Antibiotic-associated Complications Research Articles

Challenges in designing a randomized, double-blind noninferiority trial for treatment of acne: The SD-ACNE trial.

Excessive use of antibiotics has led to development of antibiotic resistance and other antibiotic-associated complications. Dermatologists prescribe more antibiotics per clinician than any other major specialty, with much of this use for acne. Alternative acne treatments are available but are used much less often than antibiotics, at least partially because dermatologists feel that they are less effective. Spironolactone, a hormonal therapy with antiandrogen effects that can address the hormonal pathogenesis of acne, may represent a therapeutic alternative to oral antibiotics for women with acne. However, the comparative effects of spironolactone and oral antibiotics in the treatment of acne have not been definitively studied. The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation (SD-ACNE) trial aims to answer whether spironolactone, in addition to standard topical therapy, is noninferior to doxycycline (an oral antibiotic) for women with acne. Several interesting challenges arose in the development of this study, including determining acceptability of the comparative regimens to participating dermatologists, identifying data to support a noninferiority margin, and establishing a process for unblinding participants after they completed the study while maintaining the blind for study investigators. We present the scientific and clinical rationale for the decisions made in the design of the trial, including input from key stakeholders through a Delphi consensus process. The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial (NCT04582383) is being conducted at a range of community and academic sites in the United States. To maximize external validity and inform clinical practice, the study is designed with broad eligibility criteria and no prohibition of use of topical medications. Participants in the trial will be randomized to receive either spironolactone 100 mg/day or doxycycline hyclate 100 mg/day for 16 weeks. The primary outcome is the absolute decrease in inflammatory lesion count, and we have established a noninferiority margin of four inflammatory lesions. Secondary outcomes include the percentage of participants achieving Investigator Global Assessment success, change in quality of life, and microbiome changes and diversity. The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial will have substantial implications for the treatment of acne and antibiotic stewardship. In addition, this study will provide important information on the effect of these systemic agents on the development of changes to the microbiome and antibiotic resistance in a healthy population of patients.

How We Approach Difficult to Eradicate Helicobacter pylori

How We Approach Difficult to Eradicate Helicobacter pylori

Conversion of Broad-Spectrum Antimicrobial Peptides into Species-Specific Antimicrobials Capable of Precisely Targeting Pathogenic Bacteria

Currently, the majority of antibiotics in clinical use have broad activity spectra, killing pathogenic and beneficial microorganisms indiscriminately. The disruption of the ecological balance of normal flora often results in secondary infections or other antibiotic-associated complications. Therefore, targeted antimicrobial therapies capable of specifically eliminating pathogenic bacteria while retaining the protective benefits of a normal microflora would be advantageous. In this study, we successfully constructed a series of Enterococcus faecalis-targeted antimicrobial peptides from wide-spectrum antimicrobial peptide precursors. These peptides are designed based on fusion of the species-specific peptide pheromone cCF10 and modification of the active region of the antimicrobial peptide. The results showed that cCF10-C4 possessed specific antimicrobial activity against E. faecalis and was not active against other types of bacteria tested. The specificity of this hybrid peptide was shown by the absence of antimicrobial effects in the pheromone-substituted derivative. Further studies indicated that cCF10-C4 and its parent peptide C4 exert their activities by damaging cytoplasmic membrane integrity. The present study reveals the application potential of these molecules as “probiotic” antimicrobials for the control of specific bacterial infections, and it also helps to elucidate the design and construction of species-specific antimicrobials with precise targeting specificity.

Prophylactic Probiotics in Burn Patients: Risk versus Reward.

Probiotics are often used in critically ill patients to prevent antibiotic-associated complications, including Clostridium difficile colitis. However, clinical evidence of their efficacy is lacking. The objective of this study is to assess the impact of prophylactic probiotic administration on bowel function, gut microbial diversity, and nutritional markers in adult burn patients. A retrospective cohort study was done on 108 burn patients aged 18 to 89. Patients were given >1 million colony-forming units per day of Lactobacillus acidophilus and Lactobacillus rhamnosus. Testing for C. difficile was used as a surrogate marker for the presence of diarrhea. Serum C-reactive protein and prealbumin values were measured. Additionally, the gut microbial diversity of eight patients was tracked via 16S quantitative PCR before and throughout the course of a standard probiotic regimen. Patients receiving oral probiotics had more reported diarrhea in the first and second weeks of treatment. In the second week, C-reactive protein levels were increased, while serum prealbumin levels were lower in patients receiving probiotics, suggesting potential malabsorption. Additionally, there was no difference in C. difficile infection, sepsis rates, emesis, or gastric residuals, indicating an absence of therapeutic benefit for probiotic administration in burn patients. Furthermore, it was determined that no discernible benefit to gut microbial diversity was conferred by probiotic therapy. Prophylactic probiotics in burn patients are not associated with improvements in patient outcomes and may in fact be associated with an increased incidence of diarrhea and malabsorption. Additional research is needed before routine use in burn patients.

