Adjunctive local antibiotic therapy in the treatment of peri-implantitis II: clinical and radiographic outcomes

AIM: To monitor over 12 months clinical and radiographic changes occurring after adjunctive local delivery of minocycline microspheres for the treatment of peri-implantitis. MATERIAL AND METHODS: In 25 partially edentulous subjects, 31 implants diagnosed with peri-implantitis were treated. Three weeks after oral hygiene instruction, mechanical debridement and local antiseptic cleansing using 0.2% chlorhexidine gel, baseline (Day 0) parameters were recorded. Minocycline microspheres (Arestin) were locally delivered to each implant site with bone loss and a probing pocket depth (PPD) >or=5 mm. Rescue therapy with Arestin was allowed at Days 180 and 270 at any site exhibiting an increase in PPD>or=2 mm from the previous visit. The following clinical parameters were recorded at four sites/implant at Day 0, 10, 30, 60, 90, 180, 270 and 360: PPD, clinical attachment level (CAL), bleeding on probing (BOP) and plaque index (PlI). RESULTS: Six implants in six subjects were either rescued or exited because of persisting active peri-implantitis. Successful implants showed a statistically significant reduction in both PPD and percentage of sites with BOP between baseline and Day 360 (P<0.05). At mesial implant sites, the mean PPD reduction amounted to 1.6 mm (95% CI: 0.9-2.2 mm, P<0.001) and was accompanied by a statistically significant reduction of the BOP value (P<0.001). Binary regression analysis showed that the clinical parameters and smoking history could not discriminate between successfully treated and rescued or exited implants at any observation time point. CONCLUSION: Non-surgical mechanical treatment of peri-implantitis lesions with adjunctive local delivery of microencapsulated minocycline led to positive effects on clinical parameters up to 12 months.

Relationship between antibiotic concentration in bone and efficacy of treatment of staphylococcal osteomyelitis in rats: azithromycin compared with clindamycin and rifampin

We examined the effect of azithromycin (CP-62,993), a new oral macrolide-like antibiotic, alone and in combination with rifampin, as treatment for experimental staphylococcal osteomyelitis. Clindamycin was used as a comparison drug. Rats (n = 10 to 15 per group) were infected by direct instillation of Staphylococcus aureus into the tibial medullary cavity. After 10 days, 21-day treatments with azithromycin (50 mg/kg of body weight, once daily, by the oral route), rifampin (20 mg/kg, once daily, subcutaneously), or clindamycin (90 mg/kg, three times daily, by the oral route) were started. The drugs were used singly or in combination (azithromycin plus rifampin or clindamycin plus rifampin). Peak azithromycin concentrations in bone were > 30 times higher than levels in serum, but the drug had little effect on final bacterial titers (5.13 +/- 0.46 log10 CFU/g of bone; for controls, 6.54 +/- 0.28 log10 CFU/g). Clindamycin was more active than azithromycin (3.26 +/- 2.14 log10 CFU/g of bone; 20% of sterilized bones), but rifampin was the most active single drug (1.5 +/- 1.92 log10 CFU/g; 53% of sterilized bones). Therapy with rifampin or clindamycin alone was associated with the emergence of resistance. Rifampin plus azithromycin (0.51 +/- 1.08 log10 CFU/g of bone; 80% of sterilized bones) and rifampin plus clindamycin (0.87 +/- 1.34 log10 CFU/g of bone; 66% of sterilized bones) were the most active regimens. Thus, azithromycin is ineffective as a single drug for the treatment of experimental staphylococcal osteomyelitis, despite high levels in bone that markedly exceeded the MIC, but it may be an attractive partner drug for rifampin.

Antibiotic-Resistant Neisseria gonorrhoeae Spread Faster with More Treatment, Not More Sexual Partners.

