Antibiotic Treatment Regimens Research Articles

Cumplimiento de las guías de la Sociedad Europea de Cardiología y morbimortalidad por endocarditis infecciosa

ObjectiveThe antibiotic treatment recommended for infectious endocarditis (IE) has a low level of evidence. Our objective was to determine whether compliance with the recommendations of the European Society of Cardiology (ESC) was related to lower inhospital morbidity and mortality for this disease. MethodsA retrospective study was conducted on 162 cases of IE diagnosed between 2005 and 2014. A propensity score-matching analysis was performed to determine the effect of treatment on hospital mortality. ResultsThere were no differences in terms of disease complications between the treatment groups. Hospital mortality was 29.2% when the treatment was adjusted to the guidelines and 28.2% when the treatment was not adjusted (OR=1.048; 95%CI: 0.442-2.484; P=.916). ConclusionThe use of the ESC guidelines does not appear to translate into a reduction in hospital morbidity and mortality due to IE when compared with alternative antibiotic treatment regimens.

009.1 Standardised, quality assured time-kill curve analysis and pharmacodynamic functions of different antibiotics forin vitroevaluation of treatment regimens forneisseria gonorrhoeae

Introduction Neisseria gonorrhoeae shows increasing resistance to first line empirical treatment, which demonstrates the need for robust methods to evaluate antibiotic treatment regimens. Antibiotic efficacy is traditionally determined in vitro by measuring minimum inhibitory concentrations (MICs). Time-kill curve assays for N. gonorrhoeae have been difficult to standardise. We developed a new time-kill curve assay and used pharmacodynamics functions to analyse the relationship between antibiotic concentration and bacterial net growth rate. Methods We used a defined medium (Graver-Wade medium) and grew bacteria in 96-well microtiter plates. To measure colony forming units over a time course of six hours, we used a previously described drop plate method and spotted 10 µl droplets on chocolate agar with a multichannel pipette. The assay was validated using 16 reference strains, representing diffent clades of the N. gonorrhoeae phylogenetic tree. We then studied a highly sensitive strain isolated in 1954 in Denmark in detail. Penicillin G, spectinomycin, gentamicin, tetracyline, chloramphenicol, ciprofloxacin, azithromycin, cefixime and ceftriaxone were examined in concentrations from 0.016× to 16×MIC. A pharmacodynamic function was fitted to the net bacterial growth rates at each concentration, resulting in four parameters that describe the pharmacodynamic properties of each antibiotic. Results Our time-kill curve assay was reproducible for all the N. gonorrhoeae strains tested. Ciprofloxacin and spectinomycin induced the strongest bactericidal effect during the first six hours. Tetracycline and chloramphenicol were the only antibiotics that showed a purely bacteriostatic effect. Differences in the shape of the pharmacodynamic functions illustrate the time and concentration dependent properties of the antibiotics. Conclusion We developed a standardised, robust and quality-assured time-kill curve assay for N. gonorrhoeae . Pharmacodynamic functions allowed classification of nine antibiotics according to their antimicrobial properties. These methods can be used to investigate new antibiotic regimens and help to improve dosing strategies. Disclosure of interest statement This work was supported by SystemsX, Switzerland, Orebro County Council Research Committee and the Foundation for Medical Research at Orebro University Hospital, Sweden.

Treatment of bacterial skin infections in ED observation units: factors influencing prescribing practice

ObjectiveThe Infectious Disease Society of America (IDSA) publishes evidence-based guidelines for the treatment of skin and soft tissue infections. How closely physicians follow these guidelines is unknown, particularly in the emergency department observation unit (EDOU) where increasing numbers of patients are treatment for these infections. Our objectives were to describe (1) the antibiotic treatment patterns EDOU patients, (2) physicians' adherence to the IDSA guidelines, and (3) factors that influence physician's prescribing practices. MethodsThis prospective cohort enrolled adult patients discharged from an EDOU at an academic medical center after treatment for a skin or soft tissue infection. Information was collected from chart review and patient interview pertaining to the patient's sociodemographic characteristics, presenting illness, and antibiotic treatment regimens. Treatment regimens were compared with national guidelines. ResultsThe study included 193 patients of which only 43% were treated according to IDSA guidelines, 42% were overtreated, and 15% were undertreated. Women were more likely to be undertreated (relative risk, 1.58; 95% confidence interval, 1.21-2.06), whereas patients 50 years and older were at risk for overtreatment (relative risk, 1.44; 95% confidence interval, 1.03-2.02). Women also received shorter courses of antibiotic therapy with an average of 9.6 days of treatment compared with 10.6 days for men. ConclusionsPhysician antibiotic prescribing practices demonstrated poor adherence to IDSA guidelines and were influenced by the patient's age and sex. Standardized antibiotic protocols for treatment of skin and soft tissue infections to IDSA guidelines in the EDOU would minimize physician bias.

