Severe infections in critically ill solid organ transplant recipients

BackgroundSevere infections are among the most common causes of death in immunocompromised patients admitted to the intensive care unit. The epidemiology, diagnosis and treatment of these infections has evolved in the last decade.AimsWe aim to provide a comprehensive review of these severe infections in this population.SourcesReview of the literature pertaining to severe infections in critically ill solid organ transplant recipients. PubMed and Embase databases were searched for documents published since database inception until November 2017.ContentThe epidemiology of severe infections has changed in the immunocompromised patients. This population is presenting to the intensive care unit with specific transplantation procedure–related infections, device-associated infections, a multitude of opportunistic viral infections, an increasing number of nosocomial infections and bacterial diseases with a more limited therapeutic armamentarium. Both molecular diagnostics and imaging techniques have had substantial progress in the last decade, which will, we hope, translate into faster and more precise diagnoses, as well as more optimal empirical treatment de-escalation.ImplicationsThe key clinical elements to improve the outcome of critically ill solid organ transplant recipients depend on the knowledge of geographic epidemiology, specific surgical procedures, net state of immunosuppression, hospital microbial ecology, aggressive diagnostic strategy and search for source control, rapid initiation of antimicrobials and minimization of iatrogenic immunosuppression.     

Cost-effectiveness of genome sequencing for diagnosing patients with undiagnosed rare genetic diseases

PurposeTo estimate the cost-effectiveness of genome sequencing (GS) for diagnosing critically ill infants and noncritically ill pediatric patients (children) with suspected rare genetic diseases from a United States health sector perspective.MethodsA decision-analytic model was developed to simulate the diagnostic trajectory of patients. Parameter estimates were derived from a targeted literature review and meta-analysis. The model simulated clinical and economic outcomes associated with 3 diagnostic pathways: (1) standard diagnostic care, (2) GS, and (3) standard diagnostic care followed by GS.ResultsFor children, costs of GS ($7284) were similar to that of standard care ($7355) and lower than that of standard care followed by GS pathways ($12,030). In critically ill infants, when cost estimates were based on the length of stay in the neonatal intensive care unit, the lowest cost pathway was GS ($209,472). When only diagnostic test costs were included, the cost per diagnosis was $17,940 for standard, $17,019 for GS, and $20,255 for standard care followed by GS.ConclusionThe results of this economic model suggest that GS may be cost neutral or possibly cost saving as a first line diagnostic tool for children and critically ill infants.     

Use of biomarkers to individualize antimicrobial therapy duration: a narrative review

BackgroundReducing the overuse of antimicrobials is imperative for the sake of minimizing antimicrobial-associated adverse effects, optimizing resource utilization, and curtailing the rise in multidrug-resistant organisms. Biomarkers reflect the host responses to infection and may assist with minimizing unnecessary antimicrobial usage.ObjectivesTo review the literature pertaining to the performance of biomarkers specifically used to guide the duration of antimicrobial therapy (AMT).SourcesRandomized controlled trials, observational studies, and meta-analyses assessing biomarker-guided approaches to AMT decision-making and their impact on the duration of therapy were reviewed.ContentSeveral randomized controlled trials and real-world observational studies have shown that a procalcitonin (PCT)-guided strategy can help clinicians individualize the duration of AMT, particularly among non–critically ill patients hospitalized with suspected respiratory tract infections when using a PCT cut-off value of <0.25 μg/L and critically ill patients with respiratory tract infections or undifferentiated sepsis when using a PCT cut-off value of <0.5 μg/L or ≥80% decline in the peak level. C-reactive protein is a non-specific marker of inflammation that may also assist with an early discontinuation of AMT; however, data are limited. Haematological biomarkers are prone to variance between individuals and are often influenced by medications and non-infectious conditions, making them less reliable for the purposes of AMT decision-making. Novel biomarkers such as multi-protein signatures and host gene expression tests have shown promise as tools to better differentiate between bacterial and non-bacterial infections; clinical studies are needed to determine whether they can be used to help optimize the duration of AMT.ImplicationsStudies have demonstrated that a PCT-guided strategy, when utilized appropriately, can help guide clinicians to individualize and often reduce the duration of AMT, especially in patients hospitalized with respiratory tract infections and those admitted to the intensive care unit with suspected respiratory tract infections or sepsis. The impact of utilizing other biomarkers is less clear and requires further study.     

