Long-term Antibiotic Research Articles

Anti-inflammatory and antimicrobial activity of bioactive hydroxyapatite/silver nanocomposites

Biomaterials are often used in orthopedic surgery like cavity fillings. However, related complications often require long-term systemic antibiotics, device removal, and extended rehabilitation. Hydroxyapatite/silver (HA/Ag) composites have been proposed as implantation biomaterials owing to the osteogenic properties of hydroxyapatite and to the antimicrobial efficiency of silver. Nevertheless, higher silver concentrations induce cytotoxic effects. The aim of this study was to synthesize and characterize HA/Ag nanocomposites that will allow us to use lower concentrations of silver nanoparticles with better antimicrobial efficiency and anti-inflammatory properties. The characterization of HA/Ag was performed by scanning electron microscopy, energy dispersive spectroscopy, X-ray diffraction, Fourier-transform infrared spectra, X-ray photoelectron spectroscopy, and laser diffraction. Bioactivity was evaluated under a simulated body fluid. The viability of osteoblast like-cells (MG-63) was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) and the antimicrobial activity was evaluated by the standard McFarland method. The detection of nitric oxide was measured by a colorimetric assay and the inflammatory cytokines by flow cytometry. We obtained particulate composites of calcium phosphates identified as hydroxyapatite and silver nanoparticles. The bioactivity of the HA/Ag nanocomposites on SFB was confirmed by apatite formations. The viability of MG-63 cells was not affected. We also found antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans owing to the presence of silver nanoparticles at non-cytotoxic concentrations. HA/Ag reduced the release of nitric oxide and decreased the secretion of IL-1 and TNF-α in cells stimulated with Lipopolysaccharide (LPS). In conclusion, the inflammatory and antimicrobial capacity of the HA/Ag nanocomposites, as well as its bioactivity and low cytotoxicity make it a candidate as an implantation biomaterial for bone tissues engineering and clinical practices in orthopedic, oral and maxillofacial surgery.

Metagenomic analysis reveals the effects of long-term antibiotic pressure on sludge anaerobic digestion and antimicrobial resistance risk

Continuous stirred-tank digesters with tetracyclines and sulfonamides were operated to investigate the impacts of antibiotic pressure on sludge anaerobic digestion. The versatile methanogen Methanosarcinales and strictly hydrogenotrophic methanogen Methanobacteriales increased and decreased by 21.1% and 10.9% under antibiotic pressure, respectively. KEGG analysis revealed that hydrogenotrophic and acetoclastic methanogenesis pathways were all affected. The decrease in abundance of function genes involved in lipid metabolism, carbohydrate metabolism, and fatty acid degradation, would lead to a reduction in methane production by 25%. Network analysis indicated positive associations among tetracycline residuals, abundance of resistance genes (ARGs), and specific member of potential hosts. Over 1000 ARG subtypes were widely detected in sludge, including macrolide (28%), tetracycline (24%), fluoroquinolone (20%), and peptide (20%) resistance genes. AD process exposed to long-term antibiotic would increase the diversity and abundance of ARG, enhance the association of ARG with specific microbes, and select bacteria able to perform chemotaxis mechanism.

Interventions for primary vesicoureteric reflux.

Interventions for primary vesicoureteric reflux.

Antibiotic treatment of infections in burn patients - a systematic review

Due to the loss of the natural skin barrier function with reduced immune competence as a result of a plasma loss and the numerous intensive care interventions, burn patients are particularly at risk for infection. systematic review METHODS: A systematic review of German and English literature between 1990 and 2018 analyzes the epidemiological and diagnostic aspects as well as the therapeutic use of antibiotics in infections of burn patients in clinical trials. A total number of 53 randomized controlled clinical trials met the inclusion criteria. Various types / forms of application of antibiotic prophylaxis in burn wounds were investigated: topically, systemically (generally), systemically (perioperatively), nonabsorbable antibiotics (= selective intestinal decontamination), locally (inhaled) and all forms of administration versus control. Early postburn prophylaxis was studied in low-severity patients (six studies) and severe burn patients (seven studies). Antimicrobial prophylaxis has shown no effectiveness in the prevention of toxic shock syndrome in low grade burns, but can be useful in patients with severe burns in need for mechanical ventilation. Perioperative prophylaxis has been studied in ten studies. The benefit of long-term systemic antibiotic prophylaxis in the majority of burn patients is not evident. Mild infections in stable clinical conditions should be closely monitored, while in severe infections, international sepsis guidelines and the Tarragona principle are recommended.

