A comparison of different antibiotic regimens for the treatment of infective endocarditis.

BACKGROUND: Infective endocarditis is a microbial infection of the endocardial surface of the heart. Antibiotics are the cornerstone of treatment, but due to the differences in presentation, populations affected, and the wide variety of micro-organisms that can be responsible, their use is not standardised. This is an update of a review previously published in 2016. OBJECTIVES: To assess the existing evidence about the clinical benefits and harms of different antibiotics regimens used to treat people with infective endocarditis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase Classic and Embase, LILACS, CINAHL, and the Conference Proceedings Citation Index - Science on 6 January 2020. We also searched three trials registers and handsearched the reference lists of included papers. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) assessing the effects of antibiotic regimens for treating definitive infective endocarditis diagnosed according to modified Duke's criteria. We considered all-cause mortality, cure rates, and adverse events as the primary outcomes. We excluded people with possible infective endocarditis and pregnant women. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, 'Risk of bias' assessment, and data extraction in duplicate. We constructed 'Summary of findings' tables and used GRADE methodology to assess the quality of the evidence. We described the included studies narratively. MAIN RESULTS: Six small RCTs involving 1143 allocated/632 analysed participants met the inclusion criteria of this first update. The included trials had a high risk of bias. Three trials were sponsored by drug companies. Due to heterogeneity in outcome definitions and different antibiotics used data could not be pooled. The included trials compared miscellaneous antibiotic schedules having uncertain effects for all of the prespecified outcomes in this review. Evidence was either low or very low quality due to high risk of bias and very low number of events and small sample size. The results for all-cause mortality were as follows: one trial compared quinolone (levofloxacin) plus standard treatment (antistaphylococcal penicillin (cloxacillin or dicloxacillin), aminoglycoside (tobramycin or netilmicin), and rifampicin) versus standard treatment alone and reported 8/31 (26%) with levofloxacin plus standard treatment versus 9/39 (23%) with standard treatment alone; risk ratio (RR) 1.12, 95% confidence interval (CI) 0.49 to 2.56. One trial compared fosfomycin plus imipenem 3/4 (75%) versus vancomycin 0/4 (0%) (RR 7.00, 95% CI 0.47 to 103.27), and one trial compared partial oral treatment 7/201 (3.5%) versus conventional intravenous treatment 13/199 (6.53%) (RR 0.53, 95% CI 0.22 to 1.31). The results for rates of cure with or without surgery were as follows: one trial compared daptomycin versus low-dose gentamicin plus an antistaphylococcal penicillin (nafcillin, oxacillin, or flucloxacillin) or vancomycin and reported 9/28 (32.1%) with daptomycin versus 9/25 (36%) with low-dose gentamicin plus antistaphylococcal penicillin or vancomycin; RR 0.89, 95% CI 0.42 to 1.89. One trial compared glycopeptide (vancomycin or teicoplanin) plus gentamicin with cloxacillin plus gentamicin (13/23 (56%) versus 11/11 (100%); RR 0.59, 95% CI 0.40 to 0.85). One trial compared ceftriaxone plus gentamicin versus ceftriaxone alone (15/34 (44%) versus 21/33 (64%); RR 0.69, 95% CI 0.44 to 1.10), and one trial compared fosfomycin plus imipenem versus vancomycin (1/4 (25%) versus 2/4 (50%); RR 0.50, 95% CI 0.07 to 3.55). The included trials reported adverse events, the need for cardiac surgical interventions, and rates of uncontrolled infection, congestive heart failure, relapse of endocarditis, and septic emboli, and found no conclusive differences between groups (very low-quality evidence). No trials assessed quality of life. AUTHORS' CONCLUSIONS: This first update confirms the findings of the original version of the review. Limited and low to very low-quality evidence suggests that the comparative effects of different antibiotic regimens in terms of cure rates or other relevant clinical outcomes are uncertain. The conclusions of this updated Cochrane Review were based on few RCTs with a high risk of bias. Accordingly, current evidence does not support or reject any regimen of antibiotic therapy for the treatment of infective endocarditis.

Anthelmintic drugs for treating ascariasis.

