Antibiotic Trials Research Articles

Small intestinal bacterial overgrowth in systemic sclerosis.

Systemic sclerosis is a multi-organ autoimmune disease characterized by vasculopathy and fibrosis, and it is arguably the most devastating of the rheumatological diseases. The gastrointestinal tract is the most commonly involved internal organ in systemic sclerosis. Gastrointestinal tract involvement is reported in up to 90% of SSc patients, is the leading cause of morbidity, and is the third most common cause of mortality in this disease. Among all gastrointestinal tract manifestations, small intestinal bacterial overgrowth is one manifestation that may be ameliorated and even eradicated with appropriate treatment, if recognized early. Small intestinal bacterial overgrowth occurs with a prevalence of approximately 39% in systemic sclerosis and presents with a range of non-specific gastrointestinal tract symptoms, including diarrhea, flatulence, abdominal pain, bloating, and early satiety. These manifestations occur due to an alteration and overgrowth of small intestinal bacteria occurring in the setting of gastrointestinal tract dysmotility and slow transit time. The clinical diagnosis of small intestinal bacterial overgrowth is commonly based on the presence of characteristic clinical symptoms together with a positive hydrogen breath test and response to a therapeutic trial of oral antibiotics used sequentially. Almost two-thirds of systemic sclerosis patients with small intestinal bacterial overgrowth have an improvement in their gastrointestinal tract symptoms with rotating antibiotics. Untreated small intestinal bacterial overgrowth can lead to malnutrition, and thus an important aspect of treatment is the identification and treatment of any associated vitamin and mineral deficiencies. This article focuses on small intestinal bacterial overgrowth, an important and understudied area in systemic sclerosis that remains a diagnostic and therapeutic challenge for both patients and clinicians alike.

A Randomized Trial of Prophylactic Antibiotics for Miscarriage Surgery

(Abstracted from N Engl J Med 2019;380:1012–1021) Ten percent to 20% of pregnancies end in spontaneous abortion. Products of conception are retained in some cases of spontaneous abortion, and surgical intervention is needed for their removal.

FP559Evaluating the Risk of Peritonitis Post Colonoscopy in End Stage Renal Disease Patients on Peritoneal Dialysis: A Prospective Randomized Trial of Intraperitoneal Prophylactic Antibiotic at a Single Center

FP559Evaluating the Risk of Peritonitis Post Colonoscopy in End Stage Renal Disease Patients on Peritoneal Dialysis: A Prospective Randomized Trial of Intraperitoneal Prophylactic Antibiotic at a Single Center

Antibiotic treatment for pneumonia complicating stroke: Recommendations from the pneumonia in stroke consensus (PISCES) group.

The microbiological aetiology of pneumonia complicating stroke is poorly characterised. In this second Pneumonia in Stroke ConsEnsuS statement, we propose a standardised approach to empirical antibiotic therapy in pneumonia complicating stroke, based on likely microbiological aetiology, to improve antibiotic stewardship. Systematic literature searches of multiple databases were undertaken. An evidence review and a round of consensus consultation were completed prior to a final multi-disciplinary consensus meeting in September 2017, held in Barcelona, Spain. Consensus was approached using a modified Delphi technique and defined a priori as 75% agreement between the consensus group members.Findings: No randomised trials to guide antibiotic treatment of pneumonia complicating stroke were identified. Consensus was reached for the following: (1) Stroke-associated pneumonia may be caused by organisms associated with either community-acquired or hospital-acquired pneumonia; (2) Treatment for early stroke-associated pneumonia (<72 h of stroke onset) should cover community-acquired pneumonia organisms; (3) Treatment for late stroke-associated pneumonia (≥72 h and within seven days of stroke onset) should cover community-acquired pneumonia organisms plus coliforms +/- Pseudomonas spp. if risk factors; (4) No additional antimicrobial cover is required for patients with dysphagia or aspiration; (5) Pneumonia occurring after seven days from stroke onset should be treated as for hospital-acquired pneumonia; (6) Treatment should continue for at least seven days for each of these scenarios. Consensus recommendations for antibiotic treatment of the spectrum of pneumonia complicating stroke are proposed. However, there was limited evidence available to formulate consensus on choice of specific antibiotic class for pneumonia complicating stroke. Further studies are required to inform evidence-based treatment of stroke-associated pneumonia including randomised trials of antibiotics and validation of candidate biomarkers.

