates of around 60%-80%. Whether single or multiple debridement procedures are more successful remains unclear. The use of local antibiotics in addition to the administration of systemic antibiotic agents is also subject to debate, and its pro's and con's should be carefully considered. Systemic treatment, based on culture results, is of importance for all PJI treatments. Additionally, rifampin should be given in Staphylococcal PJIs, unless all foreign material is removed. The most important factors contributing to treatment failure are longer duration of symptoms, a longer time after initial arthroplasty, the need for more debridement procedures, the retention of exchangeable components, and PJI caused by Staphylococcus (aureus or coagulase negative). If DAIR treatment is unsuccessful, the following treatment option should be based on the patient health status and his or her expectations. For the best functional outcome, one- or two-stage revision should be performed after DAIR failure. In conclusion, DAIR is the obvious choice for treatment of acute PJI, with good success rates in selected patients.

Surgical debridement to optimise wound conditions and healing

Different treatment strategies are available for bone, joint and soft tissue infections, including use of local antibiotics; negative pressure wound therapy; one-stage, two-stage or multi-stage revisions; or open wound therapy. All methods have one principle in common: adequate surgical debridement is the prerequisite for successful treatment of bone, joint and soft tissue infections. According to the different textures of healthy, infected or necrotic tissue, special techniques are used. In this article we will describe the clinical presentation of necrotic and non-vital tissue in skin, soft tissue and bone and appropriate techniques of debridement.

Vancomycin Prophylaxis of Surgical Site Infection in Clean Orthopedic Surgery

Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has been recognized as a public health concern since the mid-1990s. Because of the increase in reports of this pathogen, it has become increasingly tempting for clinicians to provide prophylaxis against this entity using antibiotics known to be effective against MRSA. The goal of this study was to assess the use of MRSA prophylaxis to determine whether it is safe and effective. A systematic search of the literature was performed to identify articles that examined the use of vancomycin in clean orthopedic surgery. Infection rates and adverse events were extracted, and the data were aggregated and analyzed using a DerSimonian and Laird random effects model. Publication bias and study quality were also assessed. No benefit of parenteral administration of vancomycin was identified. Local, vancomycin-impregnated cement and powder are associated with lower infection rates. Few adverse events occurred, and most of those that occurred involved infusion rate.Cost, resistance, and side effects are concerns in using vancomycin therapy in addition to standard antibiotic prophylaxis. Given the lack of efficacy of intravenous vancomycin, the authors do not recommend its routine use in clean orthopedic surgery. However, local administration appears to be safe and effective. The data are most compelling in orthopedic spine surgery in which a patient without prophylaxis is more than 4 times as likely to have a deep postoperative wound infection compared with a patient who received local vancomycin. The authors recommend the use of local antibiotics when possible in clean orthopedic surgery.

The use of Antimicrobial-Impregnated PMMA to Manage Periprosthetic Infections: Controversial Issues and the Latest Developments

Despite improvements in intraoperative antimicrobial procedures, in surgical techniques and in implant design for joint replacement, periprosthetic infection after arthroplasty is still one of the most challenging problems encountered by orthopedic surgeons. Systemic antibiotics are not sufficiently effective to eradicate such deep infections because of the impaired blood circulation and low antibiotic concentration at the implantation site. As a local drug delivery system, antibiotic-impregnated PMMA (polymethylmethacrylate) bone cements have been widely used for prophylaxis or treatment of deep infections after total joint replacement. However, the effectiveness of antibiotic-loaded PMMA in preventing infections after arthroplasty is still controversial. Furthermore, the outcomes of established deep infections treated with this technique are not consistent. The local use of antibiotics has led to the emergence of antibiotic-resistant bacterial strains and has adverse effects on the function of osteogenic cells. Recently, many efforts have been made to identify new antibacterial agents that can be loaded into PMMA. These antimicrobial agents should exhibit good antibacterial activity against antibiotic-resistant strains and should simultaneously enhance osteointegration between the PMMA and the bone tissue. PMMA loaded with chitosan or chitosan derivatives has been demonstrated to induce improved osteogenic activity and to exhibit antibacterial activity in a preclinical study.

