An 18-year-old adult, Hispanic male was presented to the Emergency Department (ED) by his family via personal automobile. According to the family, the patient was unconscious for approximately 10 minutes during which time he did not receive cardiopulmonary resuscitation (CPR). Upon arrival, he was found to be in cardiac arrest; the patient was not alert or oriented to person, place, or time, cool to the touch, had no agonal respirations, no radial pulse on palpation, no activity on cardiac monitor, no heartbeat on auscultation, pupils that were equal, and 4 mm dilated but non-reactive. The patient's Glasgow Coma Scale score was 3. A CPR protocol was initiated immediately. Spontaneous circulation was achieved after three rounds of epinephrine administration. The patient was admitted to an isolated room in the Intensive Care Unit (ICU), intubated, and placed on a ventilator with a sedation regimen. A 12-lead EKG was obtained following stabilization of the patient demonstrating ST changes consistent with lateral wall ischemia (Figure 1).
Vital signs, laboratory values, including a toxicology screen, and urinalysis (Table 1) were all unremarkable; urine culture had no growth (Table 2). COVID-19 and Rapid Viral Panel testing, including for influenza were returned as negative. Preliminary treatment for sepsis and leukocytosis included intravenous 3.375 g combination piperacillin-tazobactam q.8.h. and 1,000 mg vancomycin q.d.
Blood samples from two access sites for culture and gram stain were collected. Draws from both sites grew C. diphtheriae (anaerobic bottles) and Klebsiella pneumoniae (both aerobic and anaerobic bottles) as identified with polymerase chain reaction (PCR) analysis (Table 2). The New York State Department of Health (NYDOH) and the U.S.'s Center for Disease Control's (CDC) Emergency Operations Center were contacted promptly. Patient samples were shipped overnight for confirmatory testing. Per that NYDOH laboratory, again real time PCR amplified C. diphtheriae DNA, but not toxin A or toxin B DNA fragments.
The patient's social and vaccination history was accertained. The patient was reported to have immigrated to the U.S. from Honduras 3 years prior at the age of 15. At the time of admission, he did not have citizenship, but had attended public high school, which requires by New York State Public Health law, documentation of his vaccination and medical history by a U.S.-based primary care physician. The patient's family denied history of substance abuse disorders, smoking history, high risk sexual behavior, or recent travel. He was taking no medications and had no known complaints.
The patient's primary care pediatrician was contacted who verified this medical and social history and confirmed full and timely vaccination status including for hepatitis A and B, human papillomavirus, meningococcal B, pneumococcal conjugate, varicella and influenza. Documentation was obtained from that source, and per those records he received 4 out of 5 recommended DTaP vaccinations- at ages 3 months, 5 months, 8 months, and 2 years:in Honduras, a country that successfully converted from a toxoid-based to DTaP vaccination system in 1998 as recommended by the World Health Organization and United Nations International Children's Emergency Fund, based on the similarity of side-effect profiles, marginal cost increase, and more sustained immunity. Honduras has reported rates of DTaP vaccination comparable to the U.S. since 2009. Further, the patient received a TDaP booster in the U.S. at age 15; therefore, by all accounts our patient had an up-to-date vaccination series.
Review of the patient's medical charts revealed one other admission nearly 1 year prior to the current presentation. At that time, the patient also presented in a state of unresponsiveness after he was found reportedly "sleeping" in his room by his sibling who described labored breathing. The patient presented to the hospital in a state of shock. He received atropine 0.5 mg IV bolus and fluids. The patient was sedated, intubated, and transferred to the ICU. Naloxone (Narcan) 0.4 mg IV was administered empirically, and Psychiatry Services were consulted for possible toxin ingestion. Urine and blood toxicology analysis were unremarkable (Table 1) and urine culture had no growth (Table 2). COVID-19 PCR testing from nasal swab sample collection was negative. Initial, two-draw blood cultures grew K. pneumoniae after 36 h in one bottle, and a subsequent second draw 48 h later had no growth. The patient's antibiotic treatment included four 1 g doses of third-generation cephalosporin (Ceftriaxone) b.i.d. for empiric, broad-spectrum coverage as recommended by the Infectious Disease team which also prescribed a 10-day course with 875/125 mg Amoxicillin/Clavulanate potassium (Augmentin) b.i.d. by mouth outpatient. As the patient could not be directly interviewed during his acute presentations we cannot be sure whether the patient was experiencing symptoms prior to his presentation. This is in part why the Pediatric Infectious Disease services empirically treated the patient for K. pneumo at the time of his first admission.