Efficacy of the antimicrobial peptide TP4 against Helicobacter pylori infection: in vitro membrane perturbation via micellization and in vivo suppression of host immune responses in a mouse model.

Helicobacter pylori infection is marked by a strong association with various gastric diseases, including gastritis, ulcers, and gastric cancer. Antibiotic treatment regimens have low success rates due to the rapid occurrence of resistant H. pylori strains, necessitating the development of novel anti-H. pylori strategies. Here, we investigated the therapeutic potential of a novel peptide, Tilapia Piscidin 4 (TP4), against multidrug resistant gastric pathogen H. pylori, based on its in vitro and in vivo efficacy.TP4 inhibited the growth of both antibiotic-sensitive and -resistant H. pylori (CagA+, VacA+) via membrane micelle formation, which led to membrane depolarization and extravasation of cellular constituents. During colonization of gastric tissue, H. pylori infection maintains high T regulatory subsets and a low Th17/Treg ratio, and results in expression of both pro- and anti-inflammatory cytokines. Treatment with TP4 suppressed Treg subset populations and pro- and anti- inflammatory cytokines. TP4 restored the Th17/Treg balance, which resulted in early clearance of H. pylori density and recovery of gastric morphology. Toxicity studies demonstrated that TP4 treatment has no adverse effects in mice or rabbits. The results of this study indicate that TP4 may be an effective and safe monotherapeutic agent for the treatment of multidrug resistant H. pylori infections.

Electrochemical Sensors for Continuous Monitoring of Bacterial Infections

The Infectious Diseases Society of America recently named six pathogens as the greatest threat to modern day medicine as they currently account for over two thirds of all hospital acquired infections and have the ability to rapidly develop antibiotic resistance. While pharmaceutical companies work to develop new antimicrobial compounds to treat infections, one of the best ways to prevent the emergence of antibiotic resistance, and improve patient outcomes, is early detection followed by fast identification and treatment with targeted antibiotics. To this end, we are developing electrochemical sensors that will be able to continuously monitor patient wounds for signs of infection. Our detection mechanism uses virulence factors that are excreted by pathogens into their local environment. One such approach measures production of pyocyanin by Pseudomonas aeruginosa, a quorum-sensing molecule that is unique to this species and linked to biofilm formation. As pyocyanin is redox-active, it can be detected electrochemically using standard techniques such as square wave voltammetry (SWV), where the sensitivity of the measurements is limited by the concentration of pyocyanin present in the sample. Since demonstrating the initial concept, we have focused on improving the sensing system and developing new applications for it within healthcare settings. Here, we will present our recent findings for how it may be possible to improve the sensitivity of the system by coating the electrodes with compounds that cause cells to up-regulate the production of pyocyanin. We have also investigated whether pyocyanin production rates are affected by antibiotic treatment. We will show that a simple electrochemical sensor can be used to provide quantitative information about the efficacy of antibiotic treatment regimes for P. aeruginosa infections. We measured the concentration of pyocyanin surrounding biofilms of P. aeruginosa cells while exposing them to a range of antibiotic concentrations. Figure 1 shows SWVs of Escherichia coli and P. aeruginosa biofilms grown in trypticase soy broth (TSB) for A) 0 hr, B) 12 hr, then exposed to flowing 100 mg/L colistin sulfate TSB after approximately C) 22 hr, D) 35 hr, E) 40 hr, and F) 45 hr. The baseline current for the blank TSB was subtracted from the data shown. SWV performed from -0.5 to 0.2 volts at a frequency of 15 Hz and an amplitude voltage of 50 mV. The E. coli cells do not produce pyocyanin and, therefore, no peak is seen in the current around -0.25 volts. The results show that pyocyanin concentration decreases as cells in the biofilm are killed, and therefore can be used to monitor the effectiveness of treatment. This work was supported by the U.S. National Science Foundation under Grant #1125535. Figure 1

Safety and efficacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trial.

