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The Cochrane Database of Systematic... Jun 2023Respiratory tract infections with Pseudomonas aeruginosa occur in most people with cystic fibrosis (CF). Established chronic P aeruginosa infection is virtually... (Review)
Review
BACKGROUND
Respiratory tract infections with Pseudomonas aeruginosa occur in most people with cystic fibrosis (CF). Established chronic P aeruginosa infection is virtually impossible to eradicate and is associated with increased mortality and morbidity. Early infection may be easier to eradicate. This is an updated review.
OBJECTIVES
Does giving antibiotics for P aeruginosa infection in people with CF at the time of new isolation improve clinical outcomes (e.g. mortality, quality of life and morbidity), eradicate P aeruginosa infection, and delay the onset of chronic infection, but without adverse effects, compared to usual treatment or an alternative antibiotic regimen? We also assessed cost-effectiveness.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and conference proceedings. Latest search: 24 March 2022. We searched ongoing trials registries. Latest search: 6 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of people with CF, in whom P aeruginosa had recently been isolated from respiratory secretions. We compared combinations of inhaled, oral or intravenous (IV) antibiotics with placebo, usual treatment or other antibiotic combinations. We excluded non-randomised trials and cross-over trials.
DATA COLLECTION AND ANALYSIS
Two authors independently selected trials, assessed risk of bias and extracted data. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 11 trials (1449 participants) lasting between 28 days and 27 months; some had few participants and most had relatively short follow-up periods. Antibiotics in this review are: oral - ciprofloxacin and azithromycin; inhaled - tobramycin nebuliser solution for inhalation (TNS), aztreonam lysine (AZLI) and colistin; IV - ceftazidime and tobramycin. There was generally a low risk of bias from missing data. In most trials it was difficult to blind participants and clinicians to treatment. Two trials were supported by the manufacturers of the antibiotic used. TNS versus placebo TNS may improve eradication; fewer participants were still positive for P aeruginosa at one month (odds ratio (OR) 0.06, 95% confidence interval (CI) 0.02 to 0.18; 3 trials, 89 participants; low-certainty evidence) and two months (OR 0.15, 95% CI 0.03 to 0.65; 2 trials, 38 participants). We are uncertain whether the odds of a positive culture decrease at 12 months (OR 0.02, 95% CI 0.00 to 0.67; 1 trial, 12 participants). TNS (28 days) versus TNS (56 days) One trial (88 participants) comparing 28 days to 56 days TNS treatment found duration of treatment may make little or no difference in time to next isolation (hazard ratio (HR) 0.81, 95% CI 0.37 to 1.76; low-certainty evidence). Cycled TNS versus culture-based TNS One trial (304 children, one to 12 years old) compared cycled TNS to culture-based therapy and also ciprofloxacin to placebo. We found moderate-certainty evidence of an effect favouring cycled TNS therapy (OR 0.51, 95% CI 0.31 to 0.82), although the trial publication reported age-adjusted OR and no difference between groups. Ciprofloxacin versus placebo added to cycled and culture-based TNS therapy One trial (296 participants) examined the effect of adding ciprofloxacin versus placebo to cycled and culture-based TNS therapy. There is probably no difference between ciprofloxacin and placebo in eradicating P aeruginosa (OR 0.89, 95% CI 0.55 to 1.44; moderate-certainty evidence). Ciprofloxacin and colistin versus TNS We are uncertain whether there is any difference between groups in eradication of P aeruginosa at up to six months (OR 0.43, 95% CI 0.15 to 1.23; 1 trial, 58 participants) or up to 24 months (OR 0.76, 95% CI 0.24 to 2.42; 1 trial, 47 participants); there was a low rate of short-term eradication in both groups. Ciprofloxacin plus colistin versus ciprofloxacin plus TNS One trial (223 participants) found there may be no difference in positive respiratory cultures at 16 months between ciprofloxacin with colistin versus TNS with ciprofloxacin (OR 1.28, 95% CI 0.72 to 2.29; low-certainty evidence). TNS plus azithromycin compared to TNS plus oral placebo Adding azithromycin may make no difference to the number of participants eradicating P aeruginosa after a three-month treatment phase (risk ratio (RR) 1.01, 95% CI 0.75 to 1.35; 1 trial, 91 participants; low-certainty evidence); there was also no evidence of any difference in the time to recurrence. Ciprofloxacin and colistin versus no treatment A single trial only reported one of our planned outcomes; there were no adverse effects in either group. AZLI for 14 days plus placebo for 14 days compared to AZLI for 28 days We are uncertain whether giving 14 or 28 days of AZLI makes any difference to the proportion of participants having a negative respiratory culture at 28 days (mean difference (MD) -7.50, 95% CI -24.80 to 9.80; 1 trial, 139 participants; very low-certainty evidence). Ceftazidime with IV tobramycin compared with ciprofloxacin (both regimens in conjunction with three months colistin) IV ceftazidime with tobramycin compared with ciprofloxacin may make little or no difference to eradication of P aeruginosa at three months, sustained to 15 months, provided that inhaled antibiotics are also used (RR 0.84, 95 % CI 0.65 to 1.09; P = 0.18; 1 trial, 255 participants; high-certainty evidence). The results do not support using IV antibiotics over oral therapy to eradicate P aeruginosa, based on both eradication rate and financial cost.