A neglected causative agent in diabetic foot infection: a retrospective evaluation of 13 patients with fungal etiology

Background/aimClinicians often neglect fungal infections and do not routinely investigate deep tissue from the wound for fungal culture and sensitivity due to insufficient information in the literature. In this study, we aimed to evaluate fungal etiology of invasive fungal diabetic foot which is rarely reported in the literature.Materials and methodsThe patients who were unresponsive to antibiotic therapy and those with positive fungal in bone or deep tissue culture were enrolled in the study. Detailed hospital records were retrieved for demographics and clinical features. Results A total of 13 patients who were diagnosed with invasive fungal diabetic foot (ten females, three males, mean age 59.8 ± 9 years) were included. All of the patients had type-2 diabetes mellitus. Eleven (84.6%) patients had mixed infection. The most common cause of fungal infections of diabetic foot ulcers was the Candida species. Ten (76.9%) patients underwent amputation, two (15.4%) patients refused amputation, and one patient died before surgery. ConclusionInvasive fungal infections may also be a causative pathogen in deep tissue infections. Therefore, fungal pathogens should be considered in patients unresponsive to long-term antibiotic therapy. Early detection of fungal infections in high-risk individuals is critical for the prevention of severe consequences such as foot amputation.

Failed Debridement and Implant Retention Does Not Compromise the Success of Subsequent Staged Revision in Infected Total Knee Arthroplasty

BackgroundPeriprosthetic joint infection (PJI) is the leading cause of early revisions after total knee arthroplasty. Debridement, antibiotics, and implant retention (DAIR) procedures are often the initial treatment for PJI. However, there is concern that failed DAIR undermines the future success of revision procedures. This study aims to investigate the impact of DAIR on the success of subsequent staged revisions for PJI. MethodsA multicenter retrospective review was performed over a 15-year period. Treatment success was defined as implant retention without the use of long-term suppressive antibiotics. This was compared between patients who underwent a staged revision as the first procedure for PJI (staged-only) and patients who failed DAIR before staged revision (F-DAIR). Competing risk survival analysis was performed to compare the 2 groups and considered for patient demographics, American Society of Anesthesiologists score, organism type, body mass index, age of prosthesis, and duration of symptoms. ResultsOf 291 eligible patients, 63 underwent staged revision and 228 underwent DAIR as the first procedure for PJI. Of the 228 DAIR patients, 75 failed DAIR and underwent subsequent staged revision (F-DAIR). At mean follow-up of 6.2 years, the success rate was 72% in the F-DAIR group and 81% in the staged-only group. On survival analysis, there was no significant difference in subdistribution hazard ratio comparing the probability of failure (implant retention) in the 2 treatments groups (subdistribution hazard ratio = 0.72; 95% confidence interval 0.32-1.61; P = .42). ConclusionThis study suggested that a previously failed DAIR does not compromise the success rate of a subsequent staged revision.

Commentary on "Cross-over data supporting long-term antibiotic treatment in patients with painful lower urinary tract symptoms, pyuria, and negative urinalysis".

Commentary on "Cross-over data supporting long-term antibiotic treatment in patients with painful lower urinary tract symptoms, pyuria, and negative urinalysis".

Patient-reported complications related to peripherally inserted central catheters: a multicentre prospective cohort study

ObjectivePeripherally inserted central catheters (PICC) are frequently used to deliver medical therapies, but our knowledge regarding PICC-related complications remains incomplete. The objective of this study was to systematically elicit and...

