key: cord-0807406-9umejnef
authors: Montrucchio, G.; Corcione, S.; Sales, G.; Curtoni, A.; De Rosa, F.G.; Brazzi, L.
title: Carbapenem resistant Klebsiella pneumoniae in ICU-admitted COVID-19 Patients: Keep an eye on the ball
date: 2020-11-23
journal: J Glob Antimicrob Resist
DOI: 10.1016/j.jgar.2020.11.004
sha: bfd4e24db9fa687c47703c8f651d4a22d096e1be
doc_id: 807406
cord_uid: 9umejnef

We report the cases of 7 ICU patients with COVID-19 related ARDS, who developed positive rectal swab and invasive infections due to CP-Kp. Notwithstanding the infection prevention measures introduced during COVID-19 pandemic and the changes in the hospitalized population, attention to CP-Kp infections must remain high, especially in critically ill setting.

Bacterial and fungal infections are common complications of viral pneumonia, especially in critically ill patients, as evidenced during 2003 SARS-CoV epidemic, when gram-negative bacteria (GNB) and Candida caused the largest number of secondary infections [1] . It follows, that assessing the risk of difficult-to-treat bacterial superinfections such as GNB is crucial in all suspected cases of 2019-novel coronavirus [2] .

COVID-19 patients are, in fact, particularly at risk of developing super-infections, especially caused by Multi-drug Resistant (MDR) pathogens. This, in spite of the improvement of infection control procedures worldwide adopted during COVID-19 outbreak, the changes in overall hospital admissions for other conditions [3] , the considerably young age and the absence of multiple comorbidities [4] .

Due to the fact that, prior to COVID-19 outbreak, Italy had an endemic situation regarding the spread of MDR infections, mainly due to Carbapenemase producing -Klebsiella pneumoniae (CP-Kp) [5] we evaluated, in the cohort of ICU-patients affected by severe acute respiratory distress syndrome (ARDS) caused by COVID-19 incidence and time course of CP-Kp infections during ICU stay. Detection of carbapenem resistance genes was carried out using the Xpert Carba-R assay (Cepheid, Sunnyvale, CA, USA). Antimicrobial susceptibilities were interpreted according to EUCAST 2019.

Seven patients out of 35 had a positive rectal swab for CP-Kp and bilateral pulmonary infiltrates ( Table 1) . Six developed invasive infections and one was colonized due to CP-Kp during ICU stay (2 were CP-Kp positive at ICU admission). Six out of 7 patients were transferred from other hospitals. Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score (SAPS) and Acute Physiologic Assessment and Chronic Health Evaluation (APACHE II) median score (IQR) at ICU admission were respectively: 12 (11-13), 54 (51-60) and 25 (24-26) while mean MuLBSTA score [6] was 9 (9-10). The median (IQR) duration of COVID-19 symptoms before hospital admission was 7 (4-7) days while median (IQR) duration of ICU stay and mechanical ventilation was 34 (24-40) and 34 (23-40) days, respectively.

(12-19) and 12 (7-15) days, respectively. Six patients developed VAP, and 5 had contextual BSI; in all of them the infection resulted in septic shock with high vasopressors request.

All the patients received hydroxychloroquine, five of them antiviral treatment, four were treated with Tocilizumab. Corticosteroids were given in all, but one cases (dexamethasone 8 mg every 8 hours, with variability according to different hospitals in transferred patients). At ICUadmission, 71,4% of patients had lymphocytopenia. All patients were previously treated with broadspectrum antibiotics (all of them with beta-lactams, 5 with azithromycin, two of them with doxicicline, 3 with vancomycin) in 5 cases with a documented previous bacterial co-infection before Cp-Kp: 3 VAP, 2 BSI, caused by P.aeruginosa (2), K. pneumoniae ESBL (1), Coagulasenegative staphylococci (1) and E. faecium (1) respectively. We observed a death within 28 days and 5 deaths in ICU on 7 patients. Mortality related to CP-Kp septic shock was 28.6%.

Few articles are reporting about secondary infections in COVID-19, but some data confirm that in ICU patients, superinfections were identified in 13.5%-44% of patients, and due to various pathogens, including MDR-GNB [2] .

Known risk factors for the development of Cp-Kp infections do not appear fully applicable in this cohort of patients [4] . In fact, our population was relatively young and free of significant comorbidities, except obesity (57%). The reduction of hospital access for all causes [3] , apart those due to COVID-19, should, at least theoretically, have contributed to a reduction in the dissemination of the MDR pathogens. And infection control procedures are those most implemented in the context of the COVID-19 pandemic to ensure safety for the health care workers, maximizing contact precautions.

Conversely, factors potentially implicated in the risk of MDR infections are the increased patient's transfer induced by the pandemic affecting the whole Northern Italy; the previous broadspectrum antibiotic treatment before hospital admission; the presence of other previous invasive bacterial co-infection; and the severity of our cohort of patient, requiring vv-ECMO support in 71.4% and continuous renal replacement therapy in 28.6%. In particular, in patients undergoing ECMO, colonization by MDR Gram-negative bacteria is frequent and associated with more the tenfold odds for subsequent infections, that are associated with an increased risk of death [7] .

Our results seem to suggest the need to keep major focus on CP-Kp infections even, and especially, among COVID-19 patients, due to their extreme fragility, probably linked to immunological mechanisms still not fully clarified, and their need for prolonged ICU stay. 

The clinical characteristics of secondary infection of lower respiratory in severe acute respiratory syndrome

COVID-19, superinfections and antimicrobial development: What can we expect? Clin Infect Dis

Reduced Rate of Hospital Admissions for ACS during Covid-19 Outbreak in Northern Italy

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Surveillance of antimicrobial resistance in Europe

Clinical features predicting mortality risk in patients with viral pneumoniae: the MuLBSTA score. Front Microbiol

Gastrointestinal colonization with multidrug-resistant

Gram-negative bacteria during extracorporeal membrane oxygenation: effect on the risk of subsequent infections and impact on patient outcome

We thank all the nurses, the collaborators and the residents working in our ICU in the 'Città della Salute e della Scienza' hospital (Turin -Italy) for their precious and continuous collaboration and support.J o u r n a l P r e -p r o o f