Alternative to antibiotic-associated complications from the digestive tract after treatment of urological diseases (Review)

The use of a modern enterosorbent with a prebiotic component (a combination of lignin, lactulose and microcrystalline cellulose) in urological practice helps prevent the development of complications of antibiotic therapy in the treatment of urogenital infections.

A novel treatment approach to infected nonunion of long bones without systemic antibiotics

Infected nonunion of long bones may require intravenous antibiotics over a lengthy period which may result in a high rate of complications. This study aims to assess the efficacy of local antibiotics used as a replacement to prolonged intravenous therapy. Thirteen patients with infected nonunion of long bones who failed at least one previous surgery were included. The infection was treated through extensive debridement, application of antibiotic-impregnated calcium sulphate pellets and the bone stabilized with external fixation. These patients were monitored for union and infection by clinical signs, laboratory values, and radiographs over a period of 24 months. The results support an eradication of infection and union in all patients with no antibiotic-associated complications. Local antibiotic delivery using calcium sulphate pellets provides an effective method for treatment of nonunion in long bones and is free of the complications from the intravenous route.

Extended use of perioperative antibiotics in head and neck microvascular reconstruction

PurposeMany head and neck surgical procedures are considered clean-contaminated wounds and antibiotic prophylaxis is recommended. Despite prophylaxis, the incidence of surgical site infections remains significant – especially in the setting of free tissue transfer. The antibiotic course is often of a longer duration after free tissue transfer than the recommended 24hour post-operatively. Currently, there is no consensus on appropriate antibiotic regimen or duration at this time. This study investigates the outcomes of a 7-day perioperative antibiotic regimen after microvascular reconstruction of the head and neck at our institution. Materials and methodsA retrospective review was performed of 72 patients undergoing microvascular free tissue at our institution between 09/2011 and 03/2014. The antibiotic regimen, post-operative surgical (including surgical site infections) and medical complications were noted. Our rates of complications and adverse events were compared to all surgical patients, as well as all inpatients hospital-wide with use of the University Health System Consortium database. ResultsSeventy-two subjects met inclusion criteria for this study. The majority of subjects received cefazolin/metronidazole (69.4%). Subjects with beta-lactam allergy received clindamycin (12.5%). The remainder received an alternative regimen (18.1%). All received at least 7days of antibiotics. The rate of hospital acquired C. difficile diarrhea was 0.57% hospital-wide, 1.13% in Otolaryngology patients, and 1.4% in this study. There were no instances of a multi-drug resistant infection or any adverse reactions to the administration of antibiotics. When compared with other antibiotic regimens, clindamycin was associated with a significantly increased rate of either medical or surgical infections (OR 14.38, p=0.02) and longer hospital stay (average=18days, p<0.05). ConclusionThe use of a 7-day prophylactic antibiotic regimen is not associated with an increased risk of antibiotic-associated infections, multi-drug resistant infections, or antibiotic-associated complications. The use of clindamycin is associated with increased risk of medical and surgical infections post-operatively and should be avoided in the prophylactic perioperative phase after free tissue transfer of the head and neck.

Increasing Experience with Primary Oral Medical Therapy for Mycobacterium ulcerans Disease in an Australian Cohort.

Buruli ulcer (BU) is a necrotizing infection of subcutaneous tissue that is caused by Mycobacterium ulcerans and is responsible for disfiguring skin lesions. The disease is endemic to specific geographic regions in the state of Victoria in southeastern Australia. Growing evidence of the effectiveness of antibiotic therapy for M. ulcerans disease has evolved our practice to the use of primarily oral medical therapy. An observational cohort study was performed on all confirmed M. ulcerans cases treated with primary rifampin-based medical therapy at Barwon Health between October 2010 and December 2014 and receiving 12 months of follow-up. One hundred thirty-two patients were managed with primary medical therapy. The median age of patients was 49 years, and nearly 10% had diabetes mellitus. Lesions were ulcerative in 83.3% of patients and at WHO stage 1 in 78.8% of patients. The median duration of therapy was 56 days, with 22 patients (16.7%) completing fewer than 56 days of antimicrobial treatment. Antibiotic-associated complications requiring cessation of one or more antibiotics occurred in 21 (15.9%) patients. Limited surgical debridement was performed on 30 of these medically managed patients (22.7%). Cure was achieved, with healing within 12 months, in 131 of 132 patients (99.2%), and cosmetic outcomes were excellent. Primary rifampin-based oral medical therapy for M. ulcerans disease, combined with either clarithromycin or a fluoroquinolone, has an excellent rate of cure and an acceptable toxicity profile in Australian patients. We advocate for further research to determine the optimal and safest minimum duration of medical therapy for BU.