Serum Procalcitonin Levels in Children with Clinical Syndromes for Targeting Antibiotic Use at an Emergency Department of a Kenyan Hospital.

Serum procalcitonin (PCT) was measured in 228 children aged 1 month to 15 years at an emergency department of a hospital located in an area without local malaria transmission in children with suspected infections; 21% (49) children had a clinical syndrome for suspected bacterial infections (Syndrome +ve). In children with Syndrome+ve criteria, 27/49 (55.1%) had PCT ≥ 0.5 μg/l but only 59/179 (32.9%) of those Syndrome +ve had abnormal PCT, χ 2 = 8.0, p = 0.005; positive likelihood ratio = 2.0 [95% confidence interval (CI) 1.2–3.3]; negative likelihood ratio = 0.8 (95% CI 0.7–1.0). In patients with pneumonia, 9/15 (60%) with severe pneumonia had PCT ≥ 0.5 μg/l compared to 11/21 (52.4%) with non-severe pneumonia, χ 2 = 0.2, p = 0.65. Children with clinical signs of pneumonia or clinical signs suggestive of bacterial infections fulfilling clinical syndromic definitions for suspected bacterial infections commonly have elevated PCT level. PCT levels are associated with disease severity and antibiotic trials guided by PCT levels may be needed where cultures are not available.

Antimicrobial Susceptibility Patterns of Salmonella Species in Southern Pakistan.

IntroductionTyphoid fever is a major infectious disease among the pediatric population of Pakistan. With inappropriate use of antibiotics and rising trends of multidrug-resistant (MDR) and extended drug-resistant (XDR) typhoid, it is becoming a public health emergency. This study evaluated the current trends in antibiotic susceptibilities to Salmonella (S) typhi and paratyphi A, B, and C in southern Pakistan.Materials and methodsThis cross-sectional study, conducted in the Pediatrics Department, Civil Hospital, Jamshoro from July to December 2018, included children with S. typhi and S. paratyphi A and B strains isolated from the laboratory-based culture of blood samples.ResultsThere were 223 (81.1%) children with S. typhi and 52 (18.9%) with S. paratyphi isolates. Their mean age was 5 ± 3 years. The most common age group with S. typhi strains was two to five years (n = 102; 37.1%). Previous trials of antibiotics were taken by 162 (58.9%) children; 65 (40.1%) of these were physician-prescribed. Cefixime was most commonly taken (66.6%), followed by ciprofloxacin (33.3%). Cefixime and ceftriaxone showed 60.9% and 65.8% sensitivity, respectively. Ciprofloxacin sensitivity was seen in 50.1% S. typhi isolates. There were six (2.6%) cases of MDR typhoid and two (0.9%) cases of XDR typhoid.ConclusionResistance to second-line antityphoid agents is increasing. Therefore, there is a need to modify prescribing behavior. The outbreak of XDR typhoid among children is an alarming public health concern for Pakistan. Widespread antibiotic stewardship programs must be conducted.

Microdeformational wound therapy: A novel option to salvage complex wounds associated with the Nuss procedure

BackgroundComplex wounds associated with the Nuss procedure are a resource intensive complication that may lead to significant morbidity with potential removal of the implanted device and abandonment of the repair. We report our management technique of this complication utilizing microdeformational wound therapy (MDWT) that is safe, is efficacious and allows for salvage of the repair. Operative techniqueWe defined a complex wound as a wound that became suppurative and drained in the postoperative period and failed to resolve with a trial of conventional wound management and antibiotics. Upon recognition of a complex wound, we recommend an initial operative wound debridement. This allows wound cultures, wound assessment and precise initiation of MDWT. It is not uncommon to have exposed hardware in the wound early in the course of therapy. Metal allergy must be excluded. The patient is transitioned to oral antibiotics following resolution of the acute process. MDWT is performed until the wounds are completely epithelialized with no clinical signs of drainage or infection. The average length of MDWT in our patients was 39 days. Following complete wound healing the patients are maintained on antibiotics until implant removal. ConclusionsThe use of microdeformational wound therapy in complex wounds associated with the Nuss procedure is a safe and effective modality. The technique may reduce the likelihood of implant removal with potential recurrent pectus excavatum. Type of studyOperative technique. Level of evidenceLevel IV, case series with no comparison group