Management of KPC-producing Klebsiella pneumoniae infections

BackgroundKlebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has become one of the most important contemporary pathogens, especially in endemic areas.AimsTo provide practical suggestion for physicians dealing with the management of KPC-KP infections in critically ill patients, based on expert opinions.SourcesPubMed search for relevant publications related to the management of KPC-KP infections.ContentsA panel of experts developed a list of 12 questions to be addressed. In view of the current lack of high-level evidence, they were asked to provide answers on the bases of their knowledge and experience in the field. The panel identified several key aspects to be addressed when dealing with KPC-KP in critically ill patients (preventing colonization in the patient, preventing infection in the colonized patient and colonization of his or her contacts, reducing mortality in the infected patient by rapidly diagnosing the causative agent and promptly adopting the best therapeutic strategy) and provided related suggestions that were based on the available observational literature and the experience of panel members.ImplicationsDiagnostic technologies could speed up the diagnosis of KPC-KP infections. Combination treatment should be preferred to monotherapy in cases of severe infections. For non–critically ill patients without severe infections, results from randomized clinical trials are needed for ultimately weighing benefits and costs of using combinations rather than monotherapy. Multifaceted infection control interventions are needed to decrease the rates of colonization and cross-transmission of KPC-KP.     

Clinical microbiology in the intensive care unit: Strategic and operational characteristics

Infection is a major cause of morbidity and mortality among patients admitted in intensive care units (ICUs). The application of the principles and the practice of Clinical Microbiology for ICU patients can significantly improve clinical outcome. The present article is aimed at summarising the strategic and operational characteristics of this unique field where medical microbiology attempts to venture into the domain of direct clinical care of critically ill patients. The close and strategic partnership between clinical microbiologists and intensive care specialists, which is essential for this model of patient care have been emphasized. The article includes discussions on a variety of common clinical-microbiological problems faced in the ICUs such as ventilator-associated pneumonia, blood stream infections, skin and soft tissue infection, UTI, infection control, besides antibiotic management.     

Complications and benefits of intrahospital transport of adult Intensive Care Unit patients

Background:The transport of critically ill patients for procedures or tests outside the Intensive Care Unit (ICU) is potentially hazardous; hence, the transport process must be organized and efficient. Plenty of data is available on pre- and inter-hospital transport of patients; the data on intrahospital transport of patients are limited. We audited the complications and benefits of intrahospital transport of critically ill patients in our tertiary care center over 6 months.Results:Among the 120 adult patients, 5 (4.1%) required endotracheal intubation, 5 (4.1%) required intercostal drain placement, and 20 (16.7%) required cardiopulmonary resuscitation (CPR). Dislodgement of central venous catheter occurred in 2 (1.6%) patients, drain came out in 3 (2.5%) patients, orogastric tube came out in 1 (0.8%) patient, 2 (1.6%) patients self-extubated, and in one patient, tracheostomy tube was dislodged. The adverse events were more in patients who spent more than 60 min outside the ICU, particularly requirement of CPR (18 [25%] vs. 2 [4.2%], ≤60 min vs. >60 min, respectively) with P < 0.05. Transport led to change in therapy in 32 (26.7%) patients.Conclusion:Transport in critically ill cancer patients is more hazardous and needs adequate pretransport preparations. Transport in spite being hazardous may lead to a beneficial change in therapy in a significant number of patients.Key words: Complications, critically ill, intrahospital transport     

The effect of rapid exome sequencing on downstream health care utilization for infants with suspected genetic disorders in an intensive care unit