Severe infections remain one of the main causes of neonatal deaths worldwide. Possible severe infection is diagnosed in young infants (aged 0-59 days) according to the presence of one or more clinical signs. The recommended treatment is hospital admission with 7-10 days of injectable antibiotic therapy. In low-income and middle-income countries, barriers to hospital care lead to delayed, inadequate, or no treatment for many young infants. We aimed to identify effective alternative antibiotic regimens to expand treatment options for situations where hospital admission is not possible. We did this randomised, open-label, equivalence trial in four urban hospitals and one rural field site in Bangladesh to determine whether two alternative antibiotic regimens with reduced numbers of injectable antibiotics combined with oral antibiotics had similar efficacy and safety to the standard regimen, which was also used as outpatient treatment. We randomly assigned infants who showed at least one clinical sign of severe, but not critical, infection (except fast breathing alone), whose parents refused hospital admission, to one of the three treatment regimens. We stratified randomisation by study site and age (<7 days or 7-59 days) using computer-generated randomisation sequences. The standard treatment was intramuscular procaine benzylpenicillin and gentamicin once per day for 7 days (group A). The alternative regimens were intramuscular gentamicin once per day and oral amoxicillin twice per day for 7 days (group B) or intramuscular procaine benzylpenicillin and gentamicin once per day for 2 days, then oral amoxicillin twice per day for 5 days (group C). The primary outcome was treatment failure within 7 days after enrolment. Assessors of treatment failure were masked to treatment allocation. Primary analysis was per protocol. We used a prespecified similarity margin of 5% to assess equivalence between regimens. This study is registered with ClinicalTrials.gov, number NCT00844337. Between July 1, 2009, and June 30, 2013, we recruited 2490 young infants into the trial. We assigned 830 infants to group A, 831 infants to group B, and 829 infants to group C. 2367 (95%) infants fulfilled per-protocol criteria. 78 (10%) of 795 per-protocol infants had treatment failure in group A compared with 65 (8%) of 782 infants in group B (risk difference -1.5%, 95% CI -4.3 to 1.3) and 64 (8%) of 790 infants in group C (-1.7%, -4.5 to 1.1). In group A, 14 (2%) infants died before day 15, compared with 12 (2%) infants in group B and 12 (2%) infants in group C. Non-fatal relapse rates were similar in all three groups (12 [2%] infants in group A vs 13 [2%] infants in group B and 10 [1%] infants in group C). Our results suggest that the two alternative antibiotic regimens for outpatient treatment of clinical signs of severe infection in young infants whose parents refused hospital admission are as efficacious as the standard regimen. This finding could increase treatment options in resource-poor settings when referral care is not available or acceptable.

Risk of Clostridium difficile infection in intensive care unit patients with sepsis exposed to metronidazole

Background: Antimicrobial agents used to treat Clostridium difficile infection (CDI), such as metronidazole and vancomycin, have been used during antibiotic treatment of other infections to try to prevent the development of CDI. We evaluated the hypothesis that intensive care unit (ICU) patients who receive metronidazole as part of an antibiotic treatment regimen for sepsis have a lower risk of subsequently developing CDI. Methods: This was a nested case-control study in a cohort of ICU patients who received antibiotic therapy for sepsis. Results: A total of 10 012 patients aged ≥ 18 years were admitted to the Cooper University Hospital medical/surgical ICU from 1/1/2003 to 12/31/2008. After applying inclusion criteria including having received antibiotic therapy for sepsis and subsequently having developed CDI, 67 cases were identified. The cases were matched for age, gender, date of ICU admission, and hospital length of stay to 67 controls that also received antibiotic therapy for sepsis but did not subsequently develop CDI. In the multivariate analysis, there was no association between metronidazole exposure and the risk of CDI (odds ratio (OR) = 0.57; p = 0.23). The only significant associations on multivariate analysis were antifungal therapy (OR = 0.30; p = 0.02) and aminoglycoside and/or colistin therapy (OR = 0.17; p = 0.02). Conclusions: No association was found between metronidazole use and subsequent CDI in ICU patients who received antibiotic therapy for sepsis.

