Sex: M
Vaccine: DTAP, DTAP, DTAP, DTAP, TDAP
Symptoms: Mydriasis, Nitrite urine absent, Opiates negative, Oropharyngeal suctioning, Protein total
Clinical narrative: C. diphtheriae strain infection; unconscious/ state of unresponsiveness; cardiac arrest; lateral wall ischemia; sepsis; leukocytosis; klebsiella pneumoniae; labored breathing; shock; non-structural cardiac disease; anoxic brain injury; status epilepticus; fever; Staphylococcus aureus; Stenotrophomonas maltophilia; weight loss; sinus tachycardia; premature ventricular contraction; C. diphtheriae strain infection; This serious case was reported in a literature article and described the occurrence of vaccination failure in a 18-year-old male patient who received DTPa (Diphtheria tetanus acellular pertussis) for prophylaxis.   Co-suspect products included DTPa (Diphtheria tetanus acellular pertussis) for prophylaxis, DTPa (Diphtheria tetanus acellular pertussis) for prophylaxis, DTPa (Diphtheria tetanus acellular pertussis) for prophylaxis and DTPa (Reduced antigen) (Tdap Vaccine) for prophylaxis.   Previously administered products included Hepatitis A and Hepatitis B, human papillomavirus, meningococcal B, pneumococcal, varicella and Influenza. Additional patient notes included patient's family denied history of substance abuse disorders, smoking history, high risk sexual behavior, or recent travel, was not taking any medications and had no known complaints. Family history included heart attack (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).   On an unknown date, the patient received Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis and Tdap Vaccine. On an unknown date, an unknown time after receiving Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis and Tdap Vaccine, the patient experienced vaccination failure (Verbatim: C. diphtheriae strain infection) (serious criteria GSK medically significant), corynebacterium diphtheriae infection (Verbatim: C. diphtheriae strain infection) (serious criteria hospitