Lung abscess following ventilator-associated pneumonia during COVID-19: a retrospective multicenter cohort study.

BACKGROUND: Patients undergoing mechanical ventilation (MV) for COVID-19 exhibit an increased risk of ventilator-associated pneumonia (VAP). The occurrence of lung abscesses following VAP in these patients has been poorly studied. We aimed to describe the incidence, characteristics, risk factors and prognosis of lung abscesses complicating VAP after COVID-19. METHODS: We conducted an observational, retrospective study in three French intensive care units. Patients admitted for acute respiratory failure with a confirmed SARS-CoV-2 PCR and requiring MV for more than 48 h were included. RESULTS: Among the 507 patients included, 326 (64%) had a documented VAP. Of these, 23 (7%) developed a lung abscess. Enterobacterales (15/23, 65%) were the main documentation, followed by non-fermenting Gram-negative bacilli (10/23, 43%) and Gram-positive cocci (8/23, 35%). Lung abscesses were mainly plurimicrobial (15/23, 65%). In multivariate analysis, a plurimicrobial 1st VAP episode (OR (95% CI) 2.93 (1.16-7.51); p = 0.02) and the use of hydrocortisone (OR (95% CI) 4.86 (1.95-12.1); p = 0.001) were associated with lung abscess development. Intensive care unit (ICU) mortality of patients with lung abscesses reached 52%, but was not significantly higher than for patients with VAP but no lung abscess. Patients with lung abscesses had reduced ventilator-free days at day 60, a longer duration of MV and ICU stay than patients with VAP but no lung abscess (respectively, 0 (0-3) vs. 16 (0-42) days; p < 0.001, 49 (32-73) vs. 25 (11-41) days; p < 0.001, 52 (36-77) vs. 28 (16-47) days; p < 0.001). CONCLUSIONS: Lung abscessing pneumonia is not uncommon among COVID-19 patients developing VAP. A plurimicrobial first VAP episode and the use of hydrocortisone are independently associated with this complication. In COVID-19 patients with persistent VAP, a chest CT scan investigating the evolution toward lung abscess should be considered.

Aminoglycosides in critically ill patients: which dosing regimens for which pathogens?

Modifications of antibiotic pharmacokinetic parameters have been reported in critically ill patients, resulting in a risk of treatment failure. We aimed to determine optimised amikacin (AMK), gentamicin (GEN) and tobramycin (TOB) intravenous dosing regimens in this patient population. Patients admitted to the medical ICU and treated with AMK, GEN or TOB were included. Analyses were performed using a parametric population approach. Monte Carlo simulations were performed and the probability of target attainment (PTA) was calculated using Cmax/MIC ≥ 8 and trough concentrations as targets. A total of 117 critically ill hospitalised patients were studied. Median values (interindividual variability, É·2) of clearance were 3.51 (0.539), 3.53 (0.297), 2.70 (0.339) and 5.07 (0.339) L/h for AMK, GEN, TOB, and TOB in cystic fibrosis (CF), respectively. Median values (É·2) of central volume of distribution were 30.2 (0.215), 20.0 (0.109) and 25.6 (0.177) L for AMK, GEN and TOB, respectively. Simulations showed that doses should be adjusted to actual body weight and creatinine clearance (CLCR) for AMK and GEN, and according to CLCR and presence of CF for TOB. In conclusion, our recommendations for treating Pseudomonas aeruginosa infections in this population include using initial doses of 35 mg/kg for AMK or 10 mg/kg for TOB (CF and non-CF patients). GEN demonstrated the best rates of target attainment against Staphylococcus aureus infections with a dose of 5 mg/kg. As high aminoglycoside doses are required in this population, efficacy and safety targets are conflicting and therapeutic drug monitoring remains an important tool to manage this issue.

Influenza-induced acute respiratory distress syndrome during the 2010-2016 seasons: bacterial co-infections and outcomes by virus type and subtype.