Collagen scaffolds functionalised with copper-eluting bioactive glass reduce infection and enhance osteogenesis and angiogenesis both in vitro and in vivo

The bone infection osteomyelitis (typically by Staphylococcus aureus) usually requires a multistep procedure of surgical debridement, long-term systemic high-dose antibiotics, and – for larger defects – bone grafting. This, combined with the alarming rise in antibiotic resistance, necessitates development of alternative approaches. Herein, we describe a one-step treatment for osteomyelitis that combines local, controlled release of non-antibiotic antibacterials with a regenerative collagen-based scaffold. To maximise efficacy, we utilised bioactive glass, an established osteoconductive material with immense capacity for bone repair, as a delivery platform for copper ions (proven antibacterial, angiogenic, and osteogenic properties). Multifunctional collagen-copper-doped bioactive glass scaffolds (CuBG-CS) were fabricated with favourable microarchitectural and mechanical properties (up to 1.9-fold increase in compressive modulus over CS) within the ideal range for bone tissue engineering. Scaffolds demonstrated antibacterial activity against Staphylococcus aureus (up to 66% inhibition) whilst also enhancing osteogenesis (up to 3.6-fold increase in calcium deposition) and angiogenesis in vitro. Most significantly, when assessed in a chick embryo in vivo model, CuBG-CS not only demonstrated biocompatibility, but also a significant angiogenic and osteogenic response, consistent with in vitro studies. Collectively, these results indicate that the CuBG-CS developed here show potential as a one-step osteomyelitis treatment: reducing infection, whilst enhancing bone healing.

Infectious diseases physician attitudes to long-term antibiotic use.

Background In Australia, it is not known how much antibiotic prescribing by infectious diseases physicians is long-term, or how confident they are with the evidence behind this practice. Objective Survey Australian infectious diseases physicians to assess attitudes and prescribing practice prescribing prolonged courses of antibiotics. Methods An online questionnaire was distributed to the mailing group for the Australian Society of Infectious Diseases. Responses were collected from 29th October to 12th November 2015. Results The majority of respondents practiced in Australia as Infectious Diseases physicians, microbiologists, or trainees. 88% had prescribed long-term antibiotics. Heterogeneity was noted in the indications for prescription, including recurrent UTIs, cellulitis or chest infections, prosthetic joint infection and vascular graft infection. Beta-lactams antibiotics were prescribed most frequently. 22% of respondents had prescribed rifampicin/fusidic acid most frequently, while 11% could not identify a single antibiotic that they used most frequently, due to the heterogeneity of indications for prescribing. 95% stated that they would stop long-term antibiotic therapy if appropriate, and 74% were willing to enrol their patients into a randomised control trial looking at stopping long-term therapy. Conclusion Most infectious diseases physicians who responded to the survey prescribe long-term antibiotics, with great heterogeneity in the indications for which these antibiotics are prescribed.

National Survey on the Management of Adult Bronchiectasis in Belgium

The increasing prevalence and incidence of bronchiectasis leads to a substantial health care burden. Quality standards for the management of bronchiectasis were formulated by the British Thoracic Society following publication of guidelines in 2010. They can be used as a benchmark for quality of care. It is, however, unclear how and whether they apply outside of the UK. Between May and November 2017, we conducted an online survey among respiratory physicians caring for adult bronchiectasis patients in Belgium. About 186 cases were submitted by 117 treating physicians. Patients were mostly female (58%), of Caucasian descent (84%) with a remarkably low median age of 59.8 (IQR 47–73) years. 41% had Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus and/or Enterobacteriaceae isolated from respiratory samples in the past. 21% had three or more exacerbations, however, more than 58% were receiving long-term oral antibiotics (of which 90% azithromycin). In 40% of patients the diagnostic testing was insufficient. Surveillance of sputum bacteriology in stable patients and composing a self-management plan was missing in 53% and 68% of patients, respectively. Airway clearance techniques were implemented in 84%. Respiratory physicians complied with 60% or more to five out of the eight applicable quality standards, which is encouraging. Increasing educational act could further raise awareness and increase quality of care.

Experience in managing two challenging cases from paediatric age group

Mid-facial infection carries potential dangers of developing severe life-threatening intracranial complications. Early intervention and the awareness of possible complications essentially can help bring about a better outcome. Presented here, two paediatric cases of nasal abscesses, who developed such serious intracranialcomplications as meningitis, cavernous sinus thrombosis and brain infarction, but ultimately survived the crisis with appropriate intervening measures comprising immediate surgical intervention, efficient intensive care and long-term antibiotics. The cases were studied to ascertain a clinical course and outcome in the light ofexperience at a district hospital for further clinical application. No reconstructive surgery was performed on these patients but in short-term follow-up, no obvious facial developmental problem has been detected yet.

