International study of the prevalence and outcomes of infection in intensive care units

The clinical presentation of Aspergillus lung disease is determined by the interaction between fungus and host. Invasive aspergillosis develops in severely immunocompromised patients, including those with neutropenia, and increasingly in the non-neutropenic host, including lung transplant recipients, the critically ill patients and patients on steroids. A high index of suspicion is required in patients without the classical risk factors as early presentation is usually silent and non-specific, pyrexia uncommon and timely treatment is crucial for survival. Invasive aspergillosis has also been diagnosed in normal hosts after massive exposure to fungal spores. Chronic pulmonary aspergillosis affects patients without obvious immune compromise, but with an underlying lung condition such as COPD or sarcoidosis, prior or concurrent TB or non-tuberculous mycobacterial disease. Aspergillus bronchitis may be responsible for persistent respiratory symptoms in patients with Aspergillus detected repeatedly in sputum without evidence of parenchymal Aspergillus disease, especially in patients with bronchiectasis and cystic fibrosis. Allergic bronchopulmonary aspergillosis affects patients with asthma and cystic fibrosis, and is important to recognise as permanent lung or airways damage may accrue if untreated. Changes in the classification of Aspergillus allergic lung disease have been proposed recently. Cases of extrinsic allergic alveolitis and chronic pulmonary aspergillosis have been observed after Aspergillus exposure. Asymptomatic colonisation of the respiratory tract needs close monitoring as it can lead to clinical disease especially with ongoing immunosuppression. The various syndromes should be viewed as a semicontinuous spectrum of disease and one form may evolve into another depending on the degree of ongoing immunosuppression.

https://thorax.bmj.com/content/thoraxjnl/70/3/270.full.pdf

The clinical spectrum of pulmonary aspergillosis

Shahid Husain, MD, MS, Amparo Sole, MD, PhD, Barbara D. Alexander, MD, MHS, Saima Aslam, MD, MS, Robin Avery, MD, Christian Benden, MD, Eliane M. Billaud, PharmD, PhD, Daniel Chambers, MBBS, MD, Lara Danziger-Isakov, MD, Savitri Fedson, MD, Kate Gould, MD, Aric Gregson, MD, Paolo Grossi, MD, PhD, Denis Hadjiliadis, MD, Peter Hopkins, MD, Me-Linh Luong, MD, Debbie J.E. Marriott, MD, Victor Monforte, MD, Patricia Munoz, MD, PhD, Alessandro C. Pasqualotto, MD, PhD, Antonio Roman, MD, Fernanda P. Silveira, MD, Jeffrey Teuteberg, MD, MS, Stephen Weigt, MD, Aimee K. Zaas, MD, MHS, Andreas Zuckerman, MD, and Orla Morrissey, MD, PhD

The 2015 International Society for Heart and Lung Transplantation Guidelines for the management of fungal infections in mechanical circulatory support and cardiothoracic organ transplant recipients: Executive summary

Antimicrobials are among the most important and commonly prescribed drugs in the management of critically ill patients and beta-lactams are the most common antibiotic class used Critically ill patient’s pathophysiological factors lead to altered pharmacokinetics and pharmacodynamics of beta-lactams A comprehensive bibliographic search in PubMed database of all English language articles published from January 2000 to December 2017 was performed, allowing the selection of articles addressing the pharmacokinetics or pharmacodynamics of beta-lactam antibiotics in critically ill patients In critically ill patients, several factors may increase volume of distribution and enhance renal clearance, inducing high intra- and inter-patient variability in beta-lactam concentration and promoting the risk of antibiotic underdosing The duration of infusion of beta-lactams has been shown to influence the fT > minimal inhibitory concentration and an improved beta-lactam pharmacodynamics profile may be obtained by longer exposure with more frequent dosing, extended infusions, or continuous infusions The use of extracorporeal support techniques in the critically ill may further contribute to this problem and we recommend not reducing standard antibiotic dosage since no drug accumulation was found in the available literature and to maintain continuous or prolonged infusion, especially for the treatment of infections caused by multidrug-resistant bacteria Prediction of outcome based on concentrations in plasma results in overestimation of antimicrobial activity at the site of infection, namely in cerebrospinal fluid and the lung Therefore, although no studies have assessed clinical outcome, we recommend using higher than standard dosing, preferably with continuous or prolonged infusions, especially when treating less susceptible bacterial strains at these sites, as the pharmacodynamics profile may improve with no apparent increase in toxicity A therapeutic drug monitoring-guided approach could be particularly useful in critically ill patients in whom achieving target concentrations is more difficult, such as obese patients, immunocompromised patients, those infected by highly resistant bacterial strains, patients with augmented renal clearance, and those undergoing extracorporeal support techniques

/pdf/pharmacokinetics-pharmacodynamics-issues-relevant-for-the-3swurlfons.pdf

Pharmacokinetics–pharmacodynamics issues relevant for the clinical use of beta-lactam antibiotics in critically ill patients

Pharmacokinetic and Pharmacodynamic Principles of Anti-infective Dosing

Isolation of Aspergillus species from the airway of lung transplant recipients is associated with excess mortality

Pulmonary infections in critically ill patients are common and are associated with high morbidity and mortality. Piperacillin-tazobactam is a frequently used therapy in critically ill patients with pulmonary infection. Antibiotic concentrations in the lung reflect target-site antibiotic concentrations in patients with pneumonia. The aim of this study was to assess the plasma and intrapulmonary pharmacokinetics (PK) of piperacillin-tazobactam in critically ill patients administered standard piperacillin-tazobactam regimens. A population PK model was developed to describe plasma and intrapulmonary piperacillin and tazobactam concentrations. The probability of piperacillin exposures reaching pharmacodynamic end points and the impact of pulmonary permeability on piperacillin and tazobactam pulmonary penetration was explored. The median piperacillin and tazobactam pulmonary penetration ratios were 49.3 and 121.2%, respectively. Pulmonary piperacillin and tazobactam concentrations were unpredictable and negatively correlated with pulmonary permeability. Current piperacillin-tazobactam regimens may be insufficient to treat pneumonia caused by piperacillin-tazobactam-susceptible organisms in some critically ill patients.

https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2014.131

Pulmonary penetration of piperacillin and tazobactam in critically ill patients.

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Isolation of Aspergillus species from the airway of lung transplant recipients is associated with excess mortality

Pulmonary penetration of piperacillin and tazobactam in critically ill patients.