BACKGROUND: Ascaris lumbricoides is a common infection, and mainly affects children living in low-income areas. Water and sanitation improvement, health education, and drug treatment may help break the cycle of transmission, and effective drugs will reduce morbidity. OBJECTIVES: To compare the efficacy and safety of anthelmintic drugs (albendazole, mebendazole, ivermectin) for treating people with Ascaris infection. SEARCH METHODS: We searched the Cochrane Infectious Disease Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, three other databases, and reference lists of included studies, without language restrictions, up to 4 July 2019. SELECTION CRITERIA: Randomized controlled trials (RCT) that compared albendazole, mebendazole, and ivermectin in children and adults with confirmed Ascaris infection. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, assessed risk of bias, and extracted data from the included trials. A third review author checked the quality of data extraction. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) to compare dichotomous outcomes in treatment and control groups. We used the fixed-effect model for studies with low heterogeneity and the random-effects model for studies with moderate to high heterogeneity. We assessed the certainty of the evidence using the GRADE approach. We used the control rate average to provide illustrative cure rates in the comparison groups. MAIN RESULTS: We included 30 parallel-group RCTs, which enrolled 6442 participants from 17 countries across Africa, Asia, Central America and the Caribbean, and South America. Participants were from 28 days to 82 years of age, recruited from school, communities, and health facilities. Twenty studies were funded or co-funded by manufacturers, while 10 studies were independent of manufacturer funding. Twenty-two trials had a high risk of bias for one or two domains (blinding, incomplete outcome data, selective reporting). Single dose of albendazole (four trials), mebendazole (three trials) or ivermectin (one trial) was compared to placebo. Parasitological cure at 14 to 60 days was high in all the studies (illustrative cure of 93.0% in the anthelmintic group and 16.1% in the placebo group; RR 6.29, 95% CI 3.91 to 10.12; 8 trials, 1578 participants; moderate-certainty evidence). Single dose of albendazole is as effective as multiple doses of albendazole (illustrative cure of 93.2% with single dose, 94.3% with multiple doses; RR 0.98, 95% CI 0.92 to 1.05; 3 trials, 307 participants; high-certainty evidence); or as single dose of mebendazole (illustrative cure of 98.0% with albendazole, 96.9% with mebendazole; RR 1.01, 95% CI 1.00 to 1.02; 6 trials, 2131 participants; high-certainty evidence). Studies did not detect a difference between a single dose of albendazole and a single dose of ivermectin (cure rates of 87.8% with albendazole, 90.2% with ivermectin; RR 0.99, 95% CI 0.91 to 1.08; 3 trials, 519 participants; moderate-certainty evidence). Across all the studies, failure after single dose of albendazole ranged from 0.0% to 30.3%, mebendazole from 0.0% to 22.2%, and ivermectin from 0.0% to 21.6%. The egg reduction rate (ERR) measured up to 60 days after the treatment was high in all treated groups, regardless of the anthelmintic used (range 96% to 100%). It was not possible to evaluate parasitological cure by classes of infection intensity. No included trials reported complication or serious adverse events. Other adverse events were apparently similar among the compared anthelmintic groups (moderate- to low-certainty evidence). The most commonly reported other adverse events were nausea, vomiting, abdominal pain, diarrhoea, headache, and fever. AUTHORS' CONCLUSIONS: Single-dose of albendazole, mebendazole, and ivermectin all appeared effective against Ascaris lumbricoides infection, yielding high parasitological cure and large reductions in eggs excreted, with no differences detected between them. The drugs appear to be safe to treat children and adults with confirmed Ascaris infection. There is little to choose between drugs and regimens in terms of cure or adverse events.

Antibiotics for treating acute chest syndrome in people with sickle cell disease.

BACKGROUND: The clinical presentation of acute chest syndrome is similar whether due to infectious or non-infectious causes, thus antibiotics are usually prescribed to treat all episodes. Many different pathogens, including bacteria, have been implicated as causative agents of acute chest syndrome. There is no standardized approach to antibiotic therapy and treatment is likely to vary from country to country. Thus, there is a need to identify the efficacy and safety of different antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. This is an update of a Cochrane Review first published in 2007, and most recently updated in 2015. OBJECTIVES: To determine whether an empirical antibiotic treatment approach (used alone or in combination):1. is effective for acute chest syndrome compared to placebo or standard treatment;2. is safe for acute chest syndrome compared to placebo or standard treatment;Further objectives are to determine whether there are important variations in efficacy and safety:3. for different treatment regimens,4. by participant age, or geographical location of the clinical trials. SEARCH METHODS: We searched The Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 23 October 2017), African Index Medicus (1982 to 23 October 2017) and trial registries (23 October 2017).Date of most recent search of the Haemoglobinopathies Trials Register: 10 July 2019. SELECTION CRITERIA: We searched for published or unpublished randomised controlled trials. DATA COLLECTION AND ANALYSIS: Each author intended to independently extract data and assess trial quality by standard Cochrane methodologies, but no eligible randomised controlled trials were identified. MAIN RESULTS: For this update, we were unable to find any randomised controlled trials on antibiotic treatment approaches for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: This update was unable to identify randomised controlled trials on efficacy and safety of the antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. While randomised controlled trials are needed to establish the optimum antibiotic treatment for this condition, we do not envisage further trials of this intervention will be conducted, and hence the review will no longer be regularly updated.