The sexually transmitted bacterium Neisseria gonorrhoeae has developed resistance to all antibiotic classes that have been used for treatment and strains resistant to multiple antibiotic classes have evolved. In many countries, there is only one antibiotic remaining for empirical N. gonorrhoeae treatment, and antibiotic management to counteract resistance spread is urgently needed. Understanding dynamics and drivers of resistance spread can provide an improved rationale for antibiotic management. In our study, we first used antibiotic resistance surveillance data to estimate the rates at which antibiotic-resistant N. gonorrhoeae spread in two host populations, heterosexual men (HetM) and men who have sex with men (MSM). We found higher rates of spread for MSM (0.86 to 2.38 y-1, mean doubling time: 6 months) compared to HetM (0.24 to 0.86 y-1, mean doubling time: 16 months). We then developed a dynamic transmission model to reproduce the observed dynamics of N. gonorrhoeae transmission in populations of heterosexual men and women (HMW) and MSM. We parameterized the model using sexual behavior data and calibrated it to N. gonorrhoeae prevalence and incidence data. In the model, antibiotic-resistant N. gonorrhoeae spread with a median rate of 0.88 y-1 in HMW and 3.12 y-1 in MSM. These rates correspond to median doubling times of 9 (HMW) and 3 (MSM) months. Assuming no fitness costs, the model shows the difference in the host population's treatment rate rather than the difference in the number of sexual partners explains the differential spread of resistance. As higher treatment rates result in faster spread of antibiotic resistance, treatment recommendations for N. gonorrhoeae should carefully balance prevention of infection and avoidance of resistance spread.

Evaluating treatment protocols to prevent antibiotic resistance

The spread of bacteria resistant to antimicrobial agents calls for population-wide treatment strategies to delay or reverse the trend toward antibiotic resistance. Here we propose new criteria for the evaluation of the population-wide effects of treatment protocols for directly transmitted bacterial infections and discuss different usage patterns for single and multiple antibiotic therapy. A mathematical model suggests that the long-term benefit of single drug treatment from introduction of the antibiotic until a high frequency of resistance precludes its use is almost independent of the pattern of antibiotic use. When more than one antibiotic is employed, sequential use of different antibiotics in the population (“cycling”) is always inferior to treatment strategies where, at any given time, equal fractions of the population receive different antibiotics. However, treatment of all patients with a combination of antibiotics is in most cases the optimal treatment strategy.

Risk-based approach to the management of on-site wastewater treatment facilities

Background On-site wastewater treatment system (OWTS) siting, design and management has traditionally been based on site specific conditions with little regard to the surrounding environment or the cumulative effect of other systems in the environment. The general approach has been to apply the same framework of standards and regulations to all sites equally, regardless of the sensitivity, or lack thereof, to the receiving environment. Consequently, this has led to the continuing poor performance and failure of on-site systems, resulting in environmental and public health consequences. As a result, there is increasing realisation that more scientifically robust evaluations in regard to site assessment and the underlying ground conditions are needed. Risk-based approaches to on-site system siting, design and management are considered the most appropriate means of improvement to the current standards and codes for on-site wastewater treatment systems. The Project Research in relation to this project was undertaken within the Gold Coast City Council region, the major focus being the semi-urban, rural residential and hinterland areas of the city that are not serviced by centralised treatment systems. The Gold Coast has over 15,000 on-site systems in use, with approximately 66% being common septic tank-subsurface dispersal systems. A recent study evaluating the performance of these systems within the Gold Coast area showed approximately 90% were not meeting the specified guidelines for effluent treatment and dispersal. The main focus of this research was to incorporate strong scientific knowledge into an integrated risk assessment process to allow suitable management practices to be set in place to mitigate the inherent risks. To achieve this, research was undertaken focusing on three main aspects involved with the performance and management of OWTS. Firstly, an investigation into the suitability of soil for providing appropriate effluent renovation was conducted. This involved detailed soil investigations, laboratory analysis and the use of multivariate statistical methods for analysing soil information. The outcomes of these investigations were developed into a framework for assessing soil suitability for effluent renovation. This formed the basis for the assessment of OWTS siting and design risks employed in the developed risk framework. Secondly, an assessment of the environmental and public health risks was performed specifically related the release of contaminants from OWTS. This involved detailed groundwater and surface water sampling and analysis to assess the current and potential risks of contamination throughout the Gold Coast region. Additionally, the assessment of public health risk incorporated the use of bacterial source tracking methods to identify the different sources of fecal contamination within monitored regions. Antibiotic resistance pattern analysis was utilised to determine the extent of human faecal contamination, with the outcomes utilised for providing a more indicative public health assessment. Finally, the outcomes of both the soil suitability assessment and ground and surface water monitoring was utilised for the development of the integrated risk framework. The research outcomes achieved through this project enabled the primary research aims and objects to be accomplished. This in turn would enable Gold Coast City Council to provide more appropriate assessment and management guidelines based on robust scientific knowledge which will ultimately ensure that the potential environmental and public health impacts resulting from on-site wastewater treatment is minimised. As part of the implementation of suitable management strategies, a critical point monitoring program (CPM) was formulated. This entailed the identification of the key critical parameters that contribute to the characterised risks at monitored locations within the study area. The CPM will allow more direct procedures to be implemented, targeting the specific hazards at sensitive areas throughout Gold Coast region.

