Description of outbreak

Three cases of CPE identified from sputum samples of patients managed for severe COVID-19 infection in an intensive-care department over a 3-month period raised suspicion for transmission of carbapenem resistance genes and triggered outbreak surveillance (Figure 1: Epidemic curve). A subsequent fourth case of CPE beyond surveillance was not deemed significant.

Figure 1.

Epidemic curve identifying cases of carbapenemase-producing Enterobacterales (CPE) in the intensive care unit (ICU) between November 2021 and April 2022 and results of weekly CPE screening in patients within the ICU conducted between February to March 2022.

This intensive-care department within the hospital is a 24-bed ward with a single-room model of care with 1 nurse allocated per patient (Figure 2: Floor plan).

Figure 2.

Floor plan of intensive-care department at Barwon Health, University Hospital Geelong, depicting the shared room spaces by identified cases of carbapenemase-producing Enterobacterales.

Case 1 is a 64-year-old man with a history of dilated cardiomyopathy, atrial fibrillation, type-2 diabetes mellitus (T2DM), hypertension, and active smoking and no history of COVID-19 vaccination. He presented in October 2021 with severe COVID-19 infection requiring intensive-care admission and intubation on day 2. Management included corticosteroids and baricitinib for COVID-19 infection and empirical piperacillin/tazobactam for presumed concurrent severe CAP. On day 20, wean to tracheostomy care was made. The intensive-care stay was complicated by end-stage kidney injury requiring renal replacement therapy, arrhythmia, critical illness myopathy, and multiple infectious complications including Staphylococcus epidermidis line-related infection requiring vancomycin therapy for 1 week, severe Clostridioides difficile infection requiring intravenous metronidazole and oral vancomycin for 10 days and a repeated course of vancomycin for C. difficile recurrence within 2 weeks. The patient was managed for ventilator-associated pneumonia within 30 days of admission with a sensitive Pseudomonas aeruginosa isolated on a sputum sample with piperacillin/tazobactam for 7 days.

On day 39, subsequent sputum sampling revealed persistent Pseudomonas growth alongside isolation of a carbapenemase-producing Escherichia coli with the detection of an OXA-48-like resistance gene (OXA-244 allele, multi-locus sequence typing [MLST] type 10) on further testing. Initially, ciprofloxacin was commenced based on the sensitivity profile; however, further respiratory deterioration prompted repeated sputum samples revealing the CPE E. coli had acquired fluoroquinolone resistance (Table 1: Susceptibility). A combination of ceftazidime/avibactam and amikacin was commenced for 14 days with respiratory recovery and decannulation on day 73 with subsequent discharge from intensive care on day 75. The patient died on day 77 from a presumed aspiration event and subsequent respiratory arrest.

Table 1.

Antimicrobial susceptibility testing of carbapenemase-producing Enterobacterales organisms identified in outbreak cases in intensive care at Barwon Health, University Hospital Geelong

Note. MIC, minimal inhibitory concentration; S, susceptible; R, resistant.

Case 2 is a 78-year-old man with a history of hypertension, nonsmoker, and 2 previous AstraZeneca™ vaccines for COVID-19. He presented in late November 2021 with dyspnea with transition to intensive care for intubation for progressive respiratory distress on day 3. He was managed with dexamethasone, remdesivir, and baricitinib for severe COVID-19 infection and randomized to moxifloxacin as part of a clinical trial for CAP.

On day 12, a carbapenemase-producing Enterobacter cloacae was identified from purulent sputum; however; in the absence of a clinical syndrome consistent with pneumonia, this pathogen was initially not treated. This isolate harbored resistance genes IMP-4, MCR-9, ACT-37, and SHV-12 (MLST type 269) with susceptibility profile summarized in Table 1.

On day 18, a transition to tracheostomy was made. Given the repeated isolation of CPE on sputum samples over 4 days and the high risks for respiratory deterioration, a decision was made to commence targeted CPE treatment with a combination of amikacin and ceftazidime/avibactam for a total of 10 days. The patient was decannulated on day 26 and discharged from hospital care on day 42.

Case 3 is a 67-year-old man with a history of T2DM, hypertension, obesity, and active smoking and no history of COVID-19 vaccination. He presented in early January 2022 with dyspnea secondary to COVID-19 requiring intubation. He was commenced on ceftriaxone, azithromycin, and flucloxacillin for isolation of E. coli (amoxicillin resistant) and methicillin-sensitive Staphylococcus aureus on sputum sample on day 1. On day 1, the sputum sample isolated E. coli with an increasingly resistant pattern (resistant ampicillin, third-generation cephalosporins, and sensitive gentamicin and ciprofloxacin). The transition was made to intravenous ciprofloxacin for E. coli and cefazolin for S. aureus to reduce the risk of renal toxicity given severe acute kidney injury requiring continuous renal replacement therapy. Antimicrobials were ceased on 13 with the transition to tracheostomy on day 14.

On day 19, the patient developed respiratory and hemodynamic compromise requiring inotropic support. Sputum sample isolated E. coli, which prompted the broadening of antimicrobial coverage to meropenem. Within 24 hours the laboratory confirmed a positive CIM test, consistent with carbapenemase production. The reference laboratory confirmed CPE was found to harbor the IMP resistance gene and alleles IMP-4 and MCR-9 (MLST type 69). Given ongoing deterioration, a transition to ceftazidime/avibactam and aztreonam was made prior to susceptibility confirmation, which subsequently revealed resistance (Table 1: Susceptibility). Despite use for 7 days, clinical recovery was achieved with the patient decannulated on day 38.

On day 49, Enterococcus faecalis was identified in blood cultures with a urinary focus managed with intravenous ampicillin, concurrent respiratory sample again isolated the CPE E. coli; however, given respiratory stability, therapy was not commenced. A discharge to rehab care was made on day 56 with discharge home on day 68.

Case 4 is a 65-year-old male with a history of ischemic heart disease, chronic obstructive pulmonary disease, active smoking, and penicillin allergy and no history of COVID-19 vaccination who presented with out-of-hospital cardiac arrest requiring percutaneous coronary intervention in March 2022. He presented within 2 weeks with cough and dyspnea and was found to have type-2 respiratory failure due to left lower lobe pneumonia requiring inotropic supports, intubation, and admission to the intensive care unit on day 1. He was commenced on vancomycin, cefepime, and azithromycin for severe CAP with early transition to intravenous ceftriaxone and azithromycin for 10 days.

He failed extubation on day 5 due to progressive respiratory failure and required tracheostomy on day 14, complicated by tracheal bleeding requiring extraction of obstructive clots in theater. On day 19, increasing sputum production led to the isolation of Enterobacter cloacae found to harbor resistance genes IMP-4 and MCR-9 (MLST type 269) with susceptibilities summarized in Table 1. This was managed with amikacin and aztreonam and transitioned to amikacin based on sensitivity profile for 10 days until day 29. The patient underwent decannulation on 30; however, was transitioned to end-of-life care due to recurrent aspiration and respiratory decline. He died on day 52.