No reliable evidence suggesting what is the most effective interventions for treating peri-implantitis

The Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase databases were searched. Authors of trials were contacted as were more than 55 dental implant manufacturers and an Internet discussion group to find unpublished or ongoing randomised controlled trials (RCTs). All randomised controlled trials (RCTs) evaluating interventions to treat peri-implantitis, including studies with parallel group and split-mouth designs. Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two review authors. Results were expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals (CI). Heterogeneity was to be investigated including both clinical and methodological factors. Nine studies were included with follow-up ranging from three months to four years. They compared different non-surgical interventions (five trials); adjunctive treatments to non-surgical interventions (one trial); different surgical interventions (two trials); adjunctive treatments to surgical interventions (one trial). No study was judged to be at low risk of bias. Statistically significant differences were observed in two small single trials judged to be at unclear or high risk of bias. After four months, adjunctive local antibiotics to manual debridement in patients who lost at least 50% of the bone around implants showed improved mean probing attachment levels (PAL) of 0.61 mm (95% confidence interval (CI) 0.40 to 0.82) and reduced probing pockets depths (PPD) of 0.59 mm (95% CI 0.39 to 0.79). After four years, patients with peri-implant infrabony defects > 3 mm treated with Bio-Oss and resorbable barriers gained 1.4 mm more PAL (95%CI 0.24 to 2.56) and 1.4 mm PPD (95%CI 0.81 to 1.99) than patients treated with a nanocrystalline hydroxyapatite. There is no reliable evidence suggesting which could be the most effective interventions for treating peri-implantitis. This is not to say that currently used interventions are not effective. A single small trial at unclear risk of bias showed the use of local antibiotics in addition to manual subgingival debridement was associated with a 0.6 mm additional improvement for PAL and PPD over a four-month period in patients affected by severe forms of peri-implantitis. Another small single trial at high risk of bias showed that after four years, improved PAL and PPD of about 1.4 mm were obtained when using Bio-Oss with resorbable barriers compared to a nanocrystalline hydroxyapatite in peri-implant infrabony defects. There is no evidence from four trials that the more complex and expensive therapies were more beneficial than the control therapies which basically consisted of simple subgingival mechanical debridement. Follow-up longer than one year suggested recurrence of periimplantitis in up to 100% of the treated cases for some of the tested interventions. As this can be a chronic disease, re-treatment may be necessary. Larger well-designed RCTs with follow-up longer than one year are needed.

Interventions for replacing missing teeth: treatment of peri-implantitis

One of the key factors for the long-term success of oral implants is the maintenance of healthy tissues around them. Bacterial plaque accumulation induces inflammatory changes in the soft tissues surrounding oral implants and it may lead to their progressive destruction (peri-implantitis) and ultimately to implant failure. Different treatment strategies for peri-implantitis have been suggested, however it is unclear which are the most effective. To identify the most effective interventions for treating peri-implantitis around osseointegrated dental implants. We searched the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE and EMBASE. Handsearching included several dental journals. We checked the bibliographies of the identified randomised controlled trials (RCTs) and relevant review articles for studies outside the handsearched journals. We wrote to authors of all identified RCTs, to more than 55 dental implant manufacturers and an Internet discussion group to find unpublished or ongoing RCTs. No language restrictions were applied. The last electronic search was conducted on 9 June 2011. All RCTs comparing agents or interventions for treating peri-implantitis around dental implants. Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two review authors. We contacted the authors for missing information. Results were expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals (CI). Heterogeneity was to be investigated including both clinical and methodological factors. Fifteen eligible trials were identified, but six were excluded. The following interventions were compared in the nine included studies: different non-surgical interventions (five trials); adjunctive treatments to non-surgical interventions (one trial); different surgical interventions (two trials); adjunctive treatments to surgical interventions (one trial). Follow-up ranged from 3 months to 4 years. No study was judged to be at low risk of bias.Statistically significant differences were observed in two small single trials judged to be at unclear or high risk of bias. After 4 months, adjunctive local antibiotics to manual debridement in patients who lost at least 50% of the bone around implants showed improved mean probing attachment levels (PAL) of 0.61 mm (95% confidence interval (CI) 0.40 to 0.82) and reduced probing pockets depths (PPD) of 0.59 mm (95% CI 0.39 to 0.79). After 4 years, patients with peri-implant infrabony defects > 3 mm treated with Bio-Oss and resorbable barriers gained 1.4 mm more PAL (95% CI 0.24 to 2.56) and 1.4 mm PPD (95% CI 0.81 to 1.99) than patients treated with a nanocrystalline hydroxyapatite. There is no reliable evidence suggesting which could be the most effective interventions for treating peri-implantitis. This is not to say that currently used interventions are not effective.A single small trial at unclear risk of bias showed the use of local antibiotics in addition to manual subgingival debridement was associated with a 0.6 mm additional improvement for PAL and PPD over a 4-month period in patients affected by severe forms of peri-implantitis. Another small single trial at high risk of bias showed that after 4 years, improved PAL and PPD of about 1.4 mm were obtained when using Bio-Oss with resorbable barriers compared to a nanocrystalline hydroxyapatite in peri-implant infrabony defects. There is no evidence from four trials that the more complex and expensive therapies were more beneficial than the control therapies which basically consisted of simple subgingival mechanical debridement. Follow-up longer than 1 year suggested recurrence of peri-implantitis in up to 100% of the treated cases for some of the tested interventions. As this can be a chronic disease, re-treatment may be necessary. Larger well-designed RCTs with follow-up longer than 1 year are needed.