Alcohol consumption and risk of infection after a variceal bleeding in low-risk patients.

Antibiotic prophylaxis is a cornerstone in the management of acute variceal bleeding. However, emergence of multiresistant bacteria and antibiotic-associated complications is a growing problem in cirrhosis. It has been proposed that certain low-risk populations may have good outcomes without antibiotic. We aimed to analyse the stratified risk of bacterial infection after a variceal bleeding in previously considered low-risk patients. We analysed prospective data from all consecutive cirrhotic patients with acute variceal bleeding admitted to our tertiary hospital between 2004 and 2012. All patients received somatostatin, variceal ligation and antibiotic prophylaxis. Patients were followed until day 42 or death. Patients were stratified based on Child-Pugh class. Within the low-risk strata, further one-step stratification was performed using baseline risk factors identified through logistic regression multivariate adjustment. Two hundred and fifteen patients were included. Twenty-seven patients (12.5%) developed 32 bacterial infections within 6 weeks after the index bleeding. Multivariate adjustment identified alcohol consumption as a significant risk factor for infection. Within previously considered low-risk patients (Child-Pugh A), the risk of infection was significantly higher in patients with active alcohol consumption (21.4% vs. 0% in non-drinkers, P = 0.015). The risk of infection in Child-Pugh A and B patients with non-alcohol cirrhosis receiving antibiotics was very low (2/81, 2.5%). Alcohol consumption significantly increased the risk of infection after a variceal bleeding in previously considered low-risk patients. Within Child-Pugh A class, patients with active alcohol consumption should not be considered at low risk of infection.

PD7-12 EXTENDED ANTIMICROBIAL USAGE IN PERCUTANEOUS NEPHROLITHOTOMY: INFECTIOUS AND ANTIBIOTIC RELATED COMPLICATIONS

You have accessJournal of UrologyStone Disease: Therapy I1 Apr 2014PD7-12 EXTENDED ANTIMICROBIAL USAGE IN PERCUTANEOUS NEPHROLITHOTOMY: INFECTIOUS AND ANTIBIOTIC RELATED COMPLICATIONS Boyd Viers, Patrick Cockerill, and Amy Krambeck Boyd ViersBoyd Viers More articles by this author , Patrick CockerillPatrick Cockerill More articles by this author , and Amy KrambeckAmy Krambeck More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.701AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES One-third of upper urinary tract stones harbor microorganisms. As such, current guidelines recommend perioperative antimicrobial agents up to 24-hours at the time of percutaneous renal surgery. Our goal is to evaluate perioperative infectious and antibiotic associated complications in patients receiving extended antimicrobial therapy at percutaneous nephrolithotomy (PCNL). METHODS Between 2009 and 2012, 228 consecutive PCNL patients were retrospectively reviewed. Preoperative urine and stone cultures at time of PCNL were obtained. Patients with positive cultures received extended microbe directed therapy. All others received 7 days of empiric therapy pre and postoperatively. Antibiotic related adverse events and infectious outcomes were recorded. RESULTS There were 67 (31%) infected stones and 64 (31%) patients with positive preoperative urine culture. For sterile and infected stones, mean duration of pre and postoperative antibiotic therapy was 9 vs. 14 and 10 vs. 43 days. Nitrofurantoin, trimethoprim/sulfamethoxazole, or ciprofloxacin was administered pre in 114 (50%), 32 (14%), 42 (18%) and postoperatively in 90 (39%), 42 (18%), 34 (15%) patients. Forty-three (19%) patients had 48 infectious complications: 2 (0.9%) urosepsis, 27 (12%) SIRS, 3 (1%) pneumonia, 10 (4%) UTI (of which 5 (50%) had multi-drug resistant organisms) and 5 (2%) candidiasis. There were 20 (9%) antibiotic associated complications: 8 (4%) drug rash, 2 (0.9%) swelling, 6 (3%) gastrointestinal upset, 1 (0.4%) C. diff colitis, 1 transient renal insufficiency, 1 delirium and 1 shortness of breath. There was no significant difference in antibiotic or infectious related complications based on duration of antibiotic therapy pre (p=0.50 and 0.80) or postoperatively (p=0.76 and 0.23). Patients receiving multiple antibiotics postoperatively were more likely to experience an adverse drug event (11 (19%) vs. 8 (5%); p = 0.005). In those with a positive stone culture, 17 (46%) developed an infectious complication (p = 0.05). Diabetes, struvite stones and preoperative UTI were not significant predictors of infectious or antibiotic related complications. CONCLUSIONS With a prolonged course of antibiotic therapy at the time of PCNL, our data demonstrates a low rate of postoperative infection, specifically urosepsis, and antibiotic related complications in a high risk PCNL cohort. Postoperatively, multi-antibiotic therapy was associated with increased risk of adverse drug event. Furthermore, positive stone culture increased the risk of infectious complications. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e188 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Boyd Viers More articles by this author Patrick Cockerill More articles by this author Amy Krambeck More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Antibiotic-associated complications following lower limb arthroplasty: a comparison of two prophylactic regimes