PurposeThis study aimed to compare downstream utilization of medical services among critically ill infants admitted to intensive care units who received rapid exome sequencing (ES) and those who followed alternative diagnostic testing pathways.MethodsUsing propensity score–weighted regression models including sex, age at admission, and severity indicators, we compared a group of 47 infants who underwent rapid ES with a group of 211 infants who did not receive rapid ES. Utilization and cost indicators were compared between cohorts using negative binomial models for utilization and two-part models for costs.ResultsAfter controlling for patients’ sociodemographic and clinical characteristics, we found no statistically significant difference in outpatient visits, hospitalizations, intensive care unit or total length of stay, or length of stay–associated costs between the cohorts at 12- or 26-month follow-up. Similarly, there was no evidence of higher utilization or costs by the ES group when infants who died were removed from the analysis.ConclusionWhen examining utilization during and beyond the diagnostic trajectory, there is no evidence that ES changes frequency of outpatient visits or use of in-hospital resources in critically ill infants with suspected genetic disorders.     

Patient involvement in micro-decisions in intensive care

ObjectiveThe objective of this study was to explore how bedside micro-decisions were made between conscious patients on mechanical ventilation in intensive care and their healthcare providers.MethodsUsing video recordings to collect data, we explored micro-decisions between 10 mechanically ventilated patients and 60 providers in interactions at the bedside. We first identified the types of micro-decisions before using an interpretative approach to analyze the decision-making processes and create prominent themes.ResultsWe identified six types of bedside micro-decisions; non-invited, substituted, guided, invited, shared and self-determined decisions. Three themes were identified in the decision-making processes: 1) being an observer versus a participant in treatment and care, 2) negotiating decisions about individualized care (such as tracheal suctioning or medication),and 3) balancing empowering activities with the need for energy restoration.ConclusionThis study revealed that bedside decision-making processes in intensive care were characterized by a high degree of variability between and within patients. Communication barriers influenced patients’ ability to express their preferences. An increased understanding of how micro-decisions occur with non-vocal patients is needed to strengthen patient participation.Practice ImplicationsWe advise providers to make an effort to solicit patients’ preferences when caring for critically ill patients.     

Efficacy and safety of antiviral therapy in critically ill patients with mechanical ventilation: a meta-analysis with trial sequential analysis of randomized controlled trials

ObjectivesViral reactivation is frequently detected in critically ill patients undergoing mechanical ventilation and is associated with worse outcomes. However, the efficacy and safety of antiviral therapy in these patients remain unknown. This review aims to assess the effects of antiviral therapy on mortality, viral reactivation, and adverse events in critically ill patients undergoing mechanical ventilation.MethodsData sources were Medline, Embase, the Cochrane Library, and reference lists. The study included randomized controlled trials that compared antiviral therapy with placebo, standard care, or no treatment. Participants were critically ill patients undergoing mechanical ventilation. Intervention was antiviral therapy. Assessment of risk of bias used the Cochrane risk of bias tool. For methods of data synthesis, risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model for meta-analysis with trial sequential analysis.ResultsNine trials with a broad spectrum of critically ill patients were included. No association was found between antiviral therapy and all-cause mortality at the longest follow-up (nine trials, 1790 patients, RR 0.93, 95%CI 0.79–1.11, I² 3%). Trial sequential analysis showed that the cumulative Z curve crossed the futility boundary establishing sufficient evidence. No association was also found between antiviral therapy and 28-day mortality, in-hospital mortality, 60-day mortality, or 90-day mortality. However, antiviral therapy was associated with a reduction in viral reactivation (five trials, 644 patients, RR 0.23, 95%CI 0.14–0.37, I² 0%). Trial sequential analysis showed that the cumulative Z curve crossed the trial sequential monitoring boundary for benefit establishing sufficient evidence. Antiviral therapy was not associated with an increased risk of renal insufficiency (eight trials, 1574 patients, RR 0.88, 95%CI 0.73–1.05, I² 0%).ConclusionsNo association between antiviral therapy and mortality was found, but antiviral therapy reduced viral reactivation without increasing the risk of renal insufficiency in critically ill patients with mechanical ventilation.     