OBJECTIVES: We aimed to describe bacterial co-infections and acute respiratory distress (ARDS) outcomes according to influenza type and subtype. METHODS: A retrospective observational study was conducted from 2012 to 2016 in patients admitted to the respiratory intensive care unit (ICU) of Marseille university hospital for influenza-induced ARDS. Microbiological investigations, including multiplex molecular respiratory panel testing and conventional bacteriological cultures, were performed as part of the routine ICU care on the bronchoalveloar lavage collected at admission. Bacterial co-infections, ICU mortality and respiratory function were investigated according to virus type and subtype. RESULTS: Among the 45 ARDS patients included, A(H1N1)pdm09 was the most frequent influenza virus identified (28/45 A(H1N1)pdm09, eight out of 45 A(H3N2) and nine out of 45 influenza B). Bacterial co-infections involving a total of 23 bacteria were diagnosed in 16/45 patients (36%). A(H1N1)pdm09 patients presented fewer bacterial co-infections (17.9% vs. 50.0% for A(H3N2) patients and 77.8% for B patients; p < 0.01). Overall, mortality at 90 days post admission was 33.3% (15/45), and there was no significant difference between influenza type and subtype. The need for extracorporeal membrane oxygenation was more frequent for A(H1N1)pdm2009 (20/28, 71.4%) and B patients (7/9, 77.8%) than the A(H3N2) subtype (1/8, 12.5%; p < 0.01). A(H1N1)pdm09-ARDS patients were associated with fewer ventilation-free days at day 28 (median (IQR): 0 (0-8) days) compared with other influenza-ARDS patients (15 (0-25) days, p < 0.05). DISCUSSION: In a population of influenza-induced ARDS, A(H1N1)pdm09 was associated with fewer bacterial co-infections but poorer respiratory outcomes. These data underline the major role of A(H1N1)pdm09 subtype on influenza disease severity.

Cytomegalovirus reactivation enhances the virulence of Staphylococcus aureus pneumonia in a mouse model.

OBJECTIVES: Cytomegalovirus (CMV) reactivation in intensive care unit patients may increase mortality and favour bacterial pneumonia. We developed a murine model to compare the severity of staphylococcal pneumonia after CMV reactivation and in CMV-negative mice. METHODS: Balb/c mice were primo-infected with murine cytomegalovirus (MCMV n=90) or received saline (control n=90). After latency, all mice underwent caecal ligation and puncture to trigger MCMV reactivation in MCMV primary-infected mice. Surviving animals received an intra-nasal inoculation with methicillin-susceptible Staphylococcus aureus (MSSA) to induce pneumonia. Mortality, lung bacterial count, histology and interferon-alpha and gamma serum levels were compared in MCMV reactivated and control mice 2, 5 and 15 days after pneumonia. RESULTS: After MSSA pneumonia, MCMV mice showed a trend towards a higher mortality (9.4% versus 0%; p 0.09) and a higher weight loss (2.2 (0.6-4.1 g) versus 0.7 (-0.3 to 1.3 g); p 0.005). The lung bacterial count was higher in MCMV mice 2 days (5×103 (103 to 3×105) versus 102 (0 to 4×102) CFU/lung; p 0.007) and 5 days (2.5×104 (1.6×104 to 6.5×105) versus 15 (10-40) CFU/lung; p 0.005) after MSSA pneumonia. 8/40 (20%) MCMV mice developed lung abscesses compared to 0% in control (p 0.011). Interferon-alpha serum levels 2 days after staphylococcal pneumonia were higher in MCMV mice. CONCLUSIONS: MCMV reactivation decreased lung bacterial clearance and favoured the development of staphylococcal abscessing pneumonia. CMV reactivation may be responsible for a higher susceptibility to bacterial sepsis.

Statin therapy in critically-ill patients with severe sepsis: a review and meta-analysis of randomized clinical trials.