AUTHORS' CONCLUSIONS
We found that nebulised antibiotics, alone or with oral antibiotics, were better than no treatment for early infection with P aeruginosa. Eradication may be sustained in the short term. There is insufficient evidence to determine whether these antibiotic strategies decrease mortality or morbidity, improve quality of life, or are associated with adverse effects compared to placebo or standard treatment. Four trials comparing two active treatments have failed to show differences in rates of eradication of P aeruginosa. One large trial showed that intravenous ceftazidime with tobramycin is not superior to oral ciprofloxacin when inhaled antibiotics are also used. There is still insufficient evidence to state which antibiotic strategy should be used for the eradication of early P aeruginosa infection in CF, but there is now evidence that intravenous therapy is not superior to oral antibiotics.
Topics: Child; Child, Preschool; Humans; Infant; Anti-Bacterial Agents; Azithromycin; Ceftazidime; Ciprofloxacin; Colistin; Cystic Fibrosis; Monobactams; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin
PubMed: 37268599
DOI: 10.1002/14651858.CD004197.pub6 -
Clinical Microbiology and Infection :... Jul 2019The aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all...
SCOPE
The aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings.
METHODS
These evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporin-resistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same time-points and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations.
RECOMMENDATIONS
The panel does not recommend routine decolonization of 3GCephRE and CRE carriers. Evidence is currently insufficient to provide recommendations for or against any intervention in patients colonized with AGRE, CoRGNB, CRAB, CRSM, FQRE, PDRGNB and XDRPA. On the basis of the limited evidence of increased risk of CRE infections in immunocompromised carriers, the panel suggests designing high-quality prospective clinical studies to assess the risk of CRE infections in immunocompromised patients. These trials should include monitoring of development of resistance to decolonizing agents during treatment using stool cultures and antimicrobial susceptibility results according to the EUCAST clinical breakpoints.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Europe; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Pseudomonas aeruginosa; Stenotrophomonas maltophilia
PubMed: 30708122
DOI: 10.1016/j.cmi.2019.01.005 -
Journal of Infection and Public Health Mar 2023There is paucity of data describing the impact of COVID-19 pandemic on antimicrobial resistance. This review evaluated the changes in the rate of multidrug resistant... (Review)
Review
BACKGROUND
There is paucity of data describing the impact of COVID-19 pandemic on antimicrobial resistance. This review evaluated the changes in the rate of multidrug resistant gram negative and gram positive bacteria during the COVID-19 pandemic.
METHODS
A search was conducted in PubMed, Science Direct, and Google Scholar databases to identify eligible studies. Studies that reported the impact of COVID-19 pandemic on carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum beta-lactamase inhibitor (ESBL)-producing Enterobacteriaceae, vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Pseudomonas aeruginosa (CPE) were selected. Studies published in English language from the start of COVID-19 pandemic to July 2022 were considered for inclusion.
