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Current Opinion in Critical Care Feb 2022We conducted a systematic literature review to summarize the available evidence regarding the incidence, risk factors, and clinical characteristics of...
PURPOSE OF REVIEW
We conducted a systematic literature review to summarize the available evidence regarding the incidence, risk factors, and clinical characteristics of ventilator-associated pneumonia (VAP) in patients undergoing mechanical ventilation because of acute respiratory distress syndrome secondary to SARS-CoV-2 infection (C-ARDS).
RECENT FINDINGS
Sixteen studies (6484 patients) were identified. Bacterial coinfection was uncommon at baseline (<15%) but a high proportion of patients developed positive bacterial cultures thereafter leading to a VAP diagnosis (range 21-64%, weighted average 50%). Diagnostic criteria varied between studies but most signs of VAP have substantial overlap with the signs of C-ARDS making it difficult to differentiate between bacterial colonization versus superinfection. Most episodes of VAP were associated with Gram-negative bacteria. Occasional cases were also attributed to herpes virus reactivations and pulmonary aspergillosis. Potential factors driving high VAP incidence rates include immunoparalysis, prolonged ventilation, exposure to immunosuppressants, understaffing, lapses in prevention processes, and overdiagnosis.
SUMMARY
Covid-19 patients who require mechanical ventilation for ARDS have a high risk (>50%) of developing VAP, most commonly because of Gram-negative bacteria. Further work is needed to elucidate the disease-specific risk factors for VAP, strategies for prevention, and how best to differentiate between bacterial colonization versus superinfection.
Topics: COVID-19; Humans; Overdiagnosis; Pneumonia, Ventilator-Associated; Respiration, Artificial; Respiratory Distress Syndrome; SARS-CoV-2
PubMed: 34932525
DOI: 10.1097/MCC.0000000000000908 -
International Journal of Infectious... Sep 2021To date, there is no effective treatment for the new coronavirus disease (COVID-19). We aimed to systematically review the literature on the association between the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To date, there is no effective treatment for the new coronavirus disease (COVID-19). We aimed to systematically review the literature on the association between the combination of tocilizumab (TCZ) and systemic corticosteroid therapy (SCT) on outcomes of COVID-19 patients.
METHODS
We searched MEDLINE, Cochrane Central, and preprints, for studies in which health outcomes were compared between adults with severe COVID-19 who received TCZ and SCT and those who received standard of care without TCZ. Record screening, data extraction, and risk of bias assessment were performed in duplicate. Random effect models were used when pooling crude numbers and adjusted effect estimates of study outcomes.
RESULTS
Our search identified seventeen studies. The pooled crude mortality rate was lower in the combination arm (relative risk, RR=0.62, 95% confidence interval [CI]=0.42 - 0.91; I=60%). The adjusted mortality rates were also lower in the combination arm (RR=0.58, 95% CI=0.42 - 0.81; I=71%). The rate of superinfections did not differ between the two interventions.
CONCLUSIONS
The findings of this study show that combination of TCZ and SCT compared to SOC has lower mortality rates. There is an urgent need for well-designed randomized trials to assess the safety and efficacy of this combination in subjects with severe COVID-19.
Topics: Adrenal Cortex Hormones; Adult; Antibodies, Monoclonal, Humanized; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34273515
DOI: 10.1016/j.ijid.2021.07.021 -
The Journal of Antimicrobial... Jan 2015Data on the relative efficacy of β-lactam/β-lactamase inhibitors (BL/BLIs) versus carbapenems are scant. (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Data on the relative efficacy of β-lactam/β-lactamase inhibitors (BL/BLIs) versus carbapenems are scant.
METHODS
This is a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing any BL/BLI versus any carbapenem for the treatment of sepsis. The primary outcome was all-cause mortality. A broad search was conducted with no restrictions on language, publication status or date. Two reviewers independently applied the inclusion criteria and extracted the data. Assessment of risk of bias was performed using the domain-based approach. Subgroup analyses were used to investigate heterogeneity and focus on patient groups more likely to harbour ESBL-positive bacteria. Risk ratios (RRs) with 95% CIs were calculated and pooled.
RESULTS
Thirty-one RCTs were included. There was no difference between BL/BLIs and carbapenems in terms of mortality (RR 0.98, 95% CI 0.79-1.20), without heterogeneity. No differences were observed with regard to clinical or microbiological failure and bacterial superinfections. The results were not affected by risk of bias. No differences were detected in the subgroups of patients with nosocomial infections, Gram-negative infections and neutropenic fever. Adverse events requiring discontinuation were more common with BL/BLIs, on account of an increased incidence of diarrhoea. However, Clostridium difficile-associated diarrhoea (RR 0.29, 95% CI 0.10-0.87) was more frequent with carbapenems and seizures were more frequent with imipenem (RR 0.21, 95% CI 0.05-0.93).
CONCLUSIONS
No differences in efficacy between BL/BLIs and carbapenems exist in RCTs including patient populations with a certain, albeit unknown, rate of ESBL-positive bacteria causing infections.
Topics: Bacterial Infections; Clostridioides difficile; Diarrhea; Humans; Randomized Controlled Trials as Topic; Sepsis; Survival Analysis; Treatment Outcome; beta-Lactamase Inhibitors; beta-Lactams
PubMed: 25261419
DOI: 10.1093/jac/dku351 -
Mycoses Oct 2021Chronic pulmonary aspergillosis (CPA) is an emerging fungal infectious disease of public health importance. We conducted a systematic review of studies reporting the... (Review)
Review
Chronic pulmonary aspergillosis (CPA) is an emerging fungal infectious disease of public health importance. We conducted a systematic review of studies reporting the outcomes of patients with CPA managed surgically in Africa. A search of Medline, Embase, Web of Science, Google Scholar and African Journals Online was conducted to identify studies indexed from inception to June 2021 that examined surgical management of CPA in Africa. All articles that presented primary data, including case reports and case series, were included. We excluded review articles. A total of 891 cases (557 males (62.5%), mean age 39.3 years) extracted from 27 eligible studies published between 1976 and 2020 from 11 African countries were included. Morocco (524, 59%) and Senegal (99, 11%) contributed the majority of cases. Active or previous pulmonary tuberculosis was reported in 677 (76.0%) cases. Haemoptysis was reported in 682 (76.5%) cases. Lobectomy (either unilateral or bilateral, n = 493, 55.3%), pneumonectomy (n = 154, 17.3%) and segmentectomy (n = 117, 13.1%) were the most frequently performed surgical procedures. Thirty (4.9%) cases from South Africa received bronchial artery embolisation. Empyema (n = 59, 27.4%), significant haemorrhage (n = 38, 173.7%), incomplete lung expansion (n = 26, 12.1%) and prolonged air leak (n = 24, 11.2%) were the most frequent complications. Overall, 45 (5.1%) patients died. The causes of death included respiratory failure (n = 14), bacterial superinfection/sepsis (n = 10), severe haemorrhage (n = 5), cardiopulmonary arrest (n = 3) and complications of chronic obstructive pulmonary disease (n = 3). The cause of death was either unknown or unspecified in 9 cases. We conclude that surgical treatment had very low mortality rates and maybe considered as first-line management option in centres with experience and expertise in Africa.
Topics: Africa; Hemoptysis; Humans; Pneumonectomy; Pulmonary Aspergillosis; Retrospective Studies
PubMed: 34363630
DOI: 10.1111/myc.13359 -
Hand Surgery & Rehabilitation Apr 2024The nail unit is the most commonly affected area in hand infections, which can be primary infection or superinfection complicating other nail or skin disorders. Trauma,... (Review)
Review
The nail unit is the most commonly affected area in hand infections, which can be primary infection or superinfection complicating other nail or skin disorders. Trauma, mechanical or chemical, is usually the trigger enabling infiltration of infectious organisms. Artificial nails and nail polish are also a possible cause of bacterial infection, harboring microorganisms. In severe acute bacterial infection, surgical intervention is often needed to prevent morbidity and disability. Abscess should always be drained, but viral infection such as herpetic whitlow, may mimic an abscess and, in contrast, requires non-operative treatment; to prevent sequelae. A more conservative approach is also generally advisable in less severe bacterial infection, other viral infections and in subacute or chronic nail infection. The present review deals with acute, subacute and chronic bacterial and viral infections of the nail unit, with a focus on diagnostic and treatment options. LEVEL OF EVIDENCE: III, systematic review of level III studies.