Occurrence,presentation and treatment of candidemia

Candida is one of the most common causes of nosocomial bloodstream infections. Candidemia is not confined to hematological patients, intensive care units or abdominal surgery wards, but it is remarkably frequent in the internal medicine setting. High mortality associated with candidemia can be reduced by prompt, appropriate antifungal therapy. The epidemiology of species has been shifting toward non-albicans strains. Significant improvements in nonculture-based diagnostic methods, such as serological markers, have been made in recent years, and novel diagnostic techniques should be further studied to enable early pre-emptive therapy. Treatment guidelines indicate that echinocandins are at present the best choice for patients who are severely ill or possibly infected with fluconazole-resistant strains.     

Colistin treatment in patients with ICU-acquired infections caused by multiresistant Gram-negative bacteria: the renaissance of an old antibiotic

A retrospective case series study was performed in a 30-bed general intensive care unit (ICU) of a tertiary care hospital to assess the effectiveness and safety of colistin in 43 critically ill patients with ICU-acquired infections caused by multiresistant Gram-negative bacteria. Various ICU-acquired infections, mainly pneumonia and bacteraemia caused by multiresistant strains of Pseudomonas aeruginosa and/or Acinetobacter baumannii, were treated with colistin. Good clinical response (cure or improvement) was noted in 74.4% of patients. Deterioration of renal function occurred in 18.6% of patients during colistin therapy. Nephrotoxicity was elevated significantly in those patients with a history of renal failure (62.5%). All-cause mortality amounted to 27.9%. In this group of critically ill patients, an age of >50 years (OR, 5.4; 95% CI 1.3-24.9) and acute renal failure (OR, 8.2; 95% CI 2.9-23.8) were independent predictors of mortality. Colistin should be considered as a treatment option in critically ill patients with infection caused by multiresistant Gram-negative bacilli.     

Clinical course and outcomes of critically ill patients with COVID-19 infection: a systematic review

ObjectivesCoronavirus disease 19 (COVID-19) is a major cause of hospital admission and represents a challenge for patient management during intensive care unit (ICU) stay. We aimed to describe the clinical course and outcomes of COVID-19 pneumonia in critically ill patients.MethodsWe performed a systematic search of peer-reviewed publications in MEDLINE, EMBASE and the Cochrane Library up to 15th August 2020. Preprints and reports were also included if they met the inclusion criteria. Study eligibility criteria were full-text prospective, retrospective or registry-based publications describing outcomes in patients admitted to the ICU for COVID-19, using a validated test. Participants were critically ill patients admitted in the ICU with COVID-19 infection.ResultsFrom 32 articles included, a total of 69 093 patients were admitted to the ICU and were evaluated. Most patients included in the studies were male (76 165/128 168, 59%, 26 studies) and the mean patient age was 56 (95%CI 48.5–59.8) years. Studies described high ICU mortality (21 145/65 383, 32.3%, 15 studies). The median length of ICU stay was 9.0 (95%CI 6.5–11.2) days, described in five studies. More than half the patients admitted to the ICU required mechanical ventilation (31 213/53 465, 58%, 23 studies) and among them mortality was very high (27 972/47 632, 59%, six studies). The duration of mechanical ventilation was 8.4 (95%CI 1.6–13.7) days. The main interventions described were the use of non-invasive ventilation, extracorporeal membrane oxygenation, renal replacement therapy and vasopressors.ConclusionsThis systematic review, including approximately 69 000 ICU patients, demonstrates that COVID-19 infection in critically ill patients is associated with great need for life-sustaining interventions, high mortality, and prolonged length of ICU stay.     