RESULTS
Thirty eligible studies were selected and most of them were from Italy (n = 8), Turkey (n = 3) and Brazil (n = 3). The results indicated changes in the rate of multidrug resistant bacteria, and the changes varied between the studies. Most studies (54.5%) reported increase in MRSA infection/colonization during the pandemic, and the increase ranged from 4.6 to 170.6%. Five studies (55.6%) reported a 6.8-65.1% increase in VRE infection/colonization during the pandemic. A 2.4-58.2% decrease in ESBL E. coli and a 1.8-13.3% reduction in ESBL Klebsiella pneumoniae was observed during the pandemic. For CRAB, most studies (58.3%) reported 1.5-621.6% increase in infection/colonization during the pandemic. Overall, studies showed increase in the rate of CRE infection/colonization during the pandemic. There was a reduction in carbapenem-resistant E. coli during COVID-19 pandemic, and an increase in carbapenem-resistant K. pneumoniae. Most studies (55.6%) showed 10.4 - 40.9% reduction in the rate of CRPA infection during the pandemic.
CONCLUSION
There is an increase in the rate of multidrug resistant gram positive and gram negative bacteria during the COVID-19 pandemic. However, the rate of ESBL-producing Enterobacteriaceae and CRPA has decrease during the pandemic. Both infection prevention and control strategies and antimicrobial stewardship should be strengthen to address the increasing rate of multidrug resistant gram positive and gram negative bacteria.
Topics: Humans; Anti-Bacterial Agents; Pandemics; Gram-Negative Bacteria; Escherichia coli; Methicillin-Resistant Staphylococcus aureus; Gram-Positive Bacteria; COVID-19; Enterobacteriaceae; Klebsiella pneumoniae; Carbapenems; Microbial Sensitivity Tests
PubMed: 36657243
DOI: 10.1016/j.jiph.2022.12.022 -
Emerging Microbes & Infections Dec 2022Antimicrobial resistance (AMR) and hospital-acquired infections (HAIs) are global health challenges. The burden of antibiotic resistance in HAIs is still unclear in low-... (Meta-Analysis)
Meta-Analysis
Antimicrobial resistance (AMR) and hospital-acquired infections (HAIs) are global health challenges. The burden of antibiotic resistance in HAIs is still unclear in low- and lower-middle-income countries (L-LMICs). This study summarizes recent data on antibiotic resistance in priority HAIs (ESKAPE-E) in L-LMICs and compares them with data from high-income countries (HICs). EMBASE, Web of Science, and Global Index Medicus were searched for studies on AMR patterns in HAIs published from 01/2010 to 10/2020. Random-effects meta-analyses were performed to obtain pooled estimates. In total, 163 eligible studies were included in the review and meta-analysis. The pooled methicillin resistance proportion in was 48.4% (95% confidence interval [95%CI] 41·7-55·2, n = 80). Pooled carbapenem resistance proportions were high in Gram-negative pathogens: : 16·6% (95%CI 10·7-23·4, n = 60); : 34·9% (95%CI 24·6-45·9, n = 50); : 37.1% (95%CI 24·6-45·9, n = 56); spp.: 51·2% (95%CI 27·5-74·7, n = 7); and 72·4% (95%CI 62·1-81·7%, n = 36). A higher resistance proportions were observed for third-generation cephalosporins: : 78·7% (95%CI 71·5-85·2, n = 46); 78·5% (95%CI 72·1-84·2%, n = 58); and spp.: 83·5% (95%CI 71·9-92·8, n = 8). We observed a high between-study heterogeneity (I > 80%), which could not be explained by our set of moderators. Pooled resistance proportions for Gram-negative pathogens were higher in L-LMICs than regional and national estimates from HICs. Patients in resource-constrained regions are particularly affected by AMR. To combat the high resistance to critical antibiotics in L-LMICs, and bridge disparities in health, it is crucial to strengthen local surveillance and the health systems in general.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Developing Countries; Drug Resistance, Bacterial; Hospitals; Humans; Klebsiella pneumoniae
PubMed: 35034585
DOI: 10.1080/22221751.2022.2030196 -
Annals of Medicine and Surgery (2012) Jun 2023Ventilator-associated pneumonia (VAP) is the most common ICU acquired pneumonia among patients who are invasively intubated for mechanical ventilation. Patients with VAP...