Prevalence of Gram-negative bacilli resistance in adult critically ill patients at admission screening

Nosocomial infections in critically ill patients are increasing and they are often due to multidrug-resistant Gram-negative bacilli (GNB). Emerging resistance in common nosocomial pathogens is usually related to local antibiotic use. Gentamicin is the first-line empiric antibiotic for hospital-acquired infections in St Thomas' Hospital ICUs. No decontamination therapy for GNBs is employed, but rectal and nose swabs are routinely taken from patients on admission to screen for resistance in GNB. This informs the choice of antimicrobial therapy in the event of nosocomial infection during the patient's stay. We describe antibiotic resistance rates in GNB isolates at admission in critically ill adult patients over 8 years.

Fabrication of cefuroxime-impregnated calcium sulfate: Polycaprolactone composite implant for osteomyelitis

Osteomyelitis is characterized as an inflammatory bone disease caused by pyrogenic bacteria. As oral bioavailabilities of antibiotics are low, a regimen of 6 weeks of intravenous antibiotic is necessary for adequate therapy. Although the dose of antibiotic administered systemically is high, therapeutically effective drug concentrations are not always achieved at the site of infection. This problem can be overcome by the use of local antibiotics from a biodegradable implant for chronic osteomyelitis that can deliver the drug at least for 6 weeks.The implant delivers high antibiotic concentration at tissue levels, obliterates dead space, aids bone repair and does not need to be removed. The aim of this study was to develop and evaluate a calcium sulfate and polycaprolactone (PCL)-based composite biodegradable implantable delivery system of cefuroxime for the localized treatment of osteomyelitis that can deliver the drug for at least 6 weeks.The PCL and calcium sulfate composite system has not been studied yet. Interaction studies were carried out to check any incompatibility between the ingredients. Implants were prepared by a modified fabrication technique to avoid solvent use. The prepared implants were evaluated for various in vitro parameters like dimensions, hardness, tensile strength, drug release profile, sterility test and morphological changes in pellet before and after drug release. The pellets were also tested for microbiological efficacy and compared with a plain drug solution in different concentrations. Developed pellets are regular in shape and size with good tensile strength. The release profile displayed drug levels above the minimum inhibitory concentration continuously for up to 2 months. A wide zone of inhibition by the pellet against Staphylococcus aureus as compared with the drug solution proves its efficacy in the treatment of osteomyelitis. Results show that the developed calcium sulfate and PCL-based composite biodegradable implantable delivery system of cefuroxime is a good alternate system and can deliver the drug for more than 6 weeks, maintaining an adequate inhibitory concentration at the site.