Recurrent cerebellar abscess secondary to cranial dermal sinus associated with dermoid cyst in children

Background: Posterior fossa dermoid cysts are rare, benign lesions whose diagnosis can be quite challenging because of their slow growth and subsequent paucity of symptoms. We present herein an unusual case of recurrent cerebellar abscesses induced by an adjacent extradural dermoid cyst with a complete occipital dermal sinus. Methods: The authors report the case of a 20-month-old girl who presented with signs of acutely raised intracranial pressure and whose head scans showed a left cerebellar hemisphere abscess associated with obstructive hydrocephalus. The patient was treated initially with an external ventricular drain, followed by burr-hole aspiration of the abscess and long-term antibiotics. Since the cerebellar abscess recurred, a posterior fossa craniotomy was performed and gross total resection of the lesion along with the dermal sinus tract and abscess contents was achieved. Histopathological analysis confirmed a dermoid tumor. Conclusions: The occurrence of recurrent cerebellar abscesses must always rise up the suspicion of an associated dermoid cyst. Neuroradiological scans should be carefully evaluated in search for this lesion. Once the diagnosis is established, radical resection of the cyst, sinus tract and infectious components is the treatment of choice.

Effects of Intervention in Patients Using Long-Term Intravenous Antibiotics

近年，抗微生物薬の不適正な使用による薬剤耐性（AMR）の問題が提起され，AMR対策アクションプランが策定された。当院においては，2017年10月より静注抗菌薬を連日15日間以上使用している患者を対象に処方医に適正使用を促す介入を行なっている。本研究は静注抗菌薬の使用実態を調査するとともに介入効果の検討を行なった。2017年6月から2018年1月に静注抗菌薬の使用を開始した入院患者1,971例（延べ2,627例）を対象とし，2017年6月から9月を介入前群，2017年10月から2018年1月を介入後群とした。長期静注抗菌薬使用患者数，総治療日数，抗菌薬使用密度（AUD），抗菌薬使用日数（DOT），系統別使用割合を比較した。長期静注抗菌薬使用患者数は介入前群で40例，介入後群では31例と減少した。総治療日数は介入前群が5.1±5.5日，介入後群は4.8±4.9日と有意差は認められなかった。AUD，DOTにおいては，ペニシリン系のAUDが増加しアミノグリコシド系は減少した。また，第3世代セフェム系およびリンコマイシン系のDOTが減少した。系統別使用割合においてはペニシリン系が増加し，第3世代セフェム系，カルバペネム系およびリンコマイシン系が減少した。長期静注抗菌薬使用患者数が減少したことや，広域抗菌薬である第3世代セフェム系，カルバペネム系の使用割合が減少し，狭域抗菌薬であるペニシリン系の全体使用量が増加したことから，介入が適正使用の推進に繋がったと考えられる。

Cross-over data supporting long-term antibiotic treatment in patients with painful lower urinary tract symptoms, pyuria and negative urinalysis

PurposeTo measure the effects of an unplanned, sudden cessation of treatment in an unselected group of patients with chronic painful LUTS managed with protracted antimicrobial treatment and to report these observational data collected from a cross-over process.Materials and methodsThe imposition of a guideline resulted in the immediate cessation of antibiotic treatment in a cohort of patients with chronic painful LUTS and microscopic pyuria. Patients were assessed before treatment withdrawal, whilst off treatment, and following reinstatement. Outcome measures included a validated symptom score, microscopic enumeration of urinary white cells and uroepithelial cells, and routine urine culture.ResultsThese patients had reported treatment-resistant, painful LUTS for a mean of 6.5 years before treatment at this centre. Treatment was stopped in 221 patients (female = 210; male = 11; mean age = 56 years; SD = 17.81). Sixty-six per cent of women were post-menopausal. After unplanned treatment cessation, 199 patients (90%; female = 188; male = 9) reported deterioration. Eleven patients required hospital care in association with disease recurrence, including acute urinary tract infection (UTI) and urosepsis. Symptom scores increased after cessation and recovered on reinitiating treatment (F = 33; df = 2; p < 0.001). Urinary leucocyte (F = 3.7; df = 2; p = 0.026) and urothelial cells counts mirrored symptomatic changes (F = 6.0; df = 2; p = 0.003). Routine urine culture results did not reflect changes in disease status.ConclusionThese data support the hypothesis that treating painful LUTS associated with pyuria with long-term antimicrobial courses, despite negative urine culture, is effective. The microscopy of fresh unspun, unstained urine to count white cells and epithelial cells offers a valid method of monitoring disease. An unplanned cessation of antibiotic therapy produced a resurgence of symptoms and lower urinary tract inflammation in patients with chronic LUTS, supporting an infective aetiology below the level of routine detection.