Antibiotic regimens for treatment of infections due to multidrug-resistant Gram-negative pathogens: An evidence-based literature review.

Evidences regarding the efficacy of different antibiotic regimens proposed for treatment of multidrug-resistant (MDR) Gram-negative pathogens have been reviewed. Available data in Scopus, Medline, EMBASE, the Cochrane central register of controlled trials, and Cochrane database of systematic reviews have been collected. Several antibiotic regimens are proposed for treatment of MDR Gram-negative infections (defined as nonsusceptibility to at least one agent in three or more antimicrobial categories). The most challenging issue is the treatment of carbapenem-resistant (CR) Gram-negative pathogens. A carbapenem plus either colistin or tigecycline was the most effective regimen for treatment of CR Gram-negative pathogens with low-level resistance (minimal inhibitory concentration [MIC] ≤ 8 mg/L). However, in high-level resistance (MIC > 8 mg/L), combination of colistin and tigecycline showed promising effect.

Update on hidradenitis suppurativa: connecting the tracts.

Hidradenitis suppurativa (HS) is a debilitating skin disease characterized by recurrent abscesses, sinus tract formation, and scarring. Prevalence estimates range from 0.053% to 4.1%, although HS is likely an underdiagnosed disease. Although the first reports of HS date back to the mid-19th century, the disease continues to plague patients and physicians desperate for a definitive treatment. Advances in the understanding of the disease process include the possibility of a defective basement membrane at the sebofollicular junction of the folliculopilosebaceous unit (FPSU; that is, where the sebaceous gland empties into the hair follicle) as an initiating event followed by secondary bacterial colonization. New evidence suggests that bacteria living in a community, known as a biofilm, rather than single planktonic bacteria in HS lesions may explain why HS can be resistant to current antibiotic treatment regimens. Available treatment options have expanded to include triple-antibiotic therapy, tumor necrosis factor (TNF-α) and interleukin-1 (IL-1) inhibitors (biologics), laser therapy, and surgical excision, including the skin tissue-sparing excision with electrosurgical peeling procedure. Despite the array of treatments available, many patients continue to struggle with the embarrassment, pain, odor, and frustration that accompany this often isolating disease. Physicians should address comorbidities in HS, including the psychosocial issues patients with HS frequently encounter. Patients can be directed to HS support groups, where they can openly discuss their frustrations, share their experiences in dealing with HS, and band together to advocate for themselves. HS is misunderstood by both patients and physicians, often resulting in a delay in clinical presentation and diagnosis. Patients and physicians across multiple specialties must work together to expand awareness of and interest in HS, so that one day, individuals with HS can be freed from this crippling disease.

Prevalence of PUFA Rich Thraustochytrids sps. along the Coast of Mumbai for Production of Bio Oil

Aims: To obtain axenic cultures of Thraustochytrids and assess the diversity of Thraustochytrids spps within the mangrove regions of Mumbai for their ability to produce DHA. Methods and Results: Samples obtained from various mangrove regions in and around the Mumbai coastline were screened for presence of Thraustochytrids cultures. Modified procedures involving use of various media and antibiotic treatment regimes were formulated to obtain axenic cultures of Thraustochytrids. Though 40% of the samples under study showed presence of pollen baitable Thraustochytrids, only 5% of these spps could be recovered through direct isolation techniques on the conventional penicillin streptomycin B1 agar plate. In contrast, use of antibiotic cocktail during baiting lead to better recovery such that 57.14% of all the positive pollen baited samples were able to be recovered as axenic isolates on isolation on antibiotic laden B1 agar. For most of the isolates the fatty acid profile range between 60 to 76% of their dry cell mass; with total fatty acid content of 5.92±0.41 g L-1 of which 1.97±0.08 g L-1 was DHA. Conclusion: Though marine mangrove environments are known habitat of Thraustochytrids its axenic cultivation is a challenge especially as the profile of contaminating bacteria and fungi within polluted areas varies from that within pristine locales. Removal of bacteria and fungi from an environment loaded with an higher organic load required mixture of three antibiotics and one antifungal; rifampicin (300 mg l-1), streptomycin/penicillin (25 mg l-1) and nystatin (10 mg l-1) to be incorporated in seawater samples for a minimum of 2 days so that Thraustochytrids could be selectively isolated from the Indian Mangrove region,. Significance and Impact of Study: This data represents the first extensive study on the prevalence of Thraustochytrids across the coast of Mumbai and the combination of antibiotics that need to be used for its effective recovery.

