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The Cochrane Database of Systematic... Dec 2022Cystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms... (Review)
Review
BACKGROUND
Cystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms that result in lung function deterioration and early mortality in sufferers. Meticillin-resistant Staphylococcus aureus (MRSA) has emerged not only as an important infection in people who are hospitalised, but also as a potentially harmful pathogen in cystic fibrosis. Chronic pulmonary infection with MRSA is thought to confer on people with cystic fibrosis a worse clinical outcome and result in an increased rate of lung function decline. Clear guidance for MRSA eradication in cystic fibrosis, supported by robust evidence, is urgently needed. This is an update of a previous review.
OBJECTIVES
To evaluate the effectiveness of treatment regimens designed to eradicate MRSA and to determine whether the eradication of MRSA confers better clinical and microbiological outcomes for people with cystic fibrosis. To ascertain whether attempts at eradicating MRSA can lead to increased acquisition of other resistant organisms (including Pseudomonas aeruginosa), increased adverse effects from drugs, or both.
SEARCH METHODS
We identified randomised and quasi-randomised controlled trials by searching the Cochrane Cystic Fibrosis and Genetic Disorders (CFGD) Group's Cystic Fibrosis Trials Register, PubMed, MEDLINE and three clinical trials registries; by handsearching article reference lists; and through contact with experts in the field. We last searched the CFGD Group's Cystic Fibrosis Trials Register on 4 October 2021, and the ongoing trials registries on 31 January 2022.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-RCTs of any combinations of topical, inhaled, oral or intravenous antimicrobials primarily aimed at eradicating MRSA compared with placebo, standard treatment or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane and used the GRADE methodology to assess the certainty of the evidence.
MAIN RESULTS
The review includes three RCTs with 135 participants with MRSA infection. Two trials compared active treatment versus observation only and one trial compared active treatment with placebo. Active treatment versus observation In both trials (106 participants), active treatment consisted of oral trimethoprim and sulfamethoxazole combined with rifampicin. One trial administered this combination for two weeks alongside nasal, skin and oral decontamination and a three-week environmental decontamination, while the second trial administered this drug combination for 21 days with five days intranasal mupirocin. Both trials reported successful eradication of MRSA in people with cystic fibrosis, but they used different definitions of eradication. One trial (45 participants) defined MRSA eradication as negative MRSA respiratory cultures at day 28, and reported that oral trimethoprim and sulfamethoxazole combined with rifampicin may lead to a higher proportion of negative cultures compared to control (odds ratio (OR) 12.6 (95% confidence interval (CI) 2.84 to 55.84; low-certainty evidence). However, by day 168 of follow-up, there was no difference between groups in the proportion of participants who remained MRSA-negative (OR 1.17, 95% CI 0.31 to 4.42; low-certainty evidence). The second trial defined successful eradication as the absence of MRSA following treatment in at least three cultures over a period of six months. We are uncertain if the intervention led to results favouring the treatment group as the certainty of the evidence was very low (OR 2.74, 95% CI 0.64 to 11.75). There were no differences between groups in the remaining outcomes for this comparison: quality of life, frequency of exacerbations or adverse effects (all low-certainty evidence) or the change from baseline in lung function or weight (both very low-certainty evidence). The time until next positive MRSA isolate was not reported. The included trials found no differences between groups in terms of nasal colonisation with MRSA. While not a specific outcome of this