Management of infected pancreatic necrosis in the intensive care unit: a narrative review

BackgroundSevere acute pancreatitis is marked by organ failure and (peri)pancreatic necrosis with local complications such as infected necrosis. Infection of these necrotic collections together with organ failure remain the major causes of admission to an intensive care unit (ICU) in acute pancreatitis. Appropriate treatment of infected necrosis is essential to reduce morbidity and mortality. Overall knowledge of the treatment options within a multidisciplinary team—with special attention to the appropriate use of antimicrobial therapy and invasive treatment techniques for source control—is essential in the treatment of this complex disease.ObjectivesTo address the current state of microbiological diagnosis, antimicrobial treatment, and source control for infected pancreatic necrosis in the ICU.SourcesA literature search was performed using the Medline and Cochrane libraries for articles subsequent to 2003 using the keywords: infected necrosis, pancreatitis, intensive care medicine, treatment, diagnosis and antibiotic(s).ContentThis narrative review provides an overview of key elements of diagnosis and treatment of infected pancreatic necrosis in the ICU.ImplicationsIn pancreatic necrosis it is essential to continuously (re)evaluate the indication for antimicrobial treatment and invasive source control. Invasive diagnostics (e.g. through fine-needle aspiration, FNA), preferably prior to the start of broad-spectrum antimicrobial therapy, is advocated. Antimicrobial stewardship principles apply: paying attention to altered pharmacokinetics in the critically ill, de-escalation of broad-spectrum therapy once cultures become available, and early withdrawal of antibiotics once source control has been established. This is important to prevent the development of antimicrobial resistance, especially in a group of patients who may require repeated courses of antibiotics during the prolonged course of their illness.     

Prospective,phenotype-driven selection of critically ill neonates for rapid exome sequencing is associated with high diagnostic yield

PurposeTo investigate the impact of rapid-turnaround exome sequencing in critically ill neonates using phenotype-based subject selection criteria.MethodsIntensive care unit babies aged <6 months with hypotonia, seizures, a complex metabolic phenotype, and/or multiple congenital malformations were prospectively enrolled for rapid (<7 day) trio-based exome sequencing. Genomic variants relevant to the presenting phenotype were returned to the medical team.ResultsA genetic diagnosis was attained in 29 of 50 (58%) sequenced cases. Twenty-seven (54%) patients received a molecular diagnosis involving known disease genes; two additional cases (4%) were solved with pathogenic variants found in novel disease genes. In 24 of the solved cases, diagnosis had impact on patient management and/or family members. Management changes included shift to palliative care, medication changes, involvement of additional specialties, and the consideration of new experimental therapies.ConclusionPhenotype-based patient selection is effective at identifying critically ill neonates with a high likelihood of receiving a molecular diagnosis via rapid-turnaround exome sequencing, leading to faster and more accurate diagnoses, reducing unnecessary testing and procedures, and informing medical care.     

Intensive insulin therapy in the critically ill patients.

BACKGROUND: Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known. METHODS: We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter [4.4 and 6.1 mmol per liter]) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter [11.9 mmol per liter] and maintenance of glucose at a level between 180 and 200 mg per deciliter [10.0 and 11.1 mmol per liter]). RESULTS: At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P<0.04, with adjustment for sequential analyses). The benefit of intensive insulin therapy was attributable to its effect on mortality among patients who remained in the intensive care unit for more than five days (20.2 percent with conventional treatment, as compared with 10.6 percent with intensive insulin therapy, P=0.005). The greatest reduction in mortality involved deaths due to multiple-organ failure with a proven septic focus. Intensive insulin therapy also reduced overall in-hospital mortality by 34 percent, bloodstream infections by 46 percent, acute renal failure requiring dialysis or hemofiltration by 41 percent, the median number of red-cell transfusions by 50 percent, and critical-illness polyneuropathy by 44 percent, and patients receiving intensive therapy were less likely to require prolonged mechanical ventilation and intensive care. CONCLUSIONS: Intensive insulin therapy to maintain blood glucose at or below 110 mg per deciliter reduces morbidity and mortality among critically ill patients in the surgical intensive care unit.     