PO-0571 Pathogens And Empiric Treatment Of Sepsis In A Neonatal Intensive Care Unit

<h3>Background and aims</h3> Sepsis is a major cause of morbidity and mortality in newborns. We aimed to assess the efficacy of the current empiric regimens commonly used in neonatal intensive care units (NICU) and to describe the characteristics of newborns with sepsis. <h3>Methods</h3> Infants admitted to the NICU with a sepsis diagnosis during January 2012 and December 2013 were assessed in a retrospective manner. While infants with early onset neonatal sepsis (EO-NS) diagnosis had received an empiric regimen including ampicillin and gentamicin, those with a late onset neonatal sepsis (LO-NS) diagnosis received carbapenem, vancomycin and fluconazole. Culture antibiogram results were compared with empirical treatment choices. Mortality and recovery rates with empiric treatment was documented. We used the MedCalc statistical software for statistical analysis. <h3>Results</h3> We identified 124 infants (66 males and 58 females). Of these 43 (34.7%) were diagnosed with EO-NS and 81 (65.3%) with LO-NS. While the rate of positive blood culture results was 36% in the EO-NS group it was 84% in the LO-NS group. Treatment success rates were 93,5% in the EO-NS group, and 81,7% in the LO-NS group. Carbapenem resistance was identified in 10,5% of the newborns in the LO-NS group. Mortality rates were 4.6% in the EO-NS and 8,9% in the LO-NS group. <h3>Conclusions</h3> The success rates of empiric antibiotic treatment was high in both the EO-NS and LO-NS group. The microbial flora of the NICU should be taken into account when deciding for the empirical antibiotic treatment regimens in infants with hospital acquired sepsis.

Evaluation of a Once-Daily Vancomycin Regimen in an Outpatient Leukemia/Bone Marrow Transplant Clinic (OD-VANCO Study).

The Leukemia/Bone Marrow Transplant Program of British Columbia manages patients with high-risk febrile neutropenia and those with non-neutropenic immunocompromised states in an outpatient clinic setting. Because the program treats outpatients only, once-daily administration of IV antibiotics is desirable. A high-dose, once-daily vancomycin nomogram was developed and implemented as part of the antibiotic treatment regimen. To determine if therapeutic vancomycin trough levels could be achieved with a high-dose, once-daily regimen in this outpatient setting. A prospective, single-centre, observational cohort study was conducted over a 7-month period. Outpatients in the Leukemia/Bone Marrow Transplant Program were started on IV vancomycin with the high-dose, once-daily vancomycin nomogram, and outcomes were assessed. Of 48 outpatients treated over the 7-month period, 10 (21%) had therapeutic vancomycin trough concentrations (i.e., greater than 10 mg/L). Thirty-five (90%) of the 39 patients with suspected clinical infection experienced clinical cure, and 6 (67%) of the 9 patients with documented microbiological infection experienced microbiological cure. Thirty (62%) of the 48 patients experienced symptoms of "red man syndrome", and 7 (15%) experienced some degree of nephrotoxicity. Two of 3 patients with laboratory-reported minimum inhibitory concentration (MIC) for identified pathogens had a calculated area under the curve to MIC ratio greater than or equal to 400. The high-dose, once-daily vancomycin nomogram was effective in attaining trough levels greater than 10 mg/L in only 21% of patients in this study. A substantial number of adverse drug reactions were observed. Given these results, high-dose, once-daily vancomycin is no longer recommended for outpatient therapy.