review, investigators from one study reported that the rate of hospitalisation from screening through day 168 was lower with oral trimethoprim and sulfamethoxazole combined with rifampicin compared to control (rate ratio 0.22, 95% CI 0.05 to 0.72; P = 0.01). Nebulised vancomycin with oral antibiotics versus nebulised placebo with oral antibiotics The third trial (29 participants) defined eradication as a negative respiratory sample for MRSA at one month following completion of treatment. No differences were reported in MRSA eradication between treatment arms (OR 1.00, 95% CI 0.14 to 7.39; low-certainty evidence). No differences between groups were seen in lung function or adverse effects (low-certainty evidence), in quality of life (very low-certainty evidence) or nasal colonisation with MRSA. The trial did not report on the change in weight or frequency of exacerbations. AUTHORS' CONCLUSIONS: Early eradication of MRSA is possible in people with cystic fibrosis, with one trial demonstrating superiority of active MRSA treatment compared with observation only in terms of the proportion of MRSA-negative respiratory cultures at day 28. However, follow-up at three or six months showed no difference between treatment and control in the proportion of participants remaining MRSA-negative. Moreover, the longer-term clinical consequences - in terms of lung function, mortality and cost of care - remain unclear. Using GRADE methodology, we judged the certainty of the evidence provided by this review to be very low to low, due to potential biases from the open-label design, high rates of attrition and small sample sizes. Based on the available evidence, we believe that whilst early eradication of respiratory MRSA in people with cystic fibrosis is possible, there is not currently enough evidence regarding the clinical outcomes of eradication to support the use of the interventions studied.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Cystic Fibrosis; Pseudomonas aeruginosa; Anti-Bacterial Agents; Rifampin
PubMed: 36511181
DOI: 10.1002/14651858.CD009650.pub5 -
The Cochrane Database of Systematic... Jul 2018Cystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms... (Review)
Review
BACKGROUND
Cystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms that result in lung function deterioration and early mortality in sufferers.Meticillin-resistant Staphylococcus aureus (MRSA) has emerged as, not only an important infection in people who are hospitalised, but also as a potentially harmful pathogen in cystic fibrosis. Chronic pulmonary infection with MRSA is thought to confer people with cystic fibrosis with a worse clinical outcome and result in an increased rate of lung function decline. Clear guidance for MRSA eradication in cystic fibrosis, supported by robust evidence, is urgently needed. This is an update of a previous review.
OBJECTIVES
To evaluate the effectiveness of treatment regimens designed to eradicate MRSA and to determine whether the eradication of MRSA confers better clinical and microbiological outcomes for people with cystic fibrosis. To ascertain whether attempts at eradicating MRSA can lead to increased acquisition of other resistant organisms (including P aeruginosa) or increased adverse effects from drugs, or both.
SEARCH METHODS
Randomised and quasi-randomised controlled trials were identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, PubMed, MEDLINE, clinical trial registries (Clinicaltrials.gov, WHO ICTRP, ISRCTN Registry), handsearching article reference lists and through contact with experts in the field.Date of the last search of the Group's Cystic Fibrosis Trials Register: 27 July 2017.Ongoing trials registries were last searched: 07 August 2017.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials comparing any combinations of topical, inhaled, oral or intravenous antimicrobials with the primary aim of eradicating MRSA compared with placebo, standard treatment or no treatment.
DATA COLLECTION AND ANALYSIS
The authors independently assessed all search results for eligibility. They used the GRADE methodology to assess the quality of the evidence.