Cefoperazone sodium impregnated polycaprolactone composite implant for osteomyelitis

The use of local antibiotics from a biodegradable implant for chronic osteomyelitis is an attractive alternative. The implant delivers high antibiotic concentration at tissue levels, obliterates dead space, aids bone repair and does not need to be removed. The purpose of this paper is to develop and evaluate a calcium sulphate and polycaprolactone based composite biodegradable implantable delivery system of cefoperazone sodium. Implants were prepared by modified fabrication technique to avoid solvent use. Interaction studies were carried out to check any incompatibility between ingredients. Prepared implants were evaluated for various in vitro parameters like dimensions, hardness, tensile strength, drug release profile and sterility. Morphological changes in pellet before and after drug release were evaluated by scanning electron microscopy. The pellet were also tested for microbiological efficacy and compared with plain drug solution in different concentrations. Developed pellets are regular in shape and size with good tensile strength. The release profile displayed drug levels above MIC continuously up to 2 months. Wide zone of inhibition by pellet against Staph. aureus as compared to drug solution proves its efficacy in treatment of osteomyelitis.

Epidural adhesiolysis complicated by cefazolin-induced status epilepticus: Two cases

Cefazolin is a strong epileptogenic agent. We describe two patients presenting with status epilepticus, apparently caused by intrathecal leakage of cefazolin via incidental dural puncture during spinal epidural adhesiolysis. Our cases suggest that the local use of antibiotics, particularly cefazolin, in the form of a mixture with contrast medium during a spinal procedure is not advisable, because of the possible incidental intrathecal leakage and the high convulsive potential of the antibiotics.

Interventions for replacing missing teeth: treatment of perimplantitis

Abstract Background: One of the key factors for the long‐term success of oral implants is the maintenance of healthy tissues around them. Bacterial plaque accumulation induces inflammatory changes in the soft tissues surrounding oral implants and it may lead to their progressive destruction (perimplantitis) and ultimately to implant failure. Different treatment strategies for perimplantitis have been suggested, however it is unclear which are the most effective. Objectives: To identify the most effective interventions for treating perimplantitis around osseointegrated dental implants. Search strategy: We searched the Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Handsearching included several dental journals. We checked the bibliographies of the identified randomized controlled trials (RCTs) and relevant review articles for studies outside the handsearched journals. We wrote to authors of all identified RCTs, to more than 55 oral implant manufacturers and an Internet discussion group to find unpublished or ongoing RCTs. No language restrictions were applied. The last electronic search was conducted on 15 March 2006. Selection criteria: All RCTs of oral implants comparing agents or interventions for treating perimplantitis around dental implants. Data collection and analysis: Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two review authors. We contacted the authors for missing information. Results were expressed as random‐effects models using weighted mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals (CI). Heterogeneity was to be investigated including both clinical and methodological factors. Main results: Seven eligible trials were identified, but two were excluded. The following procedures were tested: (1) use of local antibiotics versus ultrasonic debridement; (2) benefits of adjunctive local antibiotics to debridement; (3) different techniques of subgingival debridement; (4) laser versus manual debridement and chlorhexidine irrigation/gel; (5) systemic antibiotics plus resective surgery plus two different local antibiotics with and without implant surface smoothening. Follow up ranged from 3 months to 2 years. No meta‐analysis was conducted due to different interventions tested and outcomes used. No side effects occurred in any of the trials. The only significant statistically differences were observed in a 4‐month follow‐up RCT evaluating the use of adjunctive local antibiotics to manual debridement in patients having lost at least 50% of the supporting bone around the implants. There were improved probing attachment levels (PAL) mean differences of 0.61mm (95% CI 0.40 to 0.82), and reduced probing pockets depths (PPD) mean differences of 0.59mm (95% CI 0.39 to 0.79) in those patients receiving adjunctive local antibiotics. This trial was judged to be at high risk of bias. Authors' conclusions: There is no reliable evidence suggesting which could be the most effective interventions for treating perimplantitis. This is not to say that currently used interventions are not effective. However, the use of local antibiotics in addition to manual subgingival debridement was associated with a 0.6mm additional improvement for PAL and PPD over a 4‐month period in patients associated with severe forms of perimplantitis. In three trials, the control therapy which basically consisted of a simple subgingival mechanical debridement seemed to be sufficient to achieve results similar to the more complex and expensive therapies. Smoothening of rough implant surfaces was not associated with statistically significant improvements of the clinical outcomes. However, sample sizes were small, therefore these conclusions have to be considered with great caution. More well‐designed RCTs are needed. Plain language summary: As with natural teeth, dental implants can be lost due to gum disease (perimplantitis). This review looked at which are the most effective treatments to arrest perimplantitis Five studies were included in the review and evaluated five different treatment modalities. In one small study of short duration (4 months) it was shown that the use of locally applied antibiotics in addition to the deep manual cleaning of the diseased implants decreased the depth of the pockets around the implants of an additional 0.6mm in patients affected by severe forms of perimplantitis. In conclusion, at present, there is no reliable evidence to determine which is the most effective way to treat perimplantitis. This is not to say that currently used interventions are not effective. The majority of trials testing more complex and expensive therapies did not show any statistically or clinically significant advantages over the deep mechanical cleaning around the affected implants.