Invasive pulmonary aspergillosis is associated with cytomegalovirus viremia in critically ill patients - A retrospective cohort study

Background/PurposeCytomegalovirus (CMV) viremia is associated with a higher mortality rate and prolonged intensive care unit (ICU) stay for critically ill patients. CMV infection causes transient but substantial immunosuppression for transplant recipients, increasing risk of fungal infection. The association between CMV viremia and invasive pulmonary aspergillosis (IPA) for critically ill patients is still unknown.MethodsWe retrospectively analyzed patients received bronchoalveolar lavage (BAL), galactomannan test, influenza survey and blood CMV viral load test in ICUs of a university hospital between April 2017 and May 2020. Independent risks for IPA were analyzed by multivariable logistic regression.ResultsA total of 136 patients were included. Twenty-one patients had IPA, 48 patients had CMV viremia and 22 patients had influenza. In a multivariable logistic regression model, patients with CMV viremia or influenza had higher IPA risk (adjusted odds ratio, 3.98 and 8.72; 95% CI, 1.26–12.60 and 2.64–28.82; p value = 0.019 and <0.001, respectively.). Patients with detectable CMV in BAL fluid did not have higher IPA risk (crude odds ratio, 0.95; 95% CI, 0.33–2.79; p value = 0.933). After stratifying patients by CMV viral load, the IPA risk is higher for patients with higher viral loads. There is an additive synergistic effect on IPA risk between CMV viremia and influenza infection.ConclusionFor critically ill patients, CMV viremia is an independent risk factor of IPA. Patients with higher blood CMV viral loads have a higher risk of IPA. CMV viremia and influenza have an additive synergistic effect for IPA risk in critically ill patients.     

Invasive pulmonary aspergillosis infection in severely ill COPD patients in pulmonary ward and ICU

PurposeThis study was planned to determine the trends and susceptibility pattern of invasive pulmonary aspergillosis (IPA) in severely ill chronic obstructive pulmonary disease (COPD) patients admitted in pulmonary ward and ICU of our tertiary care centre.MethodsFifty COPD patients suspected of IPA from pulmonary ward and ICU from April 2017 to September 2018 were investigated. Samples were processed by standard methods, culture positive isolates were confirmed by MALDI-TOF MS and antifungal susceptibility testing was performed by microbroth dilution method.ResultsTwenty-two critically ill COPD patients were microbiologically positive for IA infection, of which 13 were classified as putative invasive aspergillosis. The most common comorbid illness associated was diabetes. A. flavus and A. fumigatus were the commonest species isolated. The minimum inhibitory concentration of the antifungals was low. Morbidity due to IPA in COPD patients was very high.ConclusionsPrevalence of IPA in the pulmonary ward and ICU was found to be 9.6%. MALDI-TOF seems to be a promising tool for aiding rapid identification especially for slow growing and non-sporulating fungi. Heightened awareness and suspicion for pulmonary mould infections along with early diagnosis can substantially alter the patient prognosis.     

Management of Critically Ill Patients with Severe Acute Respiratory Syndrome (SARS)

Severe acute respiratory syndrome (SARS) is frequently complicated with acute respiratory failure. In this article, we aim to focus on the management of the subgroup of SARS patients who are critically ill. Most SARS patients would require high flow oxygen supplementation, 20-30% required intensive care unit (ICU) or high dependency care, and 13-26% developed acute respiratory distress syndrome (ARDS). In some of these patients, the clinical course can progress relentlessly to septic shock and/or multiple organ dysfunction syndrome (MODS). The management of critically ill SARS patients requires timely institution of pharmacotherapy where applicable and supportive treatment (oxygen therapy, noninvasive and invasive ventilation). Superimposed bacterial and other opportunistic infections are common, especially in those treated with mechanical ventilation. Subcutaneous emphysema, pneumothoraces and pneumomediastinum may arise spontaneously or as a result of positive ventilatory assistance. Older age is a consistently a poor prognostic factor. Appropriate use of personal protection equipment and adherence to infection control measures is mandatory for effective infection control. Much of the knowledge about the clinical aspects of SARS is based on retrospective observational data and randomized-controlled trials are required for confirmation. Physicians and scientists all over the world should collaborate to study this condition which may potentially threaten human existence.