Genetic variability and antimicrobial resistance of Ureaplasma parvum in response to maternal erythromycin treatment : a study in pregnant sheep

Background: Ureaplasmas are the most frequently isolated microorganisms from the amniotic fluid (AF) of pregnant women and can cause chronic infections that are difficult to eradicate with standard macrolide treatment. We tested the effects of erythromycin treatment on phenotypic and genotypic markers of ureaplasmal antimicrobial resistance in sheep. Method: At 50 days of gestation (d, term=145d) 12 pregnant ewes received intra-amniotic injections of U. parvum serovar 3 (erythromycin-sensitive, 2x104 colony-forming-units). At 100d ewes received: erythromycin treatment (500 mg, q3h for 4 days, IM, n=6) or no treatment (n=6). Fetuses were delivered surgically (125d) and AF and chorioamnion were collected for: culture, minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC) testing; 23S rRNA sequencing; and detection of macrolide-lincosamide-streptogramin resistance (MLSr) genes. Results: MICs of erythromycin, azithromycin and roxithromycin against AF isolates were low (range = 0.06 mg/L to 1.0 mg/L); however, chorioamnion isolates demonstrated increased resistance to roxithromycin (0.13 – 5.33 mg/L). 62.5% of chorioamnion ureaplasmas formed biofilms in vitro and mutations (125 nucleotides, 29.6%) were found in the 23S rRNA gene (domain V) of chorioamnion (but not AF) ureaplasmas. MLSr genes (ermB, msrC and msrD) were detected in 100% of chorioamnion isolates and only msrD was detected in AF isolates (40%). Conclusions: 23S rRNA mutations and MLSr genes occurred independently of erythromycin treatment, suggesting that the anatomical site of infection and microenvironment may exert selective pressures on ureaplasmas that cause genetic changes and alter antimicrobial sensitivity profiles. These results have serious implications for treatment of in utero infections.

Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment : the M77001 study group

Purpose: This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Patients and Methods: Patients were randomly assigned to six cycles of docetaxel 100 mg/m 2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression. Results: A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months. Conclusion: Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity. © 2005 by American Society of Clinical Oncology.

Control strategies to prevent total hip replacement-related infections : a systematic review and mixed treatment comparison

OBJECTIVE: To synthesise the available evidence and estimate the comparative efficacy of control strategies to prevent total hip replacement (THR)-related surgical site infections (SSIs) using a mixed treatment comparison. DESIGN: Systematic review and mixed treatment comparison. SETTING: Hospital and other healthcare settings. PARTICIPANTS: Patients undergoing THR. PRIMARY AND SECONDARY OUTCOME MEASURES: The number of THR-related SSIs occurring following the surgical operation. RESULTS: 12 studies involving 123 788 THRs and 9 infection control strategies were identified. The strategy of 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation' significantly reduced the risk of THR-related SSI compared with the referent strategy (no systemic antibiotics+plain cement+conventional ventilation), OR 0.13 (95% credible interval (CrI) 0.03-0.35), and had the highest probability (47-64%) and highest median rank of being the most effective strategy. There was some evidence to suggest that 'systemic antibiotics+antibiotic-impregnated cement+laminar airflow' could potentially increase infection risk compared with 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation', 1.96 (95% CrI 0.52-5.37). There was no high-quality evidence that antibiotic-impregnated cement without systemic antibiotic prophylaxis was effective in reducing infection compared with plain cement with systemic antibiotics, 1.28 (95% CrI 0.38-3.38). CONCLUSIONS: We found no convincing evidence in favour of the use of laminar airflow over conventional ventilation for prevention of THR-related SSIs, yet laminar airflow is costly and widely used. Antibiotic-impregnated cement without systemic antibiotics may not be effective in reducing THR-related SSIs. The combination with the highest confidence for reducing SSIs was 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation'. Our evidence synthesis underscores the need to review current guidelines based on the available evidence, and to conduct further high-quality double-blind randomised controlled trials to better inform the current clinical guidelines and practice for prevention of THR-related SSIs.