Prosthetic joint infection: managing infection in a bionic era.

There is increasing demand for prosthetic joint surgery and patients are becoming more challenging due to an ageing population often with comorbidities and immunosuppression. While prosthetic joint infection (PJI) rates are generally low, infection can be catastrophic for the patient and hence prevention of infection is critical. Infection, when it does occur, is further complicated by the global rise in antimicrobial resistance. This article introduces a series of papers on the epidemiology of PJI, its diagnosis, use of novel inflammatory markers and molecular techniques, clinical presentation, importance of biofilms, treatment guidelines and, finally, various strategies and novel antibiotic treatment regimens.

Propionibacterium acnes: from commensal to opportunistic biofilm-associated implant pathogen.

Propionibacterium acnes is known primarily as a skin commensal. However, it can present as an opportunistic pathogen via bacterial seeding to cause invasive infections such as implant-associated infections. These infections have gained more attention due to improved diagnostic procedures, such as sonication of explanted foreign materials and prolonged cultivation time of up to 14 days for periprosthetic biopsy specimens, and improved molecular methods, such as broad-range 16S rRNA gene PCR. Implant-associated infections caused by P. acnes are most often described for shoulder prosthetic joint infections as well as cerebrovascular shunt infections, fibrosis of breast implants, and infections of cardiovascular devices. P. acnes causes disease through a number of virulence factors, such as biofilm formation. P. acnes is highly susceptible to a wide range of antibiotics, including beta-lactams, quinolones, clindamycin, and rifampin, although resistance to clindamycin is increasing. Treatment requires a combination of surgery and a prolonged antibiotic treatment regimen to successfully eliminate the remaining bacteria. Most authors suggest a course of 3 to 6 months of antibiotic treatment, including 2 to 6 weeks of intravenous treatment with a beta-lactam. While recently reported data showed a good efficacy of rifampin against P. acnes biofilms, prospective, randomized, controlled studies are needed to confirm evidence for combination treatment with rifampin, as has been performed for staphylococcal implant-associated infections.

Harnwegsinfektionen

Urinary tract infections (UTI) are amongst the most frequent bacterial infections and therefore responsible for a great amount of antibiotic administration. UTI may present as benign, uncomplicated cystitis or severe, life-threatening urosepsis. Due to the heterogeneity of UTI the European Section of Infections in Urology (ESIU) has introduced a phenotypical classification, based upon the clinical presentation, the risk factors and the antibiotic susceptibility of the causative pathogens. Antibiotic treatment of the UTI varies accordingly. In uncomplicated cystitis antibiotics with low potential for collateral damage are recommended, which are mainly indicated for these infections. In uncomplicated pyelonephritis fluoroquinolones and 3rd generation cephalosporines are recommended. Antibiotic treatment regimens of complicated UTI depend very much on the antibiotic susceptibility according to regional resistance statistics. In urosepsis an early diagnosis and therapy is mandatory. In this regard a procalcitonin level > 0.25 µg/l has a good sensitivity and acceptable specificity in predicting bacteremia. Apart from the early antibiotic therapy successful decompression of the obstructed urinary tract is a predictor of survival. In children UTI are also amongst the most important bacterial infections, although symptoms are frequently not characteristic. The correct sampling of urine for microbiological investigations is critical. Due to the increasing fluoroquinolone resistance, infectious complications after transrectal prostate biopsy are becoming more frequent. Strategies to decrease complications encompass, amongst others, microbiological screening of the faecal flora for fluoroquinolone resistance, administration of alternative antibiotics for prophylaxis and alternative techniques for biopsy, such as perineal prostate biopsy.