Topics: Humans; Nail Diseases; Virus Diseases; Anti-Bacterial Agents; Bacterial Infections
PubMed: 36427761
DOI: 10.1016/j.hansur.2022.11.006 -
Critical Care Medicine Apr 2024This systematic review and Bayesian network meta-analysis evaluated the efficacy and safety of hydrocortisone combined with fludrocortisone or hydrocortisone alone,... (Meta-Analysis)
Meta-Analysis
Do We Need to Administer Fludrocortisone in Addition to Hydrocortisone in Adult Patients With Septic Shock? An Updated Systematic Review With Bayesian Network Meta-Analysis of Randomized Controlled Trials and an Observational Study With Target Trial Emulation.
OBJECTIVES
This systematic review and Bayesian network meta-analysis evaluated the efficacy and safety of hydrocortisone combined with fludrocortisone or hydrocortisone alone, compared with placebo in adult patients with septic shock.
DATA SOURCES
By extending a prior Cochrane review, databases, including PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov , along with other relevant websites, were searched until August 31, 2023.
STUDY SELECTION
Randomized controlled trials (RCTs) and observational studies using target trial emulation were included.
DATA EXTRACTION
The primary outcome was short-term mortality with an emphasis on 28- or 30-day mortality as the main measure and in-hospital or ICU mortality as the nearest surrogate of this measure. Three of the most common adverse events, namely, gastroduodenal bleeding, superinfection, and hyperglycemia, were also considered.
DATA SYNTHESIS
A total of 19 studies involving 95,841 patients were included. Hydrocortisone plus fludrocortisone showed the lowest short-term mortality versus placebo (odds ratio [OR]: 0.79; 95% credible interval [CrI], 0.64-0.99; number needed to treat [NNT]: 21, range: 12-500; low certainty of evidence) in terms of informative priors. The surface under the cumulative ranking curve values for hydrocortisone plus fludrocortisone, hydrocortisone alone, and placebo were 0.9469, 0.4542, and 0.0989, respectively. Consistent results were observed in RCTs alone and those using a daily 200-mg dose of hydrocortisone. Although gastroduodenal bleeding or superinfection showed no clear increase, hyperglycemia risk increased. The ORs were 0.53 for placebo versus hydrocortisone plus fludrocortisone and 0.64 for placebo versus hydrocortisone alone, with very low certainty of evidence.
CONCLUSIONS
In adults with septic shock, hydrocortisone plus fludrocortisone improved short-term survival with minimal adverse events compared with hydrocortisone alone or placebo. However, these findings are not definitive due to the limited certainty of evidence and wide NNT range. Additional large-scale, placebo-controlled RCTs are needed to provide conclusive evidence.
Topics: Adult; Humans; Hydrocortisone; Fludrocortisone; Shock, Septic; Network Meta-Analysis; Superinfection; Randomized Controlled Trials as Topic; Hyperglycemia; Observational Studies as Topic
PubMed: 38156911
DOI: 10.1097/CCM.0000000000006161 -
Clinical Microbiology and Infection :... Aug 2022A significant increased risk of complications and mortality in immunocompromised patients affected by COVID-19 has been described. However, the impact of COVID-19 in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A significant increased risk of complications and mortality in immunocompromised patients affected by COVID-19 has been described. However, the impact of COVID-19 in solid organ transplant (SOT) recipients is an issue still under debate, due to conflicting evidence that has emerged from different observational studies.
OBJECTIVES
We performed a systematic review with a meta-analysis to assess the clinical outcome in SOT recipients with COVID-19 compared with the general population.
DATA SOURCES
PubMed-MEDLINE and Scopus were independently searched until 13 October 2021.
STUDY ELIGIBILITY CRITERIA
Prospective or retrospective observational studies comparing clinical outcome in SOT recipients versus general populations affected by COVID-19 were included. The primary endpoint was 30-day mortality.
PARTICIPANTS
Participants were patients with confirmed COVID-19.
INTERVENTIONS
Interventions reviewed were SOTs.
METHODS
The quality of the included studies was independently assessed with the Risk of Bias in Non-randomized Studies of Interventions tool for observational studies. The meta-analysis was performed by pooling ORs retrieved from studies providing adjustment for confounders using a random-effects model with the inverse variance method. Multiple subgroups and sensitivity analyses were conducted to investigate the source of heterogeneity.