Successful treatment of healthcare-associated Mycobacterium chimaera prosthetic infective endocarditis: the first Spanish case report.

BackgroundSince 2011, several cases of health care-related disseminated Mycobacterium chimaera infection outbreaks have been reported subsequent to cardiac surgery. Diagnosis is difficult and the prognosis is extremely poor despite long-term antibiotic treatment and surgery.Case summaryWe report a Spanish case of M. chimaera infective endocarditis (IE) with disseminated infection. The patient was treated with long-term antibiotic therapy, valve replacement, and the novel use of interferon-gamma as adjuvant therapy. In addition, [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) was used in combination with computed tomography (CT) to facilitate the diagnosis as well as to determine the duration of antibiotics and success of treatment.DiscussionDiagnosing M. chimaera IE is difficult and requires a high index of clinical suspicion. Controlling the infection is even more difficult. Interferon-g used adjuvant to surgery and antibiotic therapy could be useful in achieving this goal. Given that the appropriate duration of antibiotics is unknown, FDG PET/CT could also be a valuable tool for determining when antibiotic therapy can be withdrawn.

A Comprehensive Review of Skull Base Osteomyelitis: Diagnostic and Therapeutic Challenges among Various Presentations.

Skull base osteomyelitis (SBO) is a complex and fatal clinical entity that is often misdiagnosed for malignancy. SBO is commonly a direct complication of otogenic, sinogenic, odontogenic, and rhinogenic infections and can present as central, atypical, or pediatric clival SBO. This review describes the clinical profile, investigational approach, and management techniques for these variants. A comprehensive literature review was performed in PubMed, MEDLINE, Research Gate, EMBASE, Wiley Online Library, and various Neurosurgical and Neurology journals with the keywords including: SBO, central or atypical SBO, fungal osteomyelitis, malignant otitis externa, temporal bone osteomyelitis, and clival osteomyelitis. Each manuscript's reference list was reviewed for potentially relevant articles. The search yielded a total of 153 articles. It was found that with early and aggressive culture guided long-term intravenous broad-spectrum antibiotic therapy decreases post-infection complications. In cases of widespread soft tissue involvement, an early aggressive surgical removal of infectious sequestra with preferentially Hyperbaric Oxygen (HBO) therapy is associated with better prognosis of disease, less neurologic sequelae and mortality rate. Complete resolution of the SBO cases may take several months. Since early treatment can improve mortality rates, it is paramount that the reporting radiologists and treating clinicians are aware of the cardinal diagnostic signs to improve clinical outcomes of the disease. It will decrease delayed diagnosis and under treatment of the condition. However, due to rarity of the condition, complete prognostic factors have not fully been analyzed and discussed in the literature.

Wybrane problemy dermatologiczno-ginekologiczne z uwzględnieniem niektórych aspektów dietetycznych u dziewcząt

Dermatological-gynaecological problems in girls are an important issue also in the practice of a family doctor. In the case of girls before menarche, vulvovaginal inflammation accounts for 75% of all gynaecology reports. However, there is a need to differentiate inflammatory diseases of the vulva from dermatoses. Symptoms of vulval diseases, which are reported by patients, often require consultation and dermatological treatment. Since dermatoses are not limited to genitals, the vulva is only one of possible locations of the disease process; therefore, the whole skin of the patient should be inspected. Vaginal and vaginal inflammation is a gynaecological problem in patients of all ages ? from neonatal period to old age. In developmental age gynaecology, it is often found in 3-10-year-old patients. The etiopathogenesis of vulvovaginitis in girls depends on child's age, systemic diseases, and often dermatological problems. For example, such factors as diabetes, long-term antibiotic therapy, immunosuppression, congenital immunodeficiency, allergic diseases and allergic rhinitis predispose to infections in girls. Lactobacillus plays an important role in bacterial protection against infection and inflammation. A balanced diet is also important.