Antibiotic Treatment and Timing of Reimplantation

PJI is traditionally treated with intravenous (IV) antibiotics in order to obtain the minimum inhibitory concentration in the shortest time possible. Once this goal is met and there is clinical evidence of improvement, some IV antibiotic regimens can be switched to oral regimens. There is scarce literature reporting on the use of oral (combined or single) antibiotic therapy for the treatment of PJIs without an initial IV regimen [1–5]. Most of these studies were conducted in cases where the prosthesis was retained. There is one study in which no oral or prolonged IV regimen was used after debridement and the use of an antibiotic-impregnated cement spacers led to a 87% eradication rate [6]. No literature conclusively supports the use of only oral (combined or single) antibiotic therapy prior to reimplantation. The recently-published guidelines of the Infectious Diseases Society of America (IDSA) [7] suggest that pathogen-specific, highly bioavailable oral therapy (e.g. linezolid or fluoroquinolones) may be an alternative as initial therapy for some cases of PJI. Concerns against the routine use of appropriate oral agents in the treatment of PJI largely comprise questions of patient medication compliance and the long-term use of medication therapy with less intensive efficacy and toxicity monitoring.

Antibiotic Resistance in Human Chronic Periodontitis Microbiota

Patients with chronic periodontitis (CP) may yield multiple species of putative periodontal bacterial pathogens that vary in their antibiotic drug susceptibility. This study determines the occurrence of in vitro antibiotic resistance among selected subgingival periodontal pathogens in patients with CP. Subgingival biofilm specimens from inflamed deep periodontal pockets were removed before treatment from 400 adults with CP in the United States. The samples were cultured, and selected periodontal pathogens were tested in vitro for susceptibility to amoxicillin at 8 mg/L, clindamycin at 4 mg/L, doxycycline at 4 mg/L, and metronidazole at 16 mg/L, with a post hoc combination of data for amoxicillin and metronidazole. Gram-negative enteric rods/pseudomonads were subjected to ciprofloxacin disk-diffusion testing. Overall, 74.2% of the patients with CP revealed subgingival periodontal pathogens resistant to at least one of the test antibiotics. One or more test species, most often Prevotella intermedia/nigrescens, Streptococcus constellatus, or Aggregatibacter actinomycetemcomitans, were resistant in vitro to doxycycline, amoxicillin, metronidazole, or clindamycin, in 55%, 43.3%, 30.3%, and 26.5% of the patients with CP, respectively. Fifteen percent of patients harbored subgingival periodontal pathogens resistant to both amoxicillin and metronidazole, which were mostly either S. constellatus (45 individuals) or ciprofloxacin-susceptible strains of Gram-negative enteric rods/pseudomonads (nine individuals). Patients with CP in the United States frequently yielded subgingival periodontal pathogens resistant in vitro to therapeutic concentrations of antibiotics commonly used in clinical periodontal practice. The wide variability found in periodontal pathogen antibiotic-resistance patterns should concern clinicians empirically selecting antibiotic treatment regimens for patients with CP.

Microbiota and Metabolite Profiling Reveal Specific Alterations in Bacterial Community Structure and Environment in the Cystic Fibrosis Airway during Exacerbation

Chronic polymicrobial infections of the lung are the foremost cause of morbidity and mortality in cystic fibrosis (CF) patients. The composition of the microbial flora of the airway alters considerably during infection, particularly during patient exacerbation. An understanding of which organisms are growing, their environment and their behaviour in the airway is of importance for designing antibiotic treatment regimes and for patient prognosis. To this end, we have analysed sputum samples taken from separate cohorts of CF and non-CF subjects for metabolites and in parallel, and we have examined both isolated DNA and RNA for the presence of 16S rRNA genes and transcripts by high-throughput sequencing of amplicon or cDNA libraries. This analysis revealed that although the population size of all dominant orders of bacteria as measured by DNA- and RNA- based methods are similar, greater discrepancies are seen with less prevalent organisms, some of which we associated with CF for the first time. Additionally, we identified a strong relationship between the abundance of specific anaerobes and fluctuations in several metabolites including lactate and putrescine during patient exacerbation. This study has hence identified organisms whose occurrence within the CF microbiome has been hitherto unreported and has revealed potential metabolic biomarkers for exacerbation.