Antibiotic therapy for adults with neurosyphilis.

BACKGROUND: Neurosyphilis is an infection of the central nervous system, caused by Treponema pallidum, a spirochete capable of infecting almost any organ or tissue in the body causing neurological complications due to the infection. This disease is a tertiary manifestation of syphilis. The first-line treatment for neurosyphilis is aqueous crystalline penicillin. However, in cases such as penicillin allergy, other regimes of antibiotic therapy can be used. OBJECTIVES: To assess the clinical effectiveness and safety of antibiotic therapy for adults with neurosyphilis. SEARCH METHODS: We searched the Cochrane Library, CENTRAL, MEDLINE, Embase, LILACS, World Health Organization International Clinical Trials Registry Platform and Opengrey up to April 2019. We also searched proceedings of eight congresses to a maximum of 10 years, and we contacted trial authors for additional information. SELECTION CRITERIA: We included randomised clinical trials that included men and women, regardless of age, with definitive diagnoses of neurosyphilis, including HIV-seropositive patients. We compared any antibiotic regime (concentration, dose, frequency, duration), compared to any other antibiotic regime for the treatment for neurosyphilis in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible trials, extracted data, and evaluated risk of bias. We resolved disagreements by involving a third review author. For dichotomous data (serological cure, clinical cure, adverse events), we presented results as summary risk ratios (RR) with 95% confidence intervals (CI). We assessed the quality of evidence using the GRADE approach. MAIN RESULTS: We identified one trial, with 36 participants​ diagnosed ​with syphilis and HIV. The participants were mainly men, with a median age of 34 years. This trial, ​funded by a pharmaceutical company, compared ceftriaxone in 18 participants (2 g daily for 10 days), with penicillin G, also in 18 participants (4 million/Units (MU)/intravenous (IV) every 4 hours for 10 days). The trial reported incomplete and inconclusive results. Three of 18 (16%) participants receiving ceftriaxone versus 2 of 18 (11%) receiving penicillin G achieved serological cure (RR 1.50; 95% CI: 0.28 to 7.93; 1 trial, 36 participants very low-quality evidence); and 8 of 18 (44%) participants receiving ceftriaxone versus 2 of 18 (18%) participants receiving penicillin G achieved clinical cure (RR 4.00; 95% CI: 0.98 to 16.30; 1 trial, 36 participants very low-quality evidence). Although more participants who received ceftriaxone achieved serological and clinical cure compared to those who received penicillin G, the evidence from this trial was insufficient to determine whether there was a difference between treatment with ceftriaxone or penicillin G.In this trial, the authors reported what would usually be adverse events as symptoms and signs in the follow-up of participants. Furthermore, this trial did not evaluate recurrence of neurosyphilis, time to recovery nor quality of life. We judged risk of bias in this clinical trial to be unclear for random sequence generation, allocation, ​and blinding of participants, and high for incomplete outcome data, potential conflicts of interest (funding bias), and other bias, due to the lack of a sample size calculation. We rated the quality of evidence as very low. AUTHORS' CONCLUSIONS: Due to low quality and insufficient evidence, it was not possible to determine whether there was a difference between treatment with ceftriaxone or Penicillin G. Also, the benefits to people without HIV and neurosyphilis are unknown, as is the ceftriaxone safety profile.Therefore, these results should be interpreted with caution. This conclusion does not mean that antibiotics should not be used for treating this clinical entity. This Cochrane Review has identified the need of adequately powered trials, which should be planned according to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) recommendations, conducted and reported as recommended by the CONSORT statement. Furthermore, the outcomes should be based on patients' perspectives taking into account Patient-Centered Outcomes Research Institute (PCORI) recommendations.

Antibiotics for treating community-acquired pneumonia in people with sickle cell disease.

