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Superbug Meets Opportunistic Infection: A Case Report of Mobilized Colistin Resistance-1–Positive Klebsiella pneumoniae and Candida lusitaniae in a Complex Surgical Patient

Weimer, Jonathan M. MD, MS; Ellis, Dan B. MD

doi: 10.1213/XAA.0000000000000923
Case Reports
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Infection with either mobilized colistin resistance-1 gene–positive gram-negative bacteria or invasive Candida lusitaniae occurs rarely throughout the United States. Here we report the existence of both invasive infections occurring in a single, complex patient who initially presented with necrotizing pancreatitis and gastrointestinal bleeding. We detail the patient’s history and perioperative course for enterocutaneous fistulae takedown and ureteral stenting, describe a template of preventative steps taken in the perioperative environment to prevent nosocomial pathogen transmission, and provide a brief overview of both the mobilized colistin resistance-1 gene and C lusitaniae.

From the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts.

Accepted for publication September 25, 2018.

Funding: None.

The authors declare no conflicts of interest.

Address correspondence to Jonathan M. Weimer, MD, MS, Department of Anesthesia, Critical Care, and Pain Management, Massachusetts General Hospital, 55 Fruit St, GRJ-4–438, Boston, MA 02114. Address e-mail to jweimer@mgh.harvard.edu.

Emergence of antibiotic-resistant organisms has developed into a global health concern extending beyond academic circles. Since its first published report from China,1 the mobilized colistin resistance-1 (mcr-1) gene conferring colistin resistance has been identified in the United States and prompted efforts by the Centers for Disease Control and Prevention to detect, track, and respond to the growing threat.2 Even as historical pathogens continue their evolution and we race to develop new weapons for avoiding a postantibiotic era,3 medical professionals are confronted by microorganisms rarely seen a generation ago. As the immunocompromised patient, prolonged hospitalization, antimicrobial course, or intravascular catheter becomes more prevalent, the door opens for uncommon human pathogens like the fungal species Candida lusitaniae.4

Fortunately, such “superbugs” and opportunistic infections are rare. Fewer than 50 cases of mcr-1 have been identified in the United States,2 while Clusitaniae represents only 1% of yeast isolates in human specimens.5 Here we report the existence of infection with both the mcr-1 gene and invasive Clusitaniae in a single patient. We describe a template of preventative steps taken in the perioperative environment to prevent nosocomial transmission and provide a brief overview of the mcr-1 gene and C lusitaniae. Written consent for publication was obtained from the patient’s legal guardian.

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CASE DESCRIPTION

A 61-year-old man was scheduled for enterocutaneous fistula takedown, cystoscopy, and ureteral stent placement. Medical history was notable for traumatic brain injury with cognitive deficits, insulin-dependent diabetes mellitus, recurrent deep vein thrombosis on anticoagulation, and alcohol abuse with pancreatitis. One year before presentation, the patient experienced necrotizing pancreatitis and gastrointestinal bleeding requiring mesenteric embolization, massive transfusion, and multiple intensive care unit (ICU) admissions for shock. He required several computed tomography–guided percutaneous drainages for peripancreatic and intraabdominal fluid collections, as well as necrosectomy with resulting high-output abdominal enterocutaneous fistulae from the terminal ileum. Wound cultures from intraabdominal collections were positive for mcr-1–positive Klebsiella pneumoniae and Candida glabrata. Before discharge, the patient completed treatment with 14-day courses of vancomycin, imipenem-cilastatin, and micafungin.

Over the next year, the patient was frequently transferred between inpatient rehabilitation and our hospital for numerous complaints including Clostridium difficile pancolitis, Staphylococcus haemolyticus and Kpneumoniae bacteremia, and peripancreatic cyst accumulation. During 1 admission, the patient’s sputum and blood cultures tested positive for Candida, confirmed as C lusitaniae by Quest Diagnostics via matrix-assisted laser desorption/ionization time of flight mass spectrometry. The patient was started on micafungin and underwent echocardiographic and ophthalmologic workup, which was negative. His peripherally inserted central catheter was replaced, and he completed another course of micafungin. In the following months, the patient’s nutritional status and skin condition improved to the point he was scheduled for fistula takedown.

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Preoperative Setup

Given the patient’s history, extensive preoperative planning was held with the Massachusetts General Hospital Infection Control Unit, General Surgery, Anesthesia, and Perioperative Nursing departments to prevent nosocomial transmission of the mcr-1 gene. The morning of surgery, the patient was transported by ambulance from inpatient rehabilitation to a private room. Standard and contact precautions maintained throughout the hospitalization included mandatory hand hygiene, gowning, and gloving before patient interaction. Soiled linen receptacles remained in the patient’s room, and any items removed from the room required immediate disinfection, either by bleach wiping of surfaces or, in the case of reusable medical equipment, by routine sterilization protocols.

The operating room (OR) was modified to maintain a “clean versus dirty” distinction for supplies and personnel. Supplies and personnel became “dirty” on contacting the patient or his belongings. Nonessential equipment was removed and disposable equipment preferentially obtained. Cabinets were labeled with placards stating that hand hygiene with CalStat Plus antiseptic scrub (Steris Life Sciences, Mentor, OH; a 65% ethyl alcohol–based waterless scrub effective against drug-resistant organisms including Staphylococcus and Enterococcus species) must be performed before opening. Trash receptacles with red biohazard bags were available for all discarded waste.