A Randomized Trial of Prophylactic Antibiotics for Miscarriage Surgery

BackgroundSurgical intervention is needed in some cases of spontaneous abortion to remove retained products of conception. Antibiotic prophylaxis may reduce the risk of pelvic infection, which is an important complication of this surgery, particularly in low-resource countries.MethodsWe conducted a double-blind, placebo-controlled, randomized trial investigating whether antibiotic prophylaxis before surgery to complete a spontaneous abortion would reduce pelvic infection among women and adolescents in low-resource countries. We randomly assigned patients to a single preoperative dose of 400 mg of oral doxycycline and 400 mg of oral metronidazole or identical placebos. The primary outcome was pelvic infection within 14 days after surgery. Pelvic infection was defined by the presence of two or more of four clinical features (purulent vaginal discharge, pyrexia, uterine tenderness, and leukocytosis) or by the presence of one of these features and the clinically identified need to administer antibiotics. The definition of pelvic infection was changed before the unblinding of the data; the original strict definition was two or more of the clinical features, without reference to the administration of antibiotics.ResultsWe enrolled 3412 patients in Malawi, Pakistan, Tanzania, and Uganda. A total of 1705 patients were assigned to receive antibiotics and 1707 to receive placebo. The risk of pelvic infection was 4.1% (68 of 1676 pregnancies) in the antibiotics group and 5.3% (90 of 1684 pregnancies) in the placebo group (risk ratio, 0.77; 95% confidence interval [CI], 0.56 to 1.04; P=0.09). Pelvic infection according to original strict criteria was diagnosed in 1.5% (26 of 1700 pregnancies) and 2.6% (44 of 1704 pregnancies), respectively (risk ratio, 0.60; 95% CI, 0.37 to 0.96). There were no significant between-group differences in adverse events.ConclusionsAntibiotic prophylaxis before miscarriage surgery did not result in a significantly lower risk of pelvic infection, as defined by pragmatic broad criteria, than placebo. (Funded by the Medical Research Council and others; AIMS Current Controlled Trials number, ISRCTN97143849.)

How to Identify Exposed Women Who Are Infected with Neisseria gonorrhoeae.

Treatment trials of antibiotics for Neisseria gonorrhoeae infections frequently enroll primarily men with urethritis, as the diagnosis of acute gonococcal infection in men with urethritis is easily made by Gram stain of the urethral exudate, followed by confirmatory culture or nucleic acid amplification tests (NAATs). Enrolling women in treatment trials is of great importance, but N. gonorrhoeae cervical infections cause nonspecific symptoms. This makes it difficult to conduct interventional trials, as large numbers of women with nonspecific symptoms need to be screened for infection. Gram stain of cervical secretions has a strikingly low sensitivity, and culture and/or NAAT results are not available at the time of screening. This necessitates recall and delayed treatment of infected women who may not return and who may spread the infection during the interval. In this chapter we present an algorithm, derived from a comparison of women who did, or did not, become infected during exposure, which identifies those women who are highly likely to be infected before culture and/or NAAT results are available. The algorithm provides an efficient way to conduct interventional trials in women without the problem of recall and delayed treatment.

Consensus group on the design, analysis and reporting of antibiotic stewardship trials – MRC

Improving antibiotic stewardship [Interview] Professor Martin Llewelyn and Dr Valentijn Schweitzer discuss antibiotic stewardship and explain why there is an urgent need to develop recommendations for better research in this field

Antibiotic prescribing for the older adult: beliefs and practices in primary care.