MAIN RESULTS
The review includes two trials with a total of 106 participants with MRSA infection. In both trials the active treatment was oral trimethoprim and sulfamethoxazole combined with rifampicin; however, one trial administered this combination for two weeks alongside nasal, skin and oral decontamination and a three-week environmental decontamination, while the second trial administered this drug combination for 21 days with five days intranasal mupirocin. In both trials the control arm was observation only.Both trials reported successful eradication of MRSA in people with CF as an outcome; however, the definition used for MRSA eradication differed. The first trial (n = 45) defined MRSA eradication as negative MRSA respiratory cultures at day 28, and reported that, when compared to control, oral trimethoprim and sulfamethoxazole combined with rifampicin may lead to a higher proportion of negative cultures, odds ratio (OR) 12.6 (95% confidence interval (CI) 2.84 to 55.84; low-certainty evidence); however, by day 168 of follow-up there was no difference in the proportion of participants who remained MRSA-negative in either treatment arm, OR 1.17 (95% CI 0.31 to 4.42) (low-quality evidence). In the second trial, successful eradication was defined as the absence of MRSA following treatment (oral co-trimoxazole and rifampicin with intranasal mupirocin or observation) in at least three cultures over a period of six months. At the time of reporting, 40 out of 61 participants had completed follow-up, but results showed no difference between groups. Eradication was achieved in 12 out 29 participants (41%) receiving active treatment, and in 9 out of 32 participants (28%) on the observation arm, OR 1.80 (95% CI 0.62 to 5.25) (very low-quality evidence).With regards to this review's secondary outcomes, these were reported in the first trial only. The trial reports that no differences were observed between the two arms in terms of pulmonary exacerbations (from screening to day 28), nasal colonisation, lung function, weight or participant-reported outcomes. While not a specific outcome of this review, investigators reported that the rate of hospitalisation from screening through day 168 was lower with oral trimethoprim and sulfamethoxazole combined with rifampicin compared to control, rate ratio 0.22 (95% CI 0.05 to 0.72) (P = 0.0102).
AUTHORS' CONCLUSIONS
Early eradication of MRSA is possible in people with cystic fibrosis, with one trial demonstrating superiority of active MRSA treatment compared with observation only in terms of the proportion of MRSA-negative respiratory cultures at day 28. However, by six months, the proportion of participants who remained MRSA-negative did not differ between treatment arms in either trial. Moreover, the longer-term clinical consequences in terms of lung function, mortality and cost of care, remain unclear.Using GRADE methodology, we judged the quality of the evidence provided by this review to be very low to low, due to potential biases from the open-label design and unclear detail reported in one trial. Based on the available evidence, it is the opinion of the authors that whilst early eradication of respiratory MRSA in people with cystic fibrosis is possible, there is not currently enough evidence regarding the clinical outcomes of eradication to support the use of the interventions studied.
Topics: Anti-Bacterial Agents; Cystic Fibrosis; Drug Therapy, Combination; Humans; Methicillin-Resistant Staphylococcus aureus; Randomized Controlled Trials as Topic; Rifampin; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 30030966
DOI: 10.1002/14651858.CD009650.pub4 -
The Cochrane Database of Systematic... Nov 2016Surgical site infections (SSI) can delay wound healing, impair cosmetic outcome and increase healthcare costs. Topical antibiotics are sometimes used to reduce microbial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Surgical site infections (SSI) can delay wound healing, impair cosmetic outcome and increase healthcare costs. Topical antibiotics are sometimes used to reduce microbial contaminant exposure following surgical procedures, with the aim of reducing SSIs.
OBJECTIVES
The primary objective of this review was to determine whether the application of topical antibiotics to surgical wounds that are healing by primary intention reduces the incidence of SSI and whether it increases the incidence of adverse outcomes (allergic contact dermatitis, infections with patterns of antibiotic resistance and anaphylaxis).
SEARCH METHODS
In May 2015 we searched: the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL. We also searched clinical trial registries for ongoing studies, and bibliographies of relevant publications to identify further eligible trials. There was no restriction of language, date of study or setting. The search was repeated in May 2016 to ensure currency of included studies.
SELECTION CRITERIA
All randomized controlled trials (RCTs) and quasi-randomised trials that assessed the effects of topical antibiotics (any formulation, including impregnated dressings) in people with surgical wounds healing by primary intention were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and independently extracted data. Two authors then assessed the studies for risk of bias. Risk ratios were calculated for dichotomous variables, and when a sufficient number of comparable trials were available, trials were pooled in a meta-analysis.
