Epidemic timeline and patient characteristics

On July 26, the Microbiology laboratory notified the hospital infection control unit of a potential outbreak of S. marcescens resistant to all tested antibiotics, which was isolated in 3 blood cultures of different patients, within a period of 2 weeks. The 3 patients were in the Trauma ICU within 5–7 meters from each other. Despite infection control efforts for almost 3 weeks, the XDR S. marcescens was isolated from endotracheal tube sample of another patient. This patient was also in the Trauma ICU in close range to the initial three cases, prior to the implementation of cohort measures.

All 3 initial patients, who presented with bacteremia, had central venous lines and were under mechanical ventilation (Table 1). The index case, who had been hospitalized for approximately 2 months, was receiving hemodialysis.

Table 1. Patients’ characteristics, S. marcescens infection information, and clinical outcomes

Note.

* Outcome 30 d post S. marcescens diagnosis. ICU, intensive care unit; CVC, central venous catheter; MV, mechanical ventilation; HD, hemodialysis; EVD, external ventricular drain; IAA, intra-abdominal abscess; CRAB, carbapenem-resistant Acinetobacter baumannii.

As presented in Table 1, 1 patient presented with ventriculitis caused by the XDR S. marcescens. The combination of Ceftazidime-Avibactam and Aztreonam was considered by the infection control team. However, the 2 antibiotics were not available to treat the patients. Meropenem and Amikacin was the regimen chosen to treat most patients due to potential synergy and availability. ^{Reference Kulengowski, Rutter, Campion, Lee, Feola and Burgess8} One of the 4 patients, who was also infected with an Acinetobacter baumannii, was treated with Meropenem and Tigecycline.

Microbiological and genomic results

Initial automated susceptibility testing on the S. marcescens isolates from the 4 patients were resistant to all tested antibiotics. Additional susceptibility testing using a modified Stokes disc diffusion method showed that, except for Fosfomycin (intravenous formulation not available in Brazil), the isolates were resistant to all 29 antibiotics. Genomic testing of the main resistance genes in the 4 Serratia isolates detected the bla _NDM gene in all isolates, and the bla _KPC only in 2 of the 4 isolates. Strains carrying the respective genes were used as controls for PCR reactions. Nucleotide sequence accession numbers of control strains: MH818574 and MH818573. Other genes that were investigated (i.e. bla _VEB, bla _IMP, bla _VIM, bla _CTX-M-Gp8, bla _CTX-M-Gp9,) were not detected. Phenotypic metallo-b-lactamases production test was positive in all 4 isolates. As shown in Figure 1, the ERIC-PCR demonstrated 100% genetic similarity among the 4 bacterial isolates and suggested horizontal transmission.

Figure 1. Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction of Serratia marcescens isolates from samples of 4 patients. SM1: S. marcescens isolate from patient 1, SM2: S. marcescens isolate from patient 2, SM3: S. marcescens isolate from patient 3, SM4: S. marcescens isolate from patient 4.

Containment and investigation

As soon as the first patients were identified, all parties involved in the assistance, surveillance, and infection control, as well as local health authorities, were notified and control measures put in place, including a) cohorting of patients and health care professionals assisting those infected/colonized, b) creation of a closed physical border for the cohort area, c) installation of personal protective equipment stations at the entrance of the cohort area, d) reinforcement of hand hygiene and contact precaution training of health care personnel working in the trauma ICU covering all shifts, f) limitation of new admissions and patient transfer, g) weekly testing of contacts, h) strengthening of environmental and equipment decontamination protocols, i) revision of water and dialysis fluids periodic analyses, j) daily monitoring of clinical status and laboratory data of infected/colonized; and k) daily monitoring of microbiology results of the all hospitalized patients.

Investigation efforts were also put in place to identify common risk factors among the infected/colonized, as well as to review the health assistance processes, including storage, preparation, and administration of solutions and medications. The fact that the 4 patients infected with the XDR S. marcescens were 5–7 meters from each other, as well as were under mechanical ventilation and had central venous lines raised the possibility of patient cross-transmission.

Inspection visits to the medication and solution storage room and preparation station were performed, however, protocol deviations were not identified. During the retraining of health care personnel, we could not identify any misconception regarding preparation and administration of solutions and medications. Microbiological sampling of the environment was performed, particularly of faucets and hemodialysis water supply. However, the XDR S. marcescens was not identified. Periodic analyses of water and dialysis fluids were revised and results were according to standards.

Weekly testing of contacts using rectal swabs was carried out until 2 consecutive weeks without any infection or colonization were registered. All hospital microbiological test results were daily monitored for up to a month after the last XDR S. marcescens was detected in the hospital.