As part of a wider drive to reduce Clostridium difficile rates (CDAD), our trust switched from cefuroxime to gentamicin and flucloxacillin prophylaxis for joint replacement surgery. Anecdotal evidence suggested that we were seeing an increased incidence of acute kidney injury (AKI) following elective total hip replacement (THR) and total knee replacement (TKR) since this change. The aim of this study was to compare rates of AKI and post-operative infection between the two antibiotic regimes. We carried out a single-centre retrospective cohort study comparing 200 patients (100 THR and 100 TKR) who received cefuroxime with another age and procedure-matched group who received gentamicin and flucloxacillin (gentamicin 3 mg/kg and 5 g flucloxacillin in total). We compared rates of AKI, haemofiltration, CDAD, surgical site infection (SSI) and return to theatre for infection (RTT). Gentamicin was associated with a significant increase in AKI (1 vs. 8%, p < 0.01). More patients needed haemofiltration (0 vs. 1.5%) although this was not significant. Interestingly, when the groups were subdivided into THR and TKR, significantly more TKR patients receiving gentamicin developed AKI (0 vs. 11, p < 0.01). This difference was not significant following THR (2 vs. 5, p = 0.44). This may be related to tourniquet use in TKR. SSI and RTT were comparable. No patient developed CDAD. Gentamicin with flucloxacillin is comparable with cefuroxime in rates of SSI and RTT but is associated with a significant increase in AKI. AKI is associated with additional morbidity and mortality. This association should be considered when choosing a suitable prophylactic regime.

Characteristics and Outcomes of Outpatient Parenteral Antimicrobial Therapy at an Academic Children’s Hospital

Use of outpatient parenteral antimicrobial therapy (OPAT) in pediatrics is widespread and may be increasing. Recent data quantifying use and characteristics of pediatric OPAT are lacking. To evaluate the number of children receiving OPAT each year and their associated characteristics and outcomes, we conducted a retrospective review of all patients discharged with OPAT from the Mayo Clinic Children's Hospital between August 1, 2010 and December 31, 2011. During the study period, there were 126 pediatric hospital discharges with OPAT (2.5% of all discharges). OPAT was used most commonly to treat bone and joint (21%), bloodstream (15%), intra-abdominal (13%) and soft tissue (9%) infections. A positive culture or serology result was found in 86 (68%) OPAT courses. The most frequently used antibiotics were ceftriaxone (17%), cefazolin (16%) and cefepime (13%). The median duration of OPAT was 12 days. Thirty-six courses (29%) resulted in catheter- or antibiotic-associated complications. Weekly laboratory monitoring was more common when OPAT was managed by the infectious disease service (88%) versus other services (20%). Among 123 courses with follow-up, 109 (89%) resulted in cure, and 13 (11%) were treatment failures. At our children's hospital, 2.5% of hospitalized patients were discharged with OPAT. In one-third of OPAT courses children developed catheter- or antibiotic-associated complications. Opportunities to increase the role of pediatric infectious disease in OPAT initiation and management should be explored.