MAIN RESULTS
A total of 10 RCTs and four quasi-randomised trials with 6466 participants met the inclusion criteria. Six studies involved minor procedures conducted in an outpatient or emergency department setting; eight studies involved major surgery conducted in theatre. Nine different topical antibiotics were included. We included two three-arm trials, two four-arm trials and 10 two-arm trials. The control groups comprised; an alternative topical antibiotic (two studies), topical antiseptic (six studies) and no topical antibiotic (10 studies), which comprised inert ointment (five studies) no treatment (four studies) and one study with one arm of each.The risk of bias of the 14 studies varied. Seven studies were at high risk of bias, five at unclear risk of bias and two at low risk of bias. Most risk of bias concerned risk of selection bias.Twelve of the studies (6259 participants) reported infection rates, although we could not extract the data for this outcome from one study. Four studies (3334 participants) measured allergic contact dermatitis as an outcome. Four studies measured positive wound swabs for patterns of antimicrobial resistance, for which there were no outcomes reported. No episodes of anaphylaxis were reported. Topical antibiotic versus no topical antibioticWe pooled the results of eight trials (5427 participants) for the outcome of SSI. Topical antibiotics probably reduce the risk of SSI in people with surgical wounds healing by primary intention compared with no topical antibiotic (RR 0.61, 95% CI 0.42 to 0.87; moderate-quality evidence downgraded once for risk of bias). This equates to 20 fewer SSIs per 1000 patients treated with topical antibiotics (95% CI 7 to 29) and a number needed to treat for one additional beneficial outcome (NNTB) (i.e. prevention of one SSI) of 50.We pooled the results of three trials (3012 participants) for the outcome of allergic contact dermatitis, however this comparison was underpowered, and it is unclear whether topical antibiotics affect the risk of allergic contact dermatitis (RR 3.94, 95% CI 0.46 to 34.00; very low-quality evidence, downgraded twice for risk of bias, once for imprecision). Topical antibiotic versus antiseptic We pooled the results of five trials (1299 participants) for the outcome of SSI. Topical antibiotics probably reduce the risk of SSI in people with surgical wounds healing by primary intention compared with using topical antiseptics (RR 0.49, 95% CI 0.30 to 0.80; moderate-quality evidence downgraded once for risk of bias). This equates to 43 fewer SSIs per 1000 patients treated with topical antibiotics instead of antiseptics (95% CI 17 to 59) and an NNTB of 24.We pooled the results of two trials (541 participants) for the outcome of allergic contact dermatitis; there was no clear difference in the risk of dermatitis between topical antibiotics and antiseptics, however this comparison was underpowered and a difference cannot be ruled out (RR 0.97, 95% CI 0.52 to 1.82; very low-quality evidence, downgraded twice for risk of bias and once for imprecision). Topical antibiotic versus topical antibioticOne study (99 participants) compared mupirocin ointment with a combination ointment of neomycin/polymyxin B/bacitracin zinc for the outcome of SSI. There was no clear difference in the risk of SSI, however this comparison was underpowered (very low-quality evidence downgraded twice for risk of bias, once for imprecision).A four-arm trial involved two antibiotic arms (neomycin sulfate/bacitracin zinc/polymyxin B sulphate combination ointment versus bacitracin zinc, 219 participants). There was no clear difference in risk of SSI between the combination ointment and the bacitracin zinc ointment. The quality of evidence for this outcome was low, downgraded once for risk of bias, and once for imprecision.
AUTHORS' CONCLUSIONS
Topical antibiotics applied to surgical wounds healing by primary intention probably reduce the risk of SSI relative to no antibiotic, and relative to topical antiseptics (moderate quality evidence). We are unable to draw conclusions regarding the effects of topical antibiotics on adverse outcomes such as allergic contact dermatitis due to lack of statistical power (small sample sizes). We are also unable to draw conclusions regarding the impact of increasing topical antibiotic use on antibiotic resistance. The relative effects of different topical antibiotics are unclear.
Topics: Administration, Topical; Anti-Bacterial Agents; Anti-Infective Agents, Local; Dermatitis, Allergic Contact; Drug Resistance, Bacterial; Humans; Randomized Controlled Trials as Topic; Surgical Wound Infection; Wound Healing
PubMed: 27819748
DOI: 10.1002/14651858.CD011426.pub2