Further workup included a computerized tomography scan of the cranium, cervical spine, abdomen, thorax; no significant findings were reported. Cardiac electrocardiography (ECG) showed sinus tachycardia and a prolonged QTc interval of 572 ms (Figure 2). Repeat cardiac ECG showed a QTc duration of 579 ms (Figure 3). No medications associated with medication-induced QT syndrome were given during his hospitalization. A limited cardiac echocardiogram study was performed during which coronary arteries were not visualized.
The patient was extubated and discharged 4 days following his admission. He was scheduled for outpatient follow up with Pediatric Cardiology Services. A stress test performed in that setting was normal with one premature ventricular contraction. Repeat cardiac echocardiogram and CT angiogram of coronary arteries were performed showing non-structural cardiac disease. He was referred for genetic testing for further work-up of a suspected genetic cardiac abnormality due to a family-reported (but unconfirmed) paternal uncle who passed away suddenly from a heart attack at the age of 40 in Honduras. The patient did not follow up for this genetic testing, likely due to financial limitations.
Presently, testing confirmed the strain to be non-toxigenic. As per the CDC's Investigational New Drug protocol, antitoxin is only in cases of early detection of toxin-producing strains. As per official guidance, the patient was placed on droplet precaution isolation and contact-tracing of household members was conducted. All family members and close contacts were confirmed to be asymptomatic. Nasal swabs of four of the patient's nine immediate household members came back positive for C. diphtheriae, indicating carrier status. In addition to Tdap boosters, IM Penicillin G for adult, family household and close contacts were chosen for treatment after discussion between Suffolk County Department of Health and the in house Infectious Disease team. The patient's antibiotic course of piperacillin-tazobactam was extended, and cefepime 2,000 mg q.d. was added to the regime. Subsequent two-draw blood cultures on days 2 and 5 had no growth.
The patient's progress was poor; due to the extended period without protected airway and circulation, the patient suffered irreversible anoxic brain injury. His family asked that "everything be done for him" and that the Chaplain's Office, wherein representatives provide spiritual or religious support at the bedside, be involved in his case. Palliative Care Services were also consulted.
Given the patient's prior cardiac history and workup, and current presentation of cardiac arrest with pulseless electrical activity, Electrophysiology (EP) Services was consulted, and the patient was kept on telemetry monitoring as part of his ICU care. That team confirmed the likelihood of a prolonged QTc and recommended continued avoidance of exacerbating medications for which review of concomitant medications was performed. A 2D echocardiogram demonstrated left ejection fraction (LVEF) of 50-55%. The patient was not considered a candidate for any EP intervention given his poor functional status and prognosis.
On day 2 of admission, the patient deteriorated into status epilepticus and was started on 1,000 mg IV levetiracetam q.12.h. Overnight on day 2, he was noted to have a fever and continued to spike fevers daily (maximum temperature of 39.0 C) for a period of 4 days. A suprapubic catheter and feeding tube were placed. On day 9 of the patient's admission, his ventilatory status improved and a tracheostomy was performed, but he continued to produce oropharyngeal secretions requiring suctioning every few hours. Two bronchoscopies were performed; cultures of which grew ventilator-associated species- Staphylococcus aureus and Stenotrophomonas maltophilia (Table 2), for which he received 4 doses of 1,000 mg vancomycin q.d. and 12 doses of 160/800 mg trimethoprim-sulfamethoxazole q.12.h. Over 34 days he sustained a 20 lb weight loss, reaching a clinically underweight BMI of 16 despite supplementation with enteral nutrition. The patient's condition ultimately stabilized; he was discharged to a long-term care facility 45 days following his admission as per his family's wishes.