In Response: "Oral versus IV treatment for catheter-related bloodstream infections - by Burke A. Cunha"

In his letter Cunha suggests that oral antibiotic therapy is safer and less expensive than intravenous therapy via central venous catheters (CVCs) (1). The implication is that costs will fall and increased health benefits will be enjoyed resulting in a gain in efficiency within the healthcare system. CVCs are often used in critically ill patients to deliver antimicrobial therapy, but expose patients to a risk of catheter-related bloodstream infection (CRBSI). Our current knowledge about the efficiency (i.e. costeffectiveness) of allocating resources toward interventions that prevent CRBSI in patients requiring a CVC has already been reviewed (2). If for some patient groups antimicrobial therapy can be delivered orally, instead of through a CVC, then the costs and benefits of this alternate strategy should be evaluated...

An Australian native plant: A novel antimicrobial for the treatment of MRSA

Chronic wounds, often associated with venous and arterial ulcers, diabetes and pressure sores, is an area of great concern. In Australia, the cost of treating chronic wounds is conservatively estimated at $285 million/annum for the treatment of pressure ulcers and $654 million annually for the treatment and management of leg ulcers. Current figures indicate that more than seven million people suffer from chronic wounds worldwide with Australians accounting for approximately 600,000 of this number. Bacterial infection of the wound site is a major issue as contamination of a chronic wound with methicillin-resistant Staphylococcus aureus (MRSA) significantly delays wound healing. Further, once systemic, current antibiotic therapies capable of treating the infection are limited. Aboriginal bush medicine has been used for thousands of years for the treatment of wounds and sores. Hence, we selected a native Australian plant to evaluate its bactericidal activity against MRSA.

Antitumor immunity in rats against Yoshida ascites sarcoma after treatment with antibiotics

Chromomycin A3, mithramycin, olivomycin and actinomycin D, four antitumor antibiotics inhibit growth of Yoshida ascites sarcoma (YAS). The antibiotic treated tumor-free rats exhibit antitumor immunity as judged by rejection of subsequent tumor transplant. The lymphocytes from immune rats are able to inhibit tumor growth in syngenic animals.

What consumers think, do and say about antibiotic use

Objective The objectives of this study were to investigate (1) the attitudes and behaviours of Australian consumers in antibiotic use, and (2) their understanding of antibiotic resistance. Methods Semi-structured interviews were conducted with consumers in May/June 2015. Convenience sampling was used to recruit consumers between 18–54 years old. Thirty-two consumers were interviewed. Transcripts were analysed to identify themes. Lessons Learned Dominant themes for attitudes and behaviours regarding antibiotics were (a) avoidance of antibiotic use unless clinically warranted; (b) antibiotics were useful but “weakened the body”; and (c) use of complementary medicines as adjuncts to antibiotics or to strengthen the immune system. Key information needs were (a) unambiguous instructions from GPs when prescribed antibiotics, to avoid inappropriate medicine-taking behaviour; (b) rationale for antibiotic selection; and (c) treatment duration. Antibiotic resistance was conceptualised in three ways: as a property of the body (body becomes resistant to antibiotics); the medication (antibiotic no longer effective); and the bacteria (bacteria is resistant). Antibiotic resistance was perceived as an issue that would only affect the wider community in the future, although most recognised that it is a current challenge for hospitals. Personal good health and/or avoidance of antibiotics were perceived as insurance against being adversely affected by antibiotic resistance. Implications A structured survey (discrete choice experiment) will be developed from these findings to investigate how consumers trade-off on factors influencing antibiotic use. Public health campaigns promoting conservation of antibiotics can benefit from these findings.