Local use of antibiotics and their input and fate in a small sewage treatment plant – significance of balancing and analysis on a local scale vs. nationwide scale

AbstractMost antibiotics are only partially metabolised by patients before being discharged into the municipal sewage system along with patient excreta. Studies have shown that the majority of antibiotics pass through sewage treatment and are then released into the environment. Accordingly, investigations conducted in various countries have detected a number of antibiotics in the low μg or ng per litre range in different environmental compartments. Studies connecting mass balances of use on a local scale and of input and analysis of the antibiotic concentrations present in municipal sewage treatment plants are scarce. Data on local use of antibiotics and their relation to nationwide consumption are not available. This study investigated the use, input, and fate of antibiotics on a local scale and this data were compared with the German nationwide consumption. 42 antibiotics and 15 antimycotics were used in the mass balance consideration over a period of one year. It was found that the local pattern of usage differed only little from that found nationwide. Seasonal changes were minor and the concentrations actually measured were found to be in the expected range. Differences in both the identified occurrence and the concentrations of the target compounds were observed within and between the three sampling periods.

In vitro and in vivo testing of bioabsorbable antibiotic containing bone filler for osteomyelitis treatment

The use of local antibiotics from a biodegradable implant is appealing concept for treatment of chronic osteomyelitis. Our aim was to develop a new drug delivery system based on controlled ciprofloxacin release from poly(D/L-lactide). Cylindrical composite pellets (1.0 x 0.9 mm) were manufactured from bioabsorbable poly(D/L-lactide) matrix and ciprofloxacin (7.4 wt %). In vitro studies were carried out to delineate the release profile of the antibiotic and to verify its antimicrobial activity by means of MIC testing. A long-term study in rabbits was performed to validate the release of ciprofloxacin from the composite in vivo. Therapeutic level of ciprofloxacin (>2 microg/mL) was maintained between 60 and 300 days and the concentration remained below the potentially detrimental level of 20 microg/mL in vitro. The released ciprofloxacin had retained its antimicrobial properties against common pathogens. In an exploratory long-term in vivo study with three rabbits, ciprofloxacin could not be detected from the serum after moderate filling (160 mg) of the tibia (follow-up 168 days), whereas after high dosing (a total dose of 1,000 mg in both tibias) ciprofloxacin was found temporarily at low serum concentrations (14-34 ng/mL) during the follow-up of 300 days. The bone concentrations of ciprofloxacin could be measured in all samples at 168 and 300 days. The tested copolylactide matrix seems to be a promising option in selection of resorbable carriers for sustained release of antibiotics, but the composite needs modifications to promote ciprofloxacin release during the first 60 days of implantation.