BACKGROUND: As a consequence of their condition, people with sickle cell disease are at high risk of developing an acute infection of the pulmonary parenchyma called community-acquired pneumonia. Many different bacteria can cause this infection and antibiotic treatment is generally needed to resolve it. There is no standardized approach to antibiotic therapy and treatment is likely to vary from country to country. Thus, there is a need to identify the efficacy and safety of different antibiotic treatment approaches for people with sickle cell disease suffering from community-acquired pneumonia. This is an update of a previously published Cochrane Review. OBJECTIVES: To determine the efficacy and safety of the antibiotic treatment approaches (monotherapy or combined) for people with sickle cell disease suffering from community-acquired pneumonia. SEARCH METHODS: We searched The Group's Haemoglobinopathies Trials Register (01 September 2016), which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched LILACS (1982 to 01 September 2016), African Index Medicus (1982 to 20 October 2016) and WHO ICT Registry (20 October 2016). SELECTION CRITERIA: We searched for published or unpublished randomized controlled trials. DATA COLLECTION AND ANALYSIS: We intended to summarise data by standard Cochrane methodologies, but no eligible randomized controlled trials were identified. MAIN RESULTS: We were unable to find any randomized controlled trials on antibiotic treatment approaches for community-acquired pneumonia in people with sickle cell disease. AUTHORS' CONCLUSIONS: The updated review was unable to identify randomized controlled trials on efficacy and safety of the antibiotic treatment approaches for people with sickle cell disease suffering from community-acquired pneumonia. Randomized controlled trials are needed to establish the optimum antibiotic treatment for this condition. The trials regarding this issue should be structured and reported according to the CONSORT statement for improving the quality of reporting of efficacy and improved reports of harms in clinical research. Triallists should consider including the following outcomes in new trials: number of days to become afebrile; mortality; onset of pain crisis or complications of sickle cell disease following community-acquired pneumonia; diagnosis; hospitalization (admission rate and length of hospital stay); respiratory failure rate; and number of participants receiving a blood transfusion.There are no trials included in the review and we have not identified any relevant trials up to September 2016. We therefore do not plan to update this review until new trials are published.

A comparison of different antibiotic regimens for the treatment of infective endocarditis.

BACKGROUND: Infective endocarditis is a microbial infection of the endocardial surface of the heart. Antibiotics are the cornerstone of treatment, but their use is not standardised, due to the differences in presentation, populations affected and the wide variety of micro-organisms that can be responsible. OBJECTIVES: To assess the existing evidence about the clinical benefits and harms of different antibiotics regimens used to treat people with infective endocarditis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE Classic and EMBASE, LILACS, CINAHL and the Conference Proceedings Citation Index on 30 April 2015. We also searched three trials registers and handsearched the reference lists of included papers. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials assessing the effects of antibiotic regimens for treating possible infective endocarditis diagnosed according to modified Duke's criteria. We considered all-cause mortality, cure rates and adverse events as the primary outcomes. We excluded people with possible infective endocarditis and pregnant women. DATA COLLECTION AND ANALYSIS: Three review authors independently performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We constructed 'Summary of findings' tables and used GRADE methodology to assess the quality of studies. We described the included studies narratively. MAIN RESULTS: Four small randomised controlled trials involving 728 allocated/224 analysed participants met our inclusion criteria. These trials had a high risk of bias. Drug companies sponsored two of the trials. We were unable to pool the data due to the heterogeneity in outcome definitions and the different antibiotics used.The included trials compared the following antibiotic schedules. The first trial compared quinolone (levofloxacin) plus standard treatment (anti-staphylococcal penicillin (cloxacillin or dicloxacillin), aminoglycoside (tobramycin or netilmicin) and rifampicin) versus standard treatment alone reporting uncertain effects on all-cause mortality (8/31 (26%) with levofloxacin plus standard treatment versus 9/39 (23%) with standard treatment alone; RR 1.12, 95% CI 0.49 to 2.56, very low quality evidence). The second trial compared daptomycin versus low-dose gentamicin plus an anti-staphylococcal penicillin (nafcillin, oxacillin or flucloxacillin) or vancomycin. This showed uncertain effects in terms of cure rates (9/28 (32.1%) with daptomycin versus 9/25 (36%) with low-dose gentamicin plus anti-staphylococcal penicillin or vancomycin, RR 0.89 95% CI 0.42 to 1.89; very low quality evidence). The third trial compared cloxacillin plus gentamicin with a glycopeptide (vancomycin or teicoplanin) plus gentamicin. In participants receiving gentamycin plus glycopeptide only 13/23 (56%) were cured versus 11/11 (100%) receiving cloxacillin plus gentamicin (RR 0.59, 95% CI 0.40 to 0.85; very low quality evidence). The fourth trial compared ceftriaxone plus gentamicin versus ceftriaxone alone and found no conclusive differences in terms of cure (15/34 (44%) with ceftriaxone plus gentamicin versus 21/33 (64%) with ceftriaxone alone, RR 0.69, 95% CI 0.44 to 1.10; very low quality evidence).The trials reported adverse events, need for cardiac surgical interventions, uncontrolled infection and relapse of endocarditis and found no conclusive differences between comparison groups (very low quality evidence). No trials assessed septic emboli or quality of life. AUTHORS' CONCLUSIONS: Limited and very low quality evidence suggested that there were no conclusive differences between antibiotic regimens in terms of cure rates or other relevant clinical outcomes. However, because of the very low quality evidence, this needs confirmation. The conclusion of this Cochrane review was based on randomised controlled trials with high risk of bias. Accordingly, current evidence does not support or reject any regimen of antibiotic therapy for treatment of infective endocarditis.