Helicobacter pylori: resistance and treatment results in Finland

Background: Helicobacter pylori infection is usually acquired in early childhood and is rarely resolved spontaneously. Eradication therapy is currently recommended virtually to all patients. While the first and second therapies are prescribed without knowing the antibiotic resistance of the bacteria, it is important to know the primary resistance in the population. Aim: This study evaluates the primary resistance of H. pylori among patients in primary health care throughout Finland, the efficacy of three eradication regimens, the symptomatic response to successful therapy, and the effect of smoking on gastric histology and humoral response in H. pylori-positive patients. Patients and methods: A total of 23 endoscopy referral centres located throughout Finland recruited 342 adult patients with positive rapid urease test results, who were referred to upper gastrointestinal endoscopy from primary health care. Gastric histology, H. pylori resistance and H. pylori serology were evaluated. The patients were randomized to receive a seven-day regimen, comprising 1) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and metronidazole 400 mg t.d. (LAM), 2) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (LAC) or 3) ranitidine bismuth citrate 400 mg b.d., metronidazole 400 mg t.d. and tetracycline 500 mg q.d. (RMT). The eradication results were assessed, using the 13C-urea breath test 4 weeks after therapy. The patients completed a symptom questionnaire before and a year after the therapy. Results: Primary resistance of H. pylori to metronidazole was 48% among women and 25% among men. In women, metronidazole resistance correlated with previous use of antibiotics for gynaecologic infections and alcohol consumption. Resistance rate to clarithromycin was only 2%. Intention-to-treat cure rates of LAM, LAC, and RMT were 78%, 91% and 81%. While in metronidazole-sensitive cases the cure rates with LAM, LAC and RMT were similar, in metronidazole resistance LAM and RMT were inferior to LAC (53%, 67% and 84%). Previous antibiotic therapies reduced the efficacy of LAC, to the level of RMT. Dyspeptic symptoms in the Gastrointestinal Symptoms Rating Scale (GSRS) were decreased by 30.5%. In logistic regression analysis, duodenal ulcer, gastric antral neutrophilic inflammation and age from 50 to 59 years independently predicted greater decrease in dyspeptic symptoms. In the gastric body, smokers had milder inflammation and less atrophy and in the antrum denser H. pylori load. Smokers also had lower IgG antibody titres against H. pylori and a smaller proportional decrease in antibodies after successful eradication. Smoking tripled the risk of duodenal ulcers. Conclusions: in Finland H. pylori resistance to clarithromycin is low, but metronidazole resistance among women is high making metronidazole-based therapies unfavourable. Thus, LAC is the best choice for first-line eradication therapy. The effect of eradication on dyspeptic symptoms was only modest. Smoking slows the progression of atrophy in the gastric body.

Lipid coated mesoporous silica nanoparticles as an oral delivery system for targeting and treatment of intravacuolar Salmonella infections

Lipid coated mesoporous silica nanoparticle (L-MSN) were synthesized for oral delivery of ciprofloxacin for intracellular elimination of Salmonella pathogen. The particle size was found to be between 50-100 nm with a lipid coat of approximately 5 nm thickness. The lipid coating was achieved by sonication of liposomes with the MSN particles and evaluated by CLSMand FTIR studies. The L-MSN particles exhibited lower cytotoxicity compared to bare MSN particles. Ciprofloxacin, a fluoroquinolone antibiotic, loaded into the L-MSN particles showed enhanced antibacterial activity against free drug in in vitro assays. The lipid coat was found to aid in intravacuolar targeting of the drug cargo as observed by confocal microscopy studies. We also observed that a lower dose of antibiotic was sufficient to clear the pathogen from mice and increase their survivability using the L-MSN oral delivery system.