Oral rifampin for prevention of S. aureus carriage-related infections in patients with renal failure—a meta-analysis of randomized controlled trials

Rifampin has been studied as prophylaxis against Staphylococcus aureus-related infections in patients on dialysis. We performed a meta-analysis of randomized controlled trials (RCTs) that compared the effectiveness and safety of oral rifampin with another regimen or no therapy in reducing S. aureus-related infections in dialysis patients. Four RCTs evaluated oral rifampin (administered for 5 days every 3 months, or for 5 days once) as prophylaxis in dialysis patients. Oral rifampin with or without bacitracin was associated with less access-site infections with S. aureus compared with no treatment (odds ratio = 0.16, 95% confidence intervals: 0.06-0.44, 3 RCTs). There was no difference between prophylaxis with oral rifampin and topical mupirocin applied at the catheter site, for all studied outcomes, in the RCT comparing these regimens. Withdrawal from the study due to drug-related toxicity occurred in 7/107 (6.6%) of the studied patients with renal failure. Development of resistance of S. aureus to rifampin ranged from 0 to 18.2% (reported in three out of four included RCTs). Prophylactic use of oral rifampin reduces access-site infections with S. aureus in patients with renal failure undergoing dialysis. However, development of toxicity and antimicrobial resistance during the treatment with rifampin occur in considerable proportions of patients, limiting its use and supporting the guidelines that recommend the use of local antibiotics at the exit site, such as mupirocin, for these indications. The available data are rather limited and more studies should be performed to examine this important clinical question.

Use of Local Community Hospital Data for Surveillance of Antimicrobial Resistance

We sought to determine whether antimicrobial susceptibility data from a nonteaching community hospital could be used to detect statistically significant local increases in resistance among Streptococcus pneumoniae over a 5-year period. Minimum inhibitory concentrations (MICs) of penicillin and ceftriaxone from 1997-1998 were compared with those from 2000-2001. MICs of penicillin and ceftriaxone for organisms collected in a nonteaching community hospital in central Illinois were used for analysis. The hospital has 224 beds and a catchment area of approximately 40 miles. There were significant increases in MICs of penicillin and ceftriaxone between 1997-1998 and 2000-2001. The MIC of penicillin increased from 0.042 to 0.121 microg/mL (P = .001; 95% confidence interval, -1.713 to -0.388), and the MIC of ceftriaxone increased from 0.028 to 0.071 microg/mL (P = .005; 95% confidence interval, -1.353 to -0.188). There were no significant changes in the percentage of S. pneumoniae isolates that were resistant, intermediate, or susceptible to penicillin and ceftriaxone. MIC data from a community hospital can be used to detect local increases in the rate of resistance before antibiogram data show significant changes. This information is important for demonstrating to physicians the need to review local antibiotic use in the attempt to slow the development of resistant organisms in the community.

Low incidence of sepsis due to viridans streptococci in a ten‐year retrospective study of pediatric acute myeloid leukemia

Infections remain an important cause of morbidity and mortality in children with acute myeloid leukemia (AML), and particularly viridans group streptococci (VGS) sepsis. The present study, conducted between 1993 and 2003 in children with AML, sought to assess the frequency and characteristics of infectious complications (ICs), the incidence of VGS sepsis, the interest of preventive decontamination, and a possible cytarabine dose-effect on the occurrence of ICs. Medical charts of 78 children treated according to the EORTC 58921 clinical trial were analyzed retrospectively. Patients were isolated in laminar air flow rooms, received non-absorbable gut decontamination, gum decontamination with vancomycin mouthwash, and trimethoprim-sulfamethoxasole. ICs were categorized as microbiologically documented infections (MDI), clinically documented infections (CDI), or fever of unknown origin (FUO). Overall, 268 ICs occurred: 57.5% FUO, 8.5% CDI, and 34% MDI. Bloodstream infections occurred in 58 febrile episodes: Gram-positive bacteria represented 83% of the pathogens including 66.1% Staphylococcus species and 8.5% Streptococcus species (6.8% VGS), Gram-negative bacteria represented 13.5% of the pathogens and yeasts 3.5%. Five patients died of infection (6.4%). None died from bacterial infection and no case of VGS sepsis required intensive care. Invasive fungal infection was proven in four patients. Number of ICs was significantly different according to gum and gut decontamination status, and according to the cytarabine dose during the first intensification. No resistant strains were detected in spite of the use of local antibiotics. The low rate of VGS and enterobacteriaceae sepsis was probably due to the effective decontamination. Our supportive care strategy could potentially help enhance overall survival in children with AML.