The anesthesia environment was divided into clean and dirty regions. The dirty environment included the anesthesia machine, monitors, pumps, warming devices, and a tray with medications, airway, and intravenous supplies. A clean environment existed behind the workstation containing the Omnicell with medications, replacement supplies, and specialized vascular access equipment.

Additional OR staff with specialized roles helped maintain precautions. The nursing team included 4 individuals:

  1. Scrub nurse
  2. Circulator assuming a “dirty” role and assisting with positioning
  3. Circulator assuming a “clean” role and responsible for documenting and retrieving supplies within the OR, and monitoring contact precautions
  4. External circulator managing traffic into the OR and retrieving outside supplies

Two anesthesia providers were present throughout the case. A “dirty” provider was responsible for direct patient contact, monitoring, and airway/medication/line management. A “clean” provider mixed medications, passed supplies to the “dirty” provider, and monitored adherence to contact precautions.

Three providers traveled to the preoperative holding area to transport the patient to the OR. Two providers in contact with the patient and bed wore gown and gloves. The third provider did not wear personal protective equipment and ensured that contact precautions were followed, opened doors, cleared obstacles from hallways, and operated the elevator. On OR arrival, the patient was transferred to the OR table, and the stretcher was removed for immediate bleaching. The main door was locked to prevent unnecessary traffic, and access to the OR was maintained through a side door monitored by the external circulator nurse. Bleach-soaked towels were placed on the floors outside the OR entrance for providers to clean their shoes when exiting.

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Operative Course

Standard American Society of Anesthesiology monitors were applied, preoxygenation performed, and anesthesia induced. Intubation was performed using a disposable laryngoscope. General anesthesia was maintained with sevoflurane, oxygen, and air delivered by a Dräger Apollo machine (Draeger, Telford, PA) equipped with a standard disposable circuit and air filter connected to the endotracheal tube. Hydromorphone and cisatracurium were dosed as needed.

After induction and lithotomy positioning, the urologists performed a cystoscopy and ureteral stent placement. The urologists then broke scrub, performed hand hygiene, and proceeded to the locker room to change. The patient was repositioned supine, prepared, and draped. The abdominal wall was resected at the site of the fistula along with underlying bowel. The patient tolerated the procedure, was successfully extubated, and transferred to a private ICU room.

Per the prearranged transport plan, 3 providers again transported the patient. Once care was transitioned to the ICU team, OR providers removed their soiled gowns and gloves, performed hand hygiene, and proceeded to change scrubs. In the OR, surgical equipment was removed for sterilization according to equipment protocol, while objects and surfaces within the OR were wiped with bleach solution. After 12 days, the patient was discharged to his rehabilitation hospital where he is recuperating. Standard and contact precautions remain in place. No known transmission of the mcr-1 infection has occurred, per hospital observation for colistin-resistant gram-negative organisms.

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DISCUSSION

Infection with mcr-1–positive gram-negative bacteria and invasive C lusitaniae occurs rarely in the United States. For the first time, we describe a report of both infections occurring in a single patient.

Mcr-1 was identified in Kpneumoniae from our patient’s intraabdominal cultures after multiple procedures to drain peripancreatic and intraabdominal fluid. The initial discovery and characterization of the mcr-1 plasmid were alarming for the possibility of widespread transmission of colistin resistance within the Enterobacteriaceae family, even in the absence of selection pressure.1 In isolates already harboring carbapenemase genes, mcr-1 can potentially give rise to bacterial strains resistant to nearly all existing antibiotics.6 Subsequent analyses demonstrated the disturbingly high prevalence of mcr-1 in livestock and food isolates, with global trade representing a means of widespread dissemination.7 Surveillance programs have confirmed global spread of mcr-1 in human isolates.8 Meanwhile, recent investigations continue to report on the existence of newly identified colistin resistance genes.9

Septic shock secondary to C lusitaniae fungemia also occurred in our patient despite no known malignancy or immunodeficiency syndrome. However, his risk factors for invasive candidiasis included severe pancreatitis, multiple surgical procedures, prolonged hospitalizations with courses of broad-spectrum antibiotics, an indwelling central catheter, and dependence on total parenteral nutrition. C lusitaniae was first identified as a human pathogen in a 1979 case of acute myelogenous leukemia and was notable for rapid development of resistance to amphotericin B.10 Biofilm formation for C lusitaniae is significantly higher compared to other Candida species,11 while mutation or altered expression of ergosterol biosynthetic genes may confer it resistance to amphotericin B.12

Table.

Table.

The increasing prevalence of multidrug-resistant organisms may ultimately require institutions to adapt perioperative practices, with logistics of care depending on factors such as pathogen, location, procedure, and hospital policy. The Centers for Disease Control and Prevention offers extensive guidance for preventing transmission of infectious agents,13 while the recent Ebola epidemic has prompted the American College of Surgeons to offer its own perioperative guidance.14 Similarly, our case highlights several core areas that should be addressed to help prevent the nosocomial spread of resistant pathogens during the perioperative period (Table).

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DISCLOSURES

Name: Jonathan M. Weimer, MD, MS.

Contribution: This author helped care for the patient, and research, draft and edit the manuscript.

Name: Dan B. Ellis, MD.

Contribution: This author helped care for the patient, and research, draft and edit the manuscript.

This manuscript was handled by: BobbieJean Sweitzer, MD, FACP.

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REFERENCES

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