Older adults suffer high morbidity and mortality following serious infections, and hospital admissions with these conditions are increasingly common. Antibiotic prescribing in the older adult population, especially in long-term care facilities, has been argued to be inappropriately high. In order to develop the evidence base and provide support to GPs in achieving antimicrobial stewardship in older adults it is important to understand their attitudes and beliefs toward antibiotic prescribing in this population. To understand the attitudes and beliefs held by GPs regarding antibiotic prescribing in older adults. Semi-structured qualitative interviews were conducted with 28 GPs working in the UK. Data analysis followed a modified framework approach. GPs described antibiotic prescribing in older adults as differing from prescribing in other age groups in a number of ways, including prescribing broad-spectrum, longer and earlier antibiotics in this population. There were also rationales for situations where antibiotics were prescribed despite there being no clear diagnosis of infection. Trials of antibiotics were used both as diagnostic aids and in an attempt to avoid admission. The risks of antibiotics were understood, but in some cases restrictions on antibiotic use were thought to hamper optimal management of infection in this age group. Diagnosing serious infections in older adults is challenging and antibiotic prescribing practices reflect this challenge, but also reflect an absence of clear guidance or evidence. Research that can fill the gaps in the evidence base is required in order to support GPs with their critical antimicrobial stewardship role in this population.

Assessment of the Perceived Acceptability of an Early Enrollment Strategy Using Advance Consent in Health Care–Associated Pneumonia

Better treatment options are needed in life-threatening infections, including health care-associated pneumonia. Enrolling patients in antibacterial clinical trials before diagnosis may circumvent existing time-to-enrollment constraints. However, the acceptability of an early enrollment strategy using advance consent is unknown. To assess the perceived acceptability of an early enrollment strategy for enrolling patients in an antibacterial clinical trial before a pneumonia diagnosis. This qualitative, descriptive study used semistructured telephone interviews. Framed within a planned noninferiority pneumonia antibiotic trial, an early enrollment strategy was described and perceptions were assessed. Using this strategy, patients give consent to enroll before developing pneumonia, to be monitored by study staff, and to be randomly assigned a study antibiotic if pneumonia develops. All interviews were audiorecorded, transcribed verbatim, and analyzed using applied thematic analysis. Fifty-two key stakeholders from across the United States, including 18 patients at risk of pneumonia, 12 caregivers, 10 representatives of institutional review boards, 7 investigators, and 5 study coordinators, were interviewed from June 20 to August 19, 2016. Perceived acceptability of the early enrollment strategy. Among the 52 stakeholders interviewed (ages 29-75 years; 14 women), patients and caregivers expressed no concerns about patients being approached about participation before developing pneumonia; however, some patients may experience anxiety on learning about their risk for pneumonia. No concerns with study staff accessing patients' medical records were expressed. The clarity of consent information was important for understanding the study rather than having the condition under investigation. Among patients, caregivers, and institutional review board representatives, preferences varied regarding opt-out and precedent autonomy procedures. Nearly all patients would be willing to join a trial using the early enrollment strategy and caregivers would be willing to provide proxy consent. Institutional review board representatives were supportive of the strategy and made recommendations for the study protocol, primarily around informed consent. Investigators and study coordinators believed the strategy would not be burdensome and offered suggestions to ensure its feasibility. Results of the study suggest that the early enrollment strategy is acceptable. Future research should evaluate whether the strategy improves enrollment rates in registrational pneumonia trials and in trials of other acute infection syndromes with narrow enrollment windows and/or patients with transient decisional incapacity.

Colo-Pro: a pilot randomised controlled trial to compare standard bolus-dosed cefuroxime prophylaxis to bolus-continuous infusion\u2013dosed cefuroxime prophylaxis for the prevention of infections after colorectal surgery

Standard bolus-dosed antibiotic prophylaxis may not inhibit growth of antibiotic resistant colonic bacteria, a cause of SSIs after colorectal surgery. An alternative strategy is continuous administration of antibiotic throughout surgery, maintaining concentrations of antibiotics that inhibit growth of resistant bacteria. This study is a pilot comparing bolus-continuous infusion with bolus-dosed cefuroxime prophylaxis in colorectal surgery. This is a pilot randomised controlled trial in which participants received cefuroxime bolus-infusion (intervention arm) targeting free serum cefuroxime concentrations of 64 mg/L, or 1.5 g cefuroxime as a bolus dose four-hourly (standard arm). Patients in both arms received metronidazole (500 mg intravenously). Eligible participants were adults undergoing colorectal surgery expected to last for over 2 h. Results were analysed on an intention-to-treat basis. The study was successfully piloted, with 46% (90/196) of eligible patients recruited and 89% (80/90) of participants completing all components of the protocol. A trialled bolus-continuous dosing regimen was successful in maintaining free serum cefuroxime concentrations of 64 mg/L. No serious adverse reactions were identified. Rates of SSIs (superficial and deep SSIs) were lower in the intervention arm than the standard treatment arm (24% (10/42) vs. 30% (13/43)), as were infection within 30 days of operation (41% (17/43) vs 51% (22/43)) and urinary tract infections (2% (1/42) vs. 9% (4/43)). These infection rates can be used to power future clinical trials. This study demonstrates the feasibility of cefuroxime bolus-continuous infusion of antibiotic prophylaxis trials, and provides safety data for infusions targeting free serum cefuroxime concentrations of 64 mg/L. Trial registration: NCT02445859.

Evaluating the Risk of Peritonitis Post Colonoscopy in End Stage Renal Disease Patients on Peritoneal Dialysis: A Prospective Randomized Trial of Intraperitoneal Prophylactic Antibiotic at a Single Center

Evaluating the Risk of Peritonitis Post Colonoscopy in End Stage Renal Disease Patients on Peritoneal Dialysis: A Prospective Randomized Trial of Intraperitoneal Prophylactic Antibiotic at a Single Center

Nanoparticle microarray for high-throughput microbiome metabolomics using matrix-assisted laser desorption ionization mass spectrometry.

A high-throughput matrix-assisted laser desorption/ionization mass spectrometry (MALDI)-MS-based metabolomics platform was developed using a pre-fabricated microarray of nanoparticles and organic matrices. Selected organic matrices, inorganic nanoparticle (NP) suspensions, and sputter coated metal NPs, as well as various additives, were tested for metabolomics analysis of the turkey gut microbiome. Four NPs and one organic matrix were selected as the optimal matrix set: α-cyano-4-hydroycinnamic acid, Fe3O4 and Au NPs in positive ion mode with 10mM sodium acetate, and Cu and Ag NPs in negative ion mode with no additive. Using this set of five matrices, over two thousand unique metabolite features were reproducibly detected across intestinal samples from turkeys fed a diet amended with therapeutic or sub-therapeutic antibiotics (200g/ton or 50g/ton bacitracin methylene disalicylate (BMD), respectively), or non-amended feed. Among the thousands of unique features, 56 of them were chemically identified using MALDI-MS/MS, with the help of in-parallel liquid chromatography (LC)-MS/MS analysis. Lastly, as a proof of concept application, this protocol was applied to 52 turkey cecal samples at three different time points from the antibiotic feed trial. Statistical analysis indicated variations in the metabolome of turkeys with different ages or treatments. Graphical abstract ᅟ.

Sequential, Multiple-Assignment, Randomized Trials for COMparing Personalized Antibiotic StrategieS (SMART-COMPASS).

Patient management is not based on a single decision. Rather, it is dynamic: based on a sequence of decisions, with therapeutic adjustments made over time. Adjustments are personalized: tailored to individual patients as new information becomes available. However, strategies allowing for such adjustments are infrequently studied. Traditional antibiotic trials are often nonpragmatic, comparing drugs for definitive therapy when drug susceptibilities are known. COMparing Personalized Antibiotic StrategieS (COMPASS) is a trial design that compares strategies consistent with clinical practice. Strategies are decision rules that guide empiric and definitive therapy decisions. Sequential, multiple-assignment, randomized (SMART) COMPASS allows evaluation when there are multiple, definitive therapy options. SMART COMPASS is pragmatic, mirroring clinical, antibiotic-treatment decision-making and addressing the most relevant issue for treating patients: identification of the patient-management strategy that optimizes the ultimate patient outcomes. SMART COMPASS is valuable in the setting of antibiotic resistance, when therapeutic adjustments may be necessary due to resistance.

Power priors based on multiple historical studies for binary outcomes.

Incorporating historical information into the design and analysis of a new clinical trial has been the subject of much recent discussion. For example, in the context of clinical trials of antibiotics for drug resistant infections, where patients with specific infections can be difficult to recruit, there is often only limited and heterogeneous information available from the historical trials. To make the best use of the combined information at hand, we consider an approach based on the multiple power prior that allows the prior weight of each historical study to be chosen adaptively by empirical Bayes. This choice of weight has advantages in that it varies commensurably with differences in the historical and current data and can choose weights near 1 if the data from the corresponding historical study are similar enough to the data from the current study. Fully Bayesian approaches are also considered. The methods are applied to data from antibiotics trials. An analysis of the operating characteristics in a binomial setting shows that the proposed empirical Bayes adaptive method works well, compared to several alternative approaches, including the meta-analytic prior.

Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults.

Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults.

Antibiotics for treating scrub typhus.

BackgroundScrub typhus, an important cause of acute fever in Asia, is caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Antibiotics currently used to treat scrub typhus include tetracyclines, chloramphenicol, macrolides, and rifampicin.ObjectivesTo assess and compare the effects of different antibiotic regimens for treatment of scrub typhus.Search methodsWe searched the following databases up to 8 January 2018: the Cochrane Infectious Diseases Group specialized trials register; CENTRAL, in the Cochrane Library (2018, Issue 1); MEDLINE; Embase; LILACS; and the metaRegister of Controlled Trials (mRCT). We checked references and contacted study authors for additional data. We applied no language or date restrictions.Selection criteriaRandomized controlled trials (RCTs) or quasi‐RCTs comparing antibiotic regimens in people with the diagnosis of scrub typhus based on clinical symptoms and compatible laboratory tests (excluding the Weil‐Felix test).Data collection and analysisFor this update, two review authors re‐extracted all data and assessed the certainty of evidence. We meta‐analysed data to calculate risk ratios (RRs) for dichotomous outcomes when appropriate, and elsewhere tabulated data to facilitate narrative analysis.Main resultsWe included six RCTs and one quasi‐RCT with 548 participants; they took place in the Asia‐Pacific region: Korea (three trials), Malaysia (one trial), and Thailand (three trials). Only one trial included children younger than 15 years (N = 57). We judged five trials to be at high risk of performance and detection bias owing to inadequate blinding. Trials were heterogenous in terms of dosing of interventions and outcome measures. Across trials, treatment failure rates were low.Two trials compared doxycycline to tetracycline. For treatment failure, the difference between doxycycline and tetracycline is uncertain (very low‐certainty evidence). Doxycycline compared to tetracycline may make little or no difference in resolution of fever within 48 hours (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.90 to 1.44, 55 participants; one trial; low‐certainty evidence) and in time to defervescence (116 participants; one trial; low‐certainty evidence). We were unable to extract data for other outcomes.Three trials compared doxycycline versus macrolides. For most outcomes, including treatment failure, resolution of fever within 48 hours, time to defervescence, and serious adverse events, we are uncertain whether study results show a difference between doxycycline and macrolides (very low‐certainty evidence). Macrolides compared to doxycycline may make little or no difference in the proportion of patients with resolution of fever within five days (RR 1.05, 95% CI 0.99 to 1.10; 185 participants; two trials; low‐certainty evidence). Another trial compared azithromycin versus doxycycline or chloramphenicol in children, but we were not able to disaggregate date for the doxycycline/chloramphenicol group.One trial compared doxycycline versus rifampicin. For all outcomes, we are uncertain whether study results show a difference between doxycycline and rifampicin (very low‐certainty evidence). Of note, this trial deviated from the protocol after three out of eight patients who had received doxycycline and rifampicin combination therapy experienced treatment failure.Across trials, mild gastrointestinal side effects appeared to be more common with doxycycline than with comparator drugs.Authors' conclusionsTetracycline, doxycycline, azithromycin, and rifampicin are effective treatment options for scrub typhus and have resulted in few treatment failures. Chloramphenicol also remains a treatment option, but we could not include this among direct comparisons in this review.Most available evidence is of low or very low certainty. For specific outcomes, some low‐certainty evidence suggests there may be little or no difference between tetracycline, doxycycline, and azithromycin as treatment options. Given very low‐certainty evidence for rifampicin and the risk of inducing resistance in undiagnosed tuberculosis, clinicians should not regard this as a first‐line treatment option. Clinicians could consider rifampicin as a second‐line treatment option after exclusion of active tuberculosis.Further research should consist of additional adequately powered trials of doxycycline versus azithromycin or other macrolides, trials of other candidate antibiotics including rifampicin, and trials of treatments for severe scrub typhus. Researchers should standardize diagnostic techniques and reporting of clinical outcomes to allow robust comparisons.11 April 2019Up to dateAll studies incorporated from most recent searchAll eligible published studies found in the last search (8 Jan, 2018) were included and four ongoing studies have been identified (see 'Characteristics of ongoing studies' section)

Antibiotics for acute rhinosinusitis in adults.

Acute rhinosinusitis is an acute infection of the nasal passages and paranasal sinuses that lasts less than four weeks. Diagnosis of acute rhinosinusitis is generally based on clinical signs and symptoms in ambulatory care settings. Technical investigations are not routinely performed, nor are they recommended in most countries. Some trials show a trend in favour of antibiotics, but the balance of benefit versus harm is unclear.We merged two Cochrane Reviews for this update, which comprised different approaches with overlapping populations, resulting in different conclusions. For this review update, we maintained the distinction between populations diagnosed by clinical signs and symptoms, or imaging. To assess the effects of antibiotics versus placebo or no treatment in adults with acute rhinosinusitis in ambulatory care settings. We searched CENTRAL (2017, Issue 12), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (January 1950 to January 2018), Embase (January 1974 to January 2018), and two trials registers (January 2018). We also checked references from identified trials, systematic reviews, and relevant guidelines. Randomised controlled trials of antibiotics versus placebo or no treatment in people with rhinosinusitis-like signs or symptoms or sinusitis confirmed by imaging. Two review authors independently extracted data about cure and side effects and assessed the risk of bias. We contacted trial authors for additional information as required. We included 15 trials involving 3057 participants. Of the 15 included trials, 10 appeared in our 2012 review, and five (631 participants) are legacy trials from merging two reviews. No new studies were included from searches for this update. Overall, risk of bias was low. Without antibiotics, 46% of participants with rhinosinusitis, whether or not confirmed by radiography, were cured after 1 week and 64% after 14 days. Antibiotics can shorten time to cure, but only 5 to 11 more people per 100 will be cured faster if they receive antibiotics instead of placebo or no treatment: clinical diagnosis (odds ratio (OR) 1.25, 95% confidence interval (CI) 1.02 to 1.54; number needed to treat for an additional beneficial outcome (NNTB) 19, 95% CI 10 to 205; I² = 0%; 8 trials; high-quality evidence) and diagnosis confirmed by radiography (OR 1.57, 95% CI 1.03 to 2.39; NNTB 10, 95% CI 5 to 136; I² = 0%; 3 trials; moderate-quality evidence). Cure rates with antibiotics were higher when a fluid level or total opacification in any sinus was found on computed tomography (OR 4.89, 95% CI 1.75 to 13.72; NNTB 4, 95% CI 2 to 15; 1 trial; moderate-quality evidence). Purulent secretion resolved faster with antibiotics (OR 1.58, 95% CI 1.13 to 2.22; NNTB 10, 95% CI 6 to 35; I² = 0%; 3 trials; high-quality evidence). However, 13 more people experienced side effects with antibiotics compared to placebo or no treatment (OR 2.21, 95% CI 1.74 to 2.82; number needed to treat for an additional harmful outcome (NNTH) 8, 95% CI 6 to 12; I² = 16%; 10 trials; high-quality evidence). Five fewer people per 100 will experience clinical failure if they receive antibiotics instead of placebo or no treatment (Peto OR 0.48, 95% CI 0.36 to 0.63; NNTH 19, 95% CI 15 to 27; I² = 21%; 12 trials; high-quality evidence). A disease-related complication (brain abscess) occurred in one participant (of 3057) one week after receiving open antibiotic therapy (clinical failure, control group). The potential benefit of antibiotics to treat acute rhinosinusitis diagnosed either clinically (low risk of bias, high-quality evidence) or confirmed by imaging (low to unclear risk of bias, moderate-quality evidence) is marginal and needs to be seen in the context of the risk of adverse effects. Considering antibiotic resistance, and the very low incidence of serious complications, we conclude there is no place for antibiotics for people with uncomplicated acute rhinosinusitis. We could not draw conclusions about children, people with suppressed immune systems, and those with severe sinusitis, because these populations were not included in the available trials.