Gloves, gowns and masks for reducing the transmission of meticillin-resistant Staphylococcus aureus (MRSA) in the hospital setting.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA; also known as methicillin-resistant S aureus) is a common hospital-acquired pathogen that increases morbidity, mortality, and healthcare costs. Its control continues to be an unresolved issue in many hospitals worldwide. The evidence base for the effects of the use of gloves, gowns or masks as control measures for MRSA is unclear. OBJECTIVES: To assess the effectiveness of wearing gloves, a gown or a mask when contact is anticipated with a hospitalised patient colonised or infected with MRSA, or with the patient's immediate environment. SEARCH METHODS: We searched the Specialised Registers of three Cochrane Groups (Wounds Group on 5 June 2015; Effective Practice and Organisation of Care (EPOC) Group on 9 July 2013; and Infectious Diseases Group on 5 January 2009); CENTRAL (The Cochrane Library 2015, Issue 6); DARE, HTA, NHS EED, and the Methodology Register (The Cochrane Library 2015, Issue 6); MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations (1946 to June week 1 2015); EMBASE (1974 to 4 June 2015); Web of Science (WOS) Core Collection (from inception to 7 June 2015); CINAHL (1982 to 5 June 2015); British Nursing Index (1985 to 6 July 2010); and ProQuest Dissertations & Theses Database (1639 to 11 June 2015). We also searched three trials registers (on 6 June 2015), references list of articles, and conference proceedings. We finally contacted relevant individuals for additional studies. SELECTION CRITERIA: Studies assessing the effects on MRSA transmission of the use of gloves, gowns or masks by any person in the hospital setting when contact is anticipated with a hospitalised patient colonised or infected with MRSA, or with the patient's immediate environment. We did not assess adverse effects or economic issues associated with these interventions.We considered any comparator to be eligible. With regard to study design, only randomised controlled trials (clustered or not) and the following non-randomised experimental studies were eligible: quasi-randomised controlled trials (clustered or not), non-randomised controlled trials (clustered or not), controlled before-and-after studies, controlled cohort before-after studies, interrupted time series studies (controlled or not), and repeated measures studies. We did not exclude any study on the basis of language or date of publication. DATA COLLECTION AND ANALYSIS: Two review authors independently decided on eligibility of the studies. Had any study having been included, two review authors would have extracted data (at least for outcome data) and assessed the risk of bias independently. We would have followed the standard methodological procedures suggested by Cochrane and the Cochrane EPOC Group for assessing risk of bias and analysing the data. MAIN RESULTS: We identified no eligible studies for this review, either completed or ongoing. AUTHORS' CONCLUSIONS: We found no studies assessing the effects of wearing gloves, gowns or masks for contact with MRSA hospitalised patients, or with their immediate environment, on the transmission of MRSA to patients, hospital staff, patients' caregivers or visitors. This absence of evidence should not be interpreted as evidence of no effect for these interventions. The effects of gloves, gowns and masks in these circumstances have yet to be determined by rigorous experimental studies, such as cluster-randomised trials involving multiple wards or hospitals, or interrupted time series studies.

Antibiotics for treating acute chest syndrome in people with sickle cell disease.