Development of antibiotic regimens using graph based evolutionary algorithms

This paper examines the use of evolutionary algorithms in the development of antibiotic regimens given to production animals. A model is constructed that combines the lifespan of the animal and the bacteria living in the animal's gastro-intestinal tract from the early finishing stage until the animal reaches market weight. This model is used as the fitness evaluation for a set of graph based evolutionary algorithms to assess the impact of diversity control on the evolving antibiotic regimens. The graph based evolutionary algorithms have two objectives: to find an antibiotic treatment regimen that maintains the weight gain and health benefits of antibiotic use and to reduce the risk of spreading antibiotic resistant bacteria. This study examines different regimens of tylosin phosphate use on bacteria populations divided into Gram positive and Gram negative types, with a focus on Campylobacter spp. Treatment regimens were found that provided decreased antibiotic resistance relative to conventional methods while providing nearly the same benefits as conventional antibiotic regimes. By using a graph to control the information flow in the evolutionary algorithm, a variety of solutions along the Pareto front can be found automatically for this and other multi-objective problems.

Antibiotics for treating chronic osteomyelitis in adults.

Chronic osteomyelitis is generally treated with antibiotics and surgical debridement but can persist intermittently for years with frequent therapeutic failure or relapse. Despite advances in both antibiotic and surgical treatment, the long-term recurrence rate remains around 20%. This is an update of a Cochrane review first published in 2009. To determine the effects of different systemic antibiotic treatment regimens for treating chronic osteomyelitis in adults. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (October 2012), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2012, Issue 9), MEDLINE (January 1948 to September Week 4 2012), EMBASE (January 1980 to 2012 Week 40), LILACS (October 2012), the WHO International Clinical Trials Registry Platform (June 2012) and reference lists of relevant articles. Randomised controlled trials (RCTs) or quasi-RCTs addressing the effects of different antibiotic treatments given after surgical debridement for chronic osteomyelitis in adults. Two review authors independently screened papers for inclusion, extracted data and appraised risk of bias in the included trials. Where appropriate, we pooled data using the fixed-effect model. We included eight small trials involving a total of 282 participants with chronic osteomyelitis. Data were available from 248 participants. Most participants were male with post-traumatic osteomyelitis, usually affecting the tibia and femur, where recorded. The antibiotic regimens, duration of treatment and follow-up varied between trials. All trials mentioned surgical debridement before starting on antibiotic therapy as part of treatment, but it was unclear in four trials whether all participants underwent surgical debridement.We found that study quality and reporting were often inadequate. In particular, we judged almost all trials to be at moderate to high risk of bias due to failure to conceal allocation and inadequate follow-up.Four trials compared oral versus parenteral route for administration of antibiotics. There was no statistically significant difference between the two groups in the remission at the end of treatment (70/80 versus 58/70; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.92 to 1.18; four trials, 150 participants). There was no statistically significant difference between the two groups in the remission rate 12 or more months after treatment (49/64 versus 44/54; RR 0.94, 95% CI 0.78 to 1.13; three trials, 118 participants). There was also no significant difference between the two groups in the occurrence of mild adverse events (11/64 versus 8/54; RR 1.08, 95% CI 0.49 to 2.42; three trials, 118 participants) or moderate and severe adverse events (3/49 versus 4/42; RR 0.69, 95% CI 0.19 to 2.57; three trials, 91 participants). Superinfection occurred in participants of both groups (5/66 in the oral group versus 4/58 in the parenteral group; RR 1.08, 95% CI 0.33 to 3.60; three trials, 124 participants).Single trials with few participants found no statistical significant differences for remission or adverse events for the following four comparisons: oral only versus parenteral plus oral administration; parenteral plus oral versus parenteral only administration; two different parenteral antibiotic regimens; and two different oral antibiotic regimens. No trials compared different durations of antibiotic treatment for chronic osteomyelitis, or adjusted the remission rate for bacteria species or severity of disease. Limited and low quality evidence suggests that the route of antibiotic administration (oral versus parenteral) does not affect the rate of disease remission if the bacteria are susceptible to the antibiotic used. However, this and the lack of statistically significant differences in adverse effects need confirmation. No or insufficient evidence exists for other aspects of antibiotic therapy for chronic osteomyelitis.The majority of the included trials were conducted over 20 years ago and currently we are faced with a far higher prevalence of bacteria that are resistant to many of the available antibiotics used for healthcare. This continuously evolving bacterial resistance represents another challenge in the choice of antibiotics for treating chronic osteomyelitis.