RESULTS
A total of 3501 articles were screened, and 31 observational studies (N = 590 375; 5759 SOT recipients vs. 584 616 general population) were included in the meta-analyses. No difference in 30-day mortality rate was found in the primary analysis, including studies providing adjustment for confounders (N = 17; 3752 SOT recipients vs. 159 745 general population; OR: 1.13; 95% CI, 0.94-1.35; I = 33.9%). No evidence of publication bias was reported. A higher risk of intensive care unit admission (OR: 1.56; 95% CI, 1.03-2.63) and occurrence of acute kidney injury (OR: 2.50; 95% CI, 1.81-3.45) was found in SOT recipients.
CONCLUSIONS
No increased risk in mortality was found in SOT recipients affected by COVID-19 compared with the general population when adjusted for demographic and clinical features and COVID-19 severity.
Topics: COVID-19; Humans; Organ Transplantation; Prospective Studies; Retrospective Studies; Transplant Recipients
PubMed: 35289294
DOI: 10.1016/j.cmi.2022.02.039 -
Revista Brasileira de Terapia Intensiva 2021The Sociedade Portuguesa de Cuidados Intensivos and the Infection and Sepsis Group have previously issued health service and management recommendations for critically...
Update of the recommendations of the Sociedade Portuguesa de Cuidados Intensivos and the Infection and Sepsis Group for the approach to COVID-19 in Intensive Care Medicine.
INTRODUCTION
The Sociedade Portuguesa de Cuidados Intensivos and the Infection and Sepsis Group have previously issued health service and management recommendations for critically ill patients with COVID-19. Due to the evolution of knowledge, the panel of experts was again convened to review the current evidence and issue updated recommendations.
METHODS
A national panel of experts who declared that they had no conflicts of interest regarding the development of the recommendations was assembled. Operational questions were developed based on the PICO methodology, and a rapid systematic review was conducted by consulting different bibliographic sources. The panel determined the direction and strength of the recommendations using two Delphi rounds, conducted in accordance with the principles of the GRADE system. A strong recommendation received the wording "is recommended", and a weak recommendation was written as "is suggested."
RESULTS
A total of 48 recommendations and 30 suggestions were issued, covering the following topics: diagnosis of SARS-CoV-2 infection, coinfection and superinfection; criteria for admission, cure and suspension of isolation; organization of services; personal protective equipment; and respiratory support and other specific therapies (antivirals, immunomodulators and anticoagulation).
CONCLUSION
These recommendations, specifically oriented to the Portuguese reality but that may also apply to Portuguese-speaking African countries and East Timor, aim to support health professionals in the management of critically ill patients with COVID-19. They will be continuously reviewed to reflect the progress of our understanding and the treatment of this pathology.
Topics: COVID-19; Critical Care; Humans; Intensive Care Units; SARS-CoV-2; Sepsis
PubMed: 35081236
DOI: 10.5935/0103-507X.0103-507X-rbti-20210080 -
The Lancet. Microbe Feb 2023HIV-1 infections initiated by multiple founder variants are characterised by a higher viral load and a worse clinical prognosis than those initiated with single founder... (Meta-Analysis)
Meta-Analysis
BACKGROUND
HIV-1 infections initiated by multiple founder variants are characterised by a higher viral load and a worse clinical prognosis than those initiated with single founder variants, yet little is known about the routes of exposure through which transmission of multiple founder variants is most probable. Here we used individual patient data to calculate the probability of multiple founders stratified by route of HIV exposure and study methodology.
METHODS
We conducted a systematic review and meta-analysis of studies that estimated founder variant multiplicity in HIV-1 infection, searching MEDLINE, Embase, and Global Health databases for papers published between Jan 1, 1990, and Sept 14, 2020. Eligible studies must have reported original estimates of founder variant multiplicity in people with acute or early HIV-1 infections, have clearly detailed the methods used, and reported the route of exposure. Studies were excluded if they reported data concerning people living with HIV-1 who had known or suspected superinfection, who were documented as having received pre-exposure prophylaxis, or if the transmitting partner was known to be receiving antiretroviral treatment. Individual patient data were collated from all studies, with authors contacted if these data were not publicly available. We applied logistic meta-regression to these data to estimate the probability that an HIV infection is initiated by multiple founder variants. We calculated a pooled estimate using a random effects model, subsequently stratifying this estimate across exposure routes in a univariable analysis. We then extended our model to adjust for different study methods in a multivariable analysis, recalculating estimates across the exposure routes. This study is registered with PROSPERO, CRD42020202672.