Identification of pathogens in culture-negative infective endocarditis cases by metagenomic analysis

BackgroundPathogens identification is critical for the proper diagnosis and precise treatment of infective endocarditis (IE). Although blood and valve cultures are the gold standard for IE pathogens detection, many cases are culture-negative, especially in patients who had received long-term antibiotic treatment, and precise diagnosis has therefore become a major challenge in the clinic. Metagenomic sequencing can provide both information on the pathogenic strain and the antibiotic susceptibility profile of patient samples without culturing, offering a powerful method to deal with culture-negative cases.MethodsTo assess the feasibility of a metagenomic approach to detect the causative pathogens in resected valves from IE patients, we employed both next-generation sequencing and Oxford Nanopore Technologies MinION nanopore sequencing for pathogens and antimicrobial resistance detection in seven culture-negative IE patients. Using our in-house developed bioinformatics pipeline, we analyzed the sequencing results generated from both platforms for the direct identification of pathogens from the resected valves of seven clinically culture-negative IE patients according to the modified Duke criteria.ResultsOur results showed both metagenomics methods can be applied for the causative pathogen detection in all IE samples. Moreover, we were able to simultaneously characterize respective antimicrobial resistance features.ConclusionMetagenomic methods for IE detection can provide clinicians with valuable information to diagnose and treat IE patients after valve replacement surgery. However, more efforts should be made to optimize protocols for sample processing, sequencing and bioinformatics analysis.

312. Comparison of Short Course and Long Course of Antibiotics in Patients With Osteomyelitis: A Systemic Review and Meta-analysis

BackgroundCurrent guidelines for treatment of osteomyelitis (OM) suggest antibiotics for 3–6 weeks. However, recent studies provided conflicting evidence about the benefits of the prolonged use of antibiotics. We conducted a systemic review and meta-analysis to assess the outcomes of short- and long-term antibiotics in patients with OM.MethodsWe used three queries to retrieve literature of vertebral OM, chronic OM, and diabetic foot OM from PubMed and Embase databases until December 2017. Each query comprised medical subject headings, title/abstract keywords, and exclusion terms. Two reviewers independently screened literature for three rounds and disagreements were resolved by a third reviewer. Quality of a cohort study and that of a randomized control trial (RCT) were assessed by Newcastle-Ottawa Quality Assessment Form and a modified Jadad scale, respectively.ResultsA total of 7,192 studies were retrieved (Figure 1). Eleven observation studies and five RCTs were included for analysis, including seven articles about vertebral OM, two chronic OM, five pediatric OM, and two diabetic foot OM. Of the 11 observational studies, only five were graded as good or fair quality. Thirteen studies demonstrated no significant difference in outcomes between short- and long-term of antibiotics, while three studies showed favorable outcomes in patients taking long-term antibiotics. The aggregate odds ratio (OR) of mortality was 0.46 (95% CI, 0.21, 1.02) for observational studies and 0.90 (95% CI, 0.58, 1.41) for RCTs, showing no significant benefits of long-term antibiotics in patients with OM (Figure 2). In patients with vertebral OM, outcomes were comparable between short- and long-term of antibiotics (OR 0.51, 95% CI, 0.26, 1.01). In seven studies where only intravenous (IV) antibiotics were used, there was no significant benefit of long-term antibiotics (OR 1.12, 95% CI, 0.68, 1.83). However, in the remaining nine studies where antibiotics were transitioned from IV to oral form, there was marginal benefit of long-term oral antibiotics (OR 0.44, 95% CI, 0.22, 0.91).ConclusionBoth RCTs and observational studies demonstrated that long-term antibiotics use did not generate significantly better outcome as compared with short-term antibiotics in patients with all-cause or a specific type of OM. Disclosures All authors: No reported disclosures.