Complications Associated With Outpatient Parenteral Antibiotic Therapy in Children

The authors sought to determine the prevalence, risk factors, and clinical impact of complications associated with outpatient parenteral antimicrobial therapy (OPAT) in children. A cohort of patients ≤18 years old with infections, who received OPAT were evaluated retrospectively. Antibiotic-associated complications (AACs), catheter-associated complications (CACs), and unplanned medical care visits were the main outcome measures. Overall, 36 complications (25 CACs and 11 AACs) occurred in 32 of 98 patients. Mean age of patients, race, gender, and infecting organism did not differ between study groups. The use of OPAT for osteomyelitis was associated with complications (odds ratio = 2.69; 95% confidence interval = 0.99-7.35; P = .05). All patients, except for 4 who had complications, clinically improved by the end of OPAT. Unplanned medical visits occurred in 17 patients, 15 of which were because of CACs. Complications occurred commonly in children receiving OPAT and resulted in unplanned medical visits.

Twenty-Five Years of Research on Saccharomyces boulardii Trophic Effects: Updates and Perspectives

Saccharomyces boulardii (S. boulardii) was discovered by Henri Boulard in 1920 in Indochina. Since then, lyophilized preparations of S. boulardii have increasingly been used throughout the world, providing empirical evidence of its efficacy as an adjuvant agent to treat diarrhea and prevent antibiotic-associated complications. Since 1982, the year of the first publication [1], increasing numbers of studies have been conducted each year to determine the mechanism(s) of action of S. boulardii and to evaluate whether it has beneficial properties for the host organism. More recently, placebo-controlled, double-blind studies have demonstrated the efficacy of S. boulardii as a probiotic medication and as a biotherapeutic agent in some intestinal disorders in both children and adults. The target intestinal disorders are listen in Table 1 along with the corresponding references [2–28]. The references listed here were selected from the MEDLINE database (NIH, National Library) from among 247 publications, including both clinical and experimental studies. The number of publications on S. boulardii has increased since the mid-1990s, now reaching 15 publications per year, while very recently meta-analyses have demonstrated the beneficial effects of S. boulardii treatment, mainly in Clostridium difficileassociated disease, antibiotic-associated diarrheas, and acute infectious diarrheas. Saccharomyces boulardii is a nonpathogenic yeast widely prescribed in a lyophilized form in many countries of the world and used as a biotherapeutical agent [30–32]. The objective of the present report is to provide an update on the intestinal trophic properties of S. boulardii in endoluminal fluid and in intestinal cells at a molecular level. Several authors, using different methods of molecular biology, have shown [33–35] that S. boulardii strains are clustered within the species of S. cerevisiae, the latter having no probiotic effect. The taxonomic position of S. boulardii was evaluated by sequence analysis of the D1/D2 domain of 26S rDNA, the ITS1-5.8S rDNA-ITS2 region, and the mitochondrial cytochrome-c oxidase II gene [36]. The trophic effects of S. boulardii on human and on rat small-intestinal cells have been studied since 1986 [37] and show that oral administration of the lyophilized preparation of the yeast results in a stimulation of human and rat brush border membrane (BBM) enzymes including lactase, sucrase-isomaltase, maltase glucoamylase [37], and a,atrehalase. Incorporation of C-glucosamine into lactase precursor was stimulated by S. boulardii cells whether cells were viable or killed by heating [37]. In addition, oral therapy enhanced the intestinal synthesis of the receptor for polymeric immunoglobulins and the secretion of s-IgA [38] and transporters such as the sodium–glucose cotransporter SGLT1 with increase in glucose uptake by BBM vesicles [39]. Although the precise mechanisms by which yeast cells exert these trophic effects remain unknown there are at least three potential explanations. First, orally given yeast cells secrete directly into the endoluminal fluid enzymes such as sucrase, a,a-trehalase, aminopeptidase [40], and a phosphatase that dephosphorylates very actively the endotoxin of E. coli 55B5, resulting in an inactivation of the toxins by more than 60% as attested by the marked reduction in tissue TNF-a levels and in the absence of liver and cardiac tissue lesions [41]. J.-P. Buts (&) Laboratory of Pediatric Gastroenterology and Nutrition, Faculty of Medicine, Universite Catholique de Louvain, Tour Pasteur +3, 53, Avenue Mounier, 1200 Brussels, Belgium e-mail: buts@gype.ucl.ac.be

Recognizing and preventing antibiotic-associated complications in the critical care setting.

Antibiotics are commonly used, even overused, in the intensive care unit (ICU) patient population. These agents, though useful and often lifesaving, are associated with many toxicities. These include infusion-related problems, allergic reactions, organ-system toxicities, drug accumulation in patients with renal disease, drug interactions, antibiotic resistance, diarrhea, interference with laboratory tests, and more. Informed vigilance by the ICU nurse can be helpful in increasing the benefit/toxicity ratio associated with these agents.