FINDINGS
We included 70 publications in our analysis, comprising 1657 individual patients. Our pooled estimate of the probability that an infection is initiated by multiple founder variants was 0·25 (95% CI 0·21-0·29), with moderate heterogeneity (Q=132·3, p<0·0001, I=64·2%). Our multivariable analysis uncovered differences in the probability of multiple variant infection by exposure route. Relative to a baseline of male-to-female transmission, the predicted probability for female-to-male multiple variant transmission was significantly lower at 0·13 (95% CI 0·08-0·20), and the probabilities were significantly higher for transmissions in people who inject drugs (0·37 [0·24-0·53]) and men who have sex with men (0·30 [0·33-0·40]). There was no significant difference in the probability of multiple variant transmission between male-to-female transmission (0·21 [0·14-0·31]), post-partum transmission (0·18 [0·03-0·57]), pre-partum transmission (0·17 [0·08-0·33]), and intra-partum transmission (0·27 [0·14-0·45]).
INTERPRETATION
We identified that transmissions in people who inject drugs and men who have sex with men are significantly more likely to result in an infection initiated by multiple founder variants, and female-to-male infections are significantly less probable. Quantifying how the routes of HIV infection affect the transmission of multiple variants allows us to better understand how the evolution and epidemiology of HIV-1 determine clinical outcomes.
FUNDING
Medical Research Council Precision Medicine Doctoral Training Programme and a European Research Council Starting Grant.
Topics: Humans; Male; Female; HIV Infections; HIV-1; Homosexuality, Male; Sexual and Gender Minorities; Anti-HIV Agents; HIV Seropositivity
PubMed: 36642083
DOI: 10.1016/S2666-5247(22)00327-5 -
BioMed Research International 2019To reevaluate the benefits and risks of corticosteroid treatment in adult patients with septic shock. This study was performed based on PRISMA guidelines. Randomized... (Meta-Analysis)
Meta-Analysis
To reevaluate the benefits and risks of corticosteroid treatment in adult patients with septic shock. This study was performed based on PRISMA guidelines. Randomized controlled trials (RCTs) of corticosteroids versus placebo were retrieved from PubMed, MEDLINE, EMBASE, Web of Science, the Cochrane Central RCTs, and ClinicalTrials.gov from January 1980 to April 2018. We also conducted a trial sequential analysis to indicate the possibility of type I or II errors and calculate the information size. Grading of Recommendations, Assessment, Development and Evaluation approach (GRADE) was applying to assess the certainty of evidence at the primary outcome level. Twenty-one RCTs were identified and analyzed. Patients treated with corticosteroid had a 7% reduction in relative risk in 28-day all-cause mortality compared to controls (RR 0.93, 95% CI 0.88 to 0.99). However, there were no significant differences for the intensive care unit (ICU) mortality (RR 0.97, 95% CI 0.86 to 1.09) or in-hospital mortality (RR 1.01, 95% CI 0.92 to 1.11). Corticosteroids shortened the length of ICU stay by 1.04 days (RR -1.04, 95% CI -1.72 to -0.36) and the length of hospital stay by 2.49 days (RR -2.49, 95% CI -4.96 to -0.02). Corticosteroids increased the risk of hyperglycemia (RR 1.11, 95% CI 1.06 to 1.16) but not gastroduodenal bleeding (RR 1.06, 95% CI 0.82 to 1.37) or superinfection (RR 1.04, 95% CI 0.94 to 1.15). However, some date on secondary outcomes were unavailable because they were not measured or not reported in the included studies which may cause a lack of power or selective outcome reporting. The information size was calculated at 10044 patients. Trial sequential analysis showed that the meta-analysis was conclusive and the risk of type 2 error was minimal. Corticosteroids are likely to be effective in reducing 28-day mortality and attenuating septic shock without increasing the rate of life-threatening complications. TSA showed that the risk of type II error in this meta-analysis was minimal and the result was conclusive.
Topics: Adrenal Cortex Hormones; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Publication Bias; Randomized Controlled Trials as Topic; Respiration, Artificial; Risk Factors; Shock, Septic
PubMed: 31281831
DOI: 10.1155/2019/3175047