Ventilator-associated pneumonia (VAP) is the most common ICU acquired pneumonia among patients who are invasively intubated for mechanical ventilation. Patients with VAP suffer an increased mortality risk, financial burden, and length of stay in the hospital. The authors aimed to review the literature to describe the incidence, mortality, and microbiological evidence of VAP. We selected 13 peer-reviewed articles published from 1 January 2010 to 15 September 2022 from electronic databases for studies among adult or pediatric patients diagnosed with VAP expressed per thousand days admitted in the ICU. The VAP rates ranged from 7 to 43 per thousand days, varying among different countries of the world. A significant rate of mortality was observed in 13 studies ranging from 6.3 to 66.9%. Gram-negative organisms like Acinetobacter spp., Pseudomonas aeruginosa Gram-positive organisms like Staphylococcus aureus were frequently found. Our findings suggest an alarming situation of VAP among patients admitted to the intensive care units with increasing incidence and mortality. The review also found that VAP is more common in males and that there is a significant variation in the incidence and mortality rates of VAP among different countries. The findings of this review can inform the development of infection control and prevention strategies to reduce the burden of VAP. Thus, there is a crucial need for control and preventive measures like interventional studies and educational programs on staff training, hand-hygiene, and the appropriate use of ventilator bundle approach to curb this preventable threat that is increasing at an alarming rate.
PubMed: 37363470
DOI: 10.1097/MS9.0000000000000836 -
Cureus Jun 2022Eculizumab, first-line therapy for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), has infectious side effects in addition to... (Review)
Review
Eculizumab, first-line therapy for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), has infectious side effects in addition to its therapeutic benefits. This study aims to discuss the mechanism of development of infections, prevention, and timely treatment to prevent complications such as septic shock and mortality. The study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist and reporting guidelines for systematic review. Inclusion and exclusion criteria were determined. A total of 10 research papers were extracted after exploring Pubmed and Google Scholar from 2001 to 2021. The New Castle Ottawa Questionnaire for non-randomized clinical trials and the National Institutes of Health (NIH) quality assessment tool for case reports and case series were used to assess the risk of bias. The studies included in this systematic review describe infections with , , unusual species, , and . The main goal of this review is to impress upon the seriousness of the infectious complications associated with eculizumab. Health care providers should maintain a high index of suspicion for early identification and treatment.
PubMed: 35784997
DOI: 10.7759/cureus.25640 -
Microorganisms Dec 2022: Gram-negative bacteria are causative agents of endogenous endophthalmitis (EBE). We aim to systematically review the current literature to assess the aetiologies, risk... (Review)
Review
: Gram-negative bacteria are causative agents of endogenous endophthalmitis (EBE). We aim to systematically review the current literature to assess the aetiologies, risk factors, and early ocular lesions in cases of Gram-negative EBE. : All peer-reviewed articles between January 2002 and August 2022 regarding Gram-negative EBE were included. We conducted a literature search on PubMed and Cochrane Controlled Trials. : A total of 115 studies and 591 patients were included, prevalently Asian (98; 81.7%) and male (302; 62.9%). The most common comorbidity was diabetes (231; 55%). The main aetiologies were (510; 66.1%), (111; 14.4%), and (60; 7.8%). Liver abscesses (266; 54.5%) were the predominant source of infection. The most frequent ocular lesions were vitreal opacity (134; 49.6%) and hypopyon (95; 35.2%). Ceftriaxone (76; 30.9%), fluoroquinolones (14; 14.4%), and ceftazidime (213; 78.0%) were the most widely used as systemic, topical, and intravitreal anti-Gram-negative agents, respectively. The most reported surgical approaches were vitrectomy (130; 24.1%) and evisceration/exenteration (60; 11.1%). Frequently, visual acuity at discharge was no light perception (301; 55.2%). : Gram-negative EBEs are associated with poor outcomes. Our systematic review is mainly based on case reports and case series with significant heterogeneity. The main strength is the large sample spanning over 20 years. Our findings underscore the importance of considering ocular involvement in Gram-negative infections.