UNLABELLED: While statins are indicated to reduce blood cholesterol levels, they also have anti-inflammatory and immunomodulatory effects. Several observational cohort studies suggested that statins may improve survival and reduce complications in patients with sepsis. Recent randomized controlled studies in critically ill patients have been conducted and published. In this paper we present a meta-analysis of these randomized trials. METHODS: An electronic article search through PubMed was performed. Only randomized controlled trials including critically ill adult patients with severe sepsis were retained. A meta-analysis was performed as detailed in text below. Overall analysis including 1818 patients total from 4 studies showed that there was no difference in 60-day mortality between statins (223/903) and placebo (233/899) [risk ratio, 0.930; 95% CI, 0.722 to 1.198]. Similarly, no difference in 28-day mortality was observed between groups (statins 191/907, placebo 199/911; risk ratio 0.953; 95% CI, 0.715 to 1.271). The results of this meta-analysis confirm that the use of statin therapy should not be recommended in the management of severe sepsis in critically ill patients. Statins should be continued with caution and only if necessary, as one study reported that the statin group had a higher rate of hepatic and renal failure.

Outbreak of adenovirus type 1 severe pneumonia in a French intensive care unit, September-October 2012.

We herein describe and analyse the first outbreak of severe pneumonia caused by human adenovirus type1 (HAdV C type 1), which included immunocompetent patients in an intensive care unit (ICU) of Marseille, France, and occurred between September and October 2012. Seven successive patients were diagnosed by HAdV specific real-time polymerase chain reaction with a positive bronchoalveolar lavage. After the collection of nasopharyngeal swabs from healthcare workers, three nurses working night shifts tested positive for HAdV C including one that had exhibited respiratory signs while working one week before the outbreak. She was the most likely source of the outbreak. Our findings suggest that HAdV-1 could be considered as a possible cause of severe pneumonia even in immunocompetent patients with a potential to cause outbreaks in ICUs. HAdV rapid identification and typing is needed to curtail the spread of this pathogen. Reinforcing hand hygiene with antiseptics with demonstrated activity against non-enveloped viruses and ensuring that HCWs with febrile respiratory symptoms avoid direct patient contact are critical measures to prevent transmission of HAdV in healthcare settings.

Disseminated Mycobacterium lentiflavum responsible for hemophagocytic lymphohistocytosis in a man with a history of heart transplantation.

Mycobacterium lentiflavum is a nontuberculous, slowly growing mycobacterium usually recognized as a contaminant. Here, we report a case of disseminated M. lentiflavum infection responsible for hemophagocytic lymphohistocytosis in a heart-transplanted man.

Prone positioning during veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in adults.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is an effective rescue therapy for improving oxygenation in selected severe acute respiratory distress syndrome (ARDS). Prone position (PP) is usually considered before vvECMO and few data are available on the association of PP during VV-ECMO. Thus, we investigated the effect on oxygenation and the safety of PP during vvECMO. METHODS: During a two-year period, 15 patients with severe ARDS were turned into PP during VV-ECMO therapy for at least one of the three following conditions: severe hypoxemia (PaO2/FiO2 ratio below 70) despite maximal oxygenation, injurious ventilation parameters with plateau pressure exceeding 32 cmH2O or failure of attempt to wean ECMO after at least 10 days on ECMO support. RESULTS: PP was considered after a median of 9 days of ECMO and applied for a median of 12 hours and an average of 1.4 sessions per patient resulting in a total of 21 procedures. We found significant improvement in PaO2/FiO2 ratio at 6 hours (P=0.03) and 12 hours (P=0.007) after reversal. The improvement in oxygenation has still persisted 1hour (P=0.017) and 6 hours (P=0.013) after back to the supine position. No change in PaCO2, respiratory system (RS) compliance was observed. ECMO flow was maintained constant during the procedure. No complication related to PP was detected. CONCLUSION: PP may be considered in selected patients difficult to wean or remaining very hypoxemic despite VV-ECMO support.