BACKGROUND: The clinical presentation of acute chest syndrome is similar whether due to infectious or non-infectious causes, thus antibiotics are usually prescribed to treat all episodes. Many different pathogens, including bacteria, have been implicated as causative agents of acute chest syndrome. There is no standardized approach to antibiotic therapy and treatment is likely to vary from country to country. Thus, there is a need to identify the efficacy and safety of different antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. This is an update of a Cochrane review first published in 2007, and previously updated in 2013. OBJECTIVES: To determine whether an empirical antibiotic treatment approach (used alone or in combination):1. is effective for acute chest syndrome compared to placebo or standard treatment;2. is safe for acute chest syndrome compared to placebo or standard treatment;Further objectives are to determine whether there are important variations in efficacy and safety:3. for different treatment regimens,4. by participant age, or geographical location of the clinical trials. SEARCH METHODS: We searched The Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 23 February 2015), African Index Medicus (1982 to 23 February 2015). and the World Health Organization International Clinical Trials Registry Platform Search Portal (23 February 2015).Date of most recent search of the Haemoglobinopathies Trials Register: 20 January 2015. SELECTION CRITERIA: We searched for published or unpublished randomised controlled trials. DATA COLLECTION AND ANALYSIS: Each author intended to independently extract data and assess trial quality by standard Cochrane Collaboration methodologies, but no eligible randomised controlled trials were identified. MAIN RESULTS: For this update, we were unable to find any randomised controlled trials on antibiotic treatment approaches for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: This update was unable to identify randomised controlled trials on efficacy and safety of the antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. Randomised controlled trials are needed to establish the optimum antibiotic treatment for this condition.

Antibiotics for treating chronic osteomyelitis in adults.

BACKGROUND: 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. OBJECTIVES: To determine the effects of different systemic antibiotic treatment regimens for treating chronic osteomyelitis in adults. SEARCH METHODS: 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. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs addressing the effects of different antibiotic treatments given after surgical debridement for chronic osteomyelitis in adults. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Interventions to improve professional adherence to guidelines for prevention of device-related infections.

BACKGROUND: Healthcare-associated infections (HAIs) are a major threat to patient safety, and are associated with mortality rates varying from 5% to 35%. Important risk factors associated with HAIs are the use of invasive medical devices (e.g. central lines, urinary catheters and mechanical ventilators), and poor staff adherence to infection prevention practices during insertion and care for the devices when in place. There are specific risk profiles for each device, but in general, the breakdown of aseptic technique during insertion and care for the device, as well as the duration of device use, are important factors for the development of these serious and costly infections. OBJECTIVES: To assess the effectiveness of different interventions, alone or in combination, which target healthcare professionals or healthcare organisations to improve professional adherence to infection control guidelines on device-related infection rates and measures of adherence. SEARCH METHODS: We searched the following electronic databases for primary studies up to June 2012: the Cochrane Effective Paractice and Organisation of Care (EPOC) Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL. We searched reference lists and contacted authors of included studies. We also searched the Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effectiveness (DARE) for related reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs), non-randomised controlled trials (NRCTs), controlled before-after (CBA) studies and interrupted time series (ITS) studies that complied with the Cochrane EPOC Group methodological criteria, and that evaluated interventions to improve professional adherence to guidelines for the prevention of device-related infections. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias of each included study using the Cochrane EPOC 'Risk of bias' tool. We contacted authors of original papers to obtain missing information. MAIN RESULTS: We included 13 studies: one cluster randomised controlled trial (CRCT) and 12 ITS studies, involving 40 hospitals, 51 intensive care units (ICUs), 27 wards, and more than 3504 patients and 1406 healthcare professionals. Six of the included studies targeted adherence to guidelines to prevent central line-associated blood stream infections (CLABSIs); another six studies targeted adherence to guidelines to prevent ventilator-associated pneumonia (VAP), and one study focused on interventions to improve urinary catheter practices. We judged all included studies to be at moderate or high risk of bias.The largest median effect on rates of VAP was found at nine months follow-up with a decrease of 7.36 (-10.82 to 3.14) cases per 1000 ventilator days (five studies and 15 sites). The one included cluster randomised controlled trial (CRCT) observed, improved urinary catheter practices five weeks after the intervention (absolute difference 12.2 percentage points), however, the statistical significance of this is unknown given a unit of analysis error. It is worth noting that N = 6 interventions that did result in significantly decreased infection rates involved more than one active intervention, which in some cases, was repeatedly administered over time, and further, that one intervention involving specialised oral care personnel showed the largest step change (-22.9 cases per 1000 ventilator days (standard error (SE) 4.0), and also the largest slope change (-6.45 cases per 1000 ventilator days (SE 1.42, P = 0.002)) among the included studies. We attempted to combine the results for studies targeting the same indwelling medical device (central line catheters or mechanical ventilators) and reporting the same outcomes (CLABSI and VAP rate) in two separate meta-analyses, but due to very high statistical heterogeneity among included studies (I(2) up to 97%), we did not retain these analyses. Six of the included studies reported post-intervention adherence scores ranging from 14% to 98%. The effect on rates of infection were mixed and the effect sizes were small, with the largest median effect for the change in level (interquartile range (IQR)) for the six CLABSI studies being observed at three months follow-up was a decrease of 0.6 (-2.74 to 0.28) cases per 1000 central line days (six studies and 36 sites). This change was not sustained over longer follow-up times. AUTHORS' CONCLUSIONS: The low to very low quality of the evidence of studies included in this review provides insufficient evidence to determine with certainty which interventions are most effective in changing professional behaviour and in what contexts. However, interventions that may be worth further study are educational interventions involving more than one active element and that are repeatedly administered over time, and interventions employing specialised personnel, who are focused on an aspect of care that is supported by evidence e.g. dentists/dental auxiliaries performing oral care for VAP prevention.