PubMed: 36677371
DOI: 10.3390/microorganisms11010080 -
Tropical Medicine & International... Jun 2020Tropical pyomyositis (TP) is a life-threatening bacterial infection of the skeletal muscle that occurs particularly among children, young adults and those with...
Tropical pyomyositis (TP) is a life-threatening bacterial infection of the skeletal muscle that occurs particularly among children, young adults and those with immunocompromised conditions. The appropriate diagnosis and treatment are often delayed due to its non-specific signs, leading to fatal consequences. Staphylococcus aureus, especially methicillin-susceptible S. aureus, is responsible for most TP cases. However, other bacteria (i.e. streptococci, Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Candida spp., Mycobacterium spp.) have been reported. This narrative review provides an update on the epidemiology and clinical course of TP. A special focus is laid on the role of toxins (i.e. Panton-Valentine Leucocidin and α-toxin) in the pathogenesis of TP and their implication for the clinical management of infection.
Topics: Anti-Bacterial Agents; Developing Countries; Exotoxins; Humans; Immunocompromised Host; Pyomyositis; Staphylococcus aureus
PubMed: 32219926
DOI: 10.1111/tmi.13395 -
Antibiotics (Basel, Switzerland) Feb 2023() is among the most common pathogens associated with healthcare-acquired infections, and is often antibiotic resistant, causing significant morbidity and mortality in... (Review)
Review
() is among the most common pathogens associated with healthcare-acquired infections, and is often antibiotic resistant, causing significant morbidity and mortality in cases of bacteremia. It remains unclear how the incidence of bacteremia changed during the Coronavirus Disease 2019 (COVID-19) pandemic, with studies showing almost contradictory conclusions despite enhanced infection control practices during the pandemic. This systematic review sought to examine published reports with incidence rates for bacteremia during (defined as from March 2020 onwards) and prior to the COVID-19 pandemic. A systematic literature search was conducted in accordance with PRISMA guidelines and performed in Cochrane, Embase, and Medline with combinations of the key words (pseudomonas aeruginosa OR PAE) AND (incidence OR surveillance), from database inception until 1 December 2022. Based on the pre-defined inclusion criteria, a total of eight studies were eligible for review. Prior to the pandemic, the prevalence of was on an uptrend. Several international reports found a slight increase in the incidence of bacteremia during the COVID-19 pandemic. These findings collectively highlight the continued importance of good infection prevention and control and antimicrobial stewardship during both pandemic and non-pandemic periods. It is important to implement effective infection prevention and control measures, including ensuring hand hygiene, stepping up environmental cleaning and disinfection efforts, and developing timely guidelines on the appropriate prescription of antibiotics.
PubMed: 36830319
DOI: 10.3390/antibiotics12020409 -
Cureus Jun 2023There has been increased use of cefepime due to concerns about the nephrotoxic effects of the combined use of vancomycin and Zosyn. However, cefepime is associated with... (Review)
Review
There has been increased use of cefepime due to concerns about the nephrotoxic effects of the combined use of vancomycin and Zosyn. However, cefepime is associated with neurotoxicity. We conducted a systematic review using online data to explore the trend of cefepime-induced neurotoxicity over the last 10 years. Forty-six articles met our inclusion criteria, including 73 cases of cefepime-induced neurotoxicity. We noticed a steady increase in the reports of cefepime-induced neurotoxicity, from one case in 2013 to 11 cases in 2022. Individuals aged 65 and older accounted for most cefepime-induced neurotoxicity cases (52%). The top three indications for cefepime administration included bone and joint infections (25%), urinary tract infections (22.7%), and pneumonia (22.7%). Most patients with renal impairment have never had a renal adjustment of their cefepime dosage (either 2 g 12 hours a day or 2 g eight hours a day). Most cases of cefepime-induced neurotoxicity occurred between days two and five (n=29, 71%), while most resolution occurred between days one and five (n=29, 85%). While cefepime continues to be a popularly used and effective antibiotic against gram-negative bacteria like , its dosage needs to be adjusted in patients with renal impairment to avoid neurotoxicity.
PubMed: 37503476
DOI: 10.7759/cureus.40980