Antibiotics for treating acute chest syndrome in people with sickle cell disease.

BACKGROUND: The clinical presentation of acute chest syndrome is similar whether due to infectious or non-infectious causes, thus antibiotics are usually prescribed to treat all episodes. Many different pathogens, including bacteria, have been implicated as causative agents of acute chest syndrome. There is no standardized approach to antibiotic therapy and treatment is likely to vary from country to country. Thus, there is a need to identify the efficacy and safety of different antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. OBJECTIVES: To determine whether an empirical antibiotic treatment approach (used alone or in combination): 1. is effective for acute chest syndrome compared to placebo or standard treatment; 2. is safe for acute chest syndrome compared to placebo or standard treatment;Further objectives are to determine whether there are important variations in efficacy and safety: 3. for different treatment regimens, 4. by participant age, or geographical location of the clinical trials. SEARCH METHODS: We searched The Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 19 October 2012), African Index Medicus (1982 to 3 November 2012). and the World Health Organization International Clinical Trials Registry Platform Search Portal (19 October 2012).Date of most recent search of the Haemoglobinopathies Trials Register: 29 October 2012. SELECTION CRITERIA: We searched for published or unpublished randomised controlled trials. DATA COLLECTION AND ANALYSIS: Each author intended to independently extract data and assess trial quality by standard Cochrane Collaboration methodologies, but no eligible randomised controlled trials were identified. MAIN RESULTS: For this update, we were unable to find any randomised controlled trials on antibiotic treatment approaches for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: This update was unable to identify randomised controlled trials on efficacy and safety of the antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. Randomised controlled trials are needed to establish the optimum antibiotic treatment for this condition.

Antibiotics for treating community acquired pneumonia in people with sickle cell disease.

BACKGROUND: As a consequence of their condition, people with sickle cell disease are at high risk of developing an acute infection of the pulmonary parenchyma called community-acquired pneumonia. Many different bacteria can cause this infection and antibiotic treatment is generally needed to resolve it. There is no standardized approach to antibiotic therapy and treatment is likely to vary from country to country. Thus, there is a need to identify the efficacy and safety of different antibiotic treatment approaches for people with sickle cell disease suffering from community-acquired pneumonia. OBJECTIVES: To determine the efficacy and safety of the antibiotic treatment approaches (monotherapy or combined) for people with sickle cell disease suffering from community-acquired pneumonia. SEARCH METHODS: We searched The Group's Haemoglobinopathies Trials Register (25 May 2012), which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched LILACS (1982 to 27 April 2012), African Index Medicus (1982 to 27 April 2012) and WHO ICT Registry (27 April 2012). SELECTION CRITERIA: We searched for published or unpublished randomized controlled trials. DATA COLLECTION AND ANALYSIS: We intended to summarise data by standard Cochrane Collaboration methodologies, but no eligible randomized controlled trials were identified. MAIN RESULTS: We were unable to find any randomized controlled trials on antibiotic treatment approaches for community-acquired pneumonia in people with sickle cell disease. AUTHORS' CONCLUSIONS: The updated review was unable to identify randomized controlled trials on efficacy and safety of the antibiotic treatment approaches for people with sickle cell disease suffering from community-acquired pneumonia. Randomized controlled trials are needed to establish the optimum antibiotic treatment for this condition. The trials regarding this issue should be structured and reported according to the CONSORT statement for improving the quality of reporting of efficacy and improved reports of harms in clinical research. Triallists should consider including the following outcomes in new trials: number of days to become afebrile; mortality; onset of pain crisis or complications of SCD following CAP; diagnosis; hospitalisation (admission rate and length of hospital stay); respiratory failure rate; and number of participants receiving a blood transfusion.There are no trials included in the review and we have not identified any relevant trials up to May 2012. We therefore do not plan to update this review until new trials are published.

WITHDRAWN: Conjugate vaccines for preventing meningococcal C meningitis and septicaemia.

BACKGROUND: Meningococcal polysaccharide (MPLS) vaccines protect against Serogroup C disease, but do not produce an immune response in infants less than two years of age. This limitation can be overcome by linking C polysaccharide to carrier proteins ('conjugating'), to create meningococcal serogroup C conjugate (MCC) vaccines. In the absence of trial data, the immune response to vaccination has been considered to be a reasonable surrogate for vaccine protection. OBJECTIVES: To assess the immunogenicity, safety and efficacy of MCC vaccines for preventing meningitis and septicaemia. SEARCH STRATEGY: We searched the Cochrane Central Register Controlled Trials (CENTRAL) (The Cochrane Library 2005, issue 3); MEDLINE (1966 to September, Week 1 2005); and EMBASE (1990 to June 2005) and references of studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) in humans comparing MCC vaccines against a control vaccine or none. In the absence of any trials on vaccine efficacy, population-based observational studies about effectiveness were included. DATA COLLECTION AND ANALYSIS: Two authors independently screened the results of the literature searches, selected eligible studies, extracted the data and evaluated the quality of them. MAIN RESULTS: The studies showed that MCC vaccine was highly immunogenic in infants after two and three doses, in toddlers after one and two doses and in older age groups after one dose. In general higher titres were generated after MCC than after MPLS vaccines. Immunological hypo-responsiveness seen after repeated doses of MPLS vaccine may be overcome with MCC. Observational studies have documented a significant decline in meningococcal C disease in countries where MCC vaccines have been widely used. The timing of the vaccinations schedules, the specific conjugate used, and the vaccines given concomitantly or combined, may be important. AUTHORS' CONCLUSIONS: The MCC vaccine appears to be safe, immunogenic and able to induce immunological memory in all age groups. Observational studies strongly suggest that MCC is clinically effective.

Antibiotics for treating chronic osteomyelitis in adults.

BACKGROUND: Chronic osteomyelitis is generally treated with antibiotics and surgical debridement but can persist intermittently for years with frequent therapeutic failure. Despite advances in both antibiotics and surgical treatment, the long-term recurrence rate remains at approximately 20% to 30%. OBJECTIVES: To determine the effects of different systemic antibiotic treatment regimens for treating chronic osteomyelitis in adults. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (October 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 3), MEDLINE (January 1966 to October 2008), EMBASE (January 1980 to October 2008), LILACS (October 2008) and reference lists of relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials addressing the effects of different antibiotic treatments given after surgical debridement for chronic osteomyelitis in adults. DATA COLLECTION AND ANALYSIS: Two authors independently screened papers for inclusion, extracted data and appraised the quality of included trials. Where appropriate, we pooled data using the fixed-effect model. MAIN RESULTS: We included eight small trials (257 participants in total, with data available from 228). Study quality was often inadequate: in particular, concealment of allocation was not confirmed and there was an absence of blinding of outcome assessment. The antibiotic regimens, duration of treatment and follow-up varied between trials. Five trials compared oral versus parenteral antibiotics. There was no statistically significant difference between the two groups in the remission rate 12 or more months after treatment (risk ratio 0.94, 95% confidence interval 0.78 to 1.13; 3 trials). Antibiotic treatment for osteomyelitis was associated with moderate or severe adverse events in 4.8% of patients allocated oral antibiotics and 15.5% patients allocated parenteral antibiotics (risk ratio: 0.40, 95% confidence interval 0.13 to 1.22; 4 trials). Single trials with very few participants found no statistical significant differences for remission or adverse events for the following three comparisons: parenteral plus oral versus parenteral only administration; two oral antibiotic regimens; and two parenteral 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. AUTHORS' CONCLUSIONS: Limited evidence suggests that the method of antibiotic administration (oral versus parenteral) does not affect the rate of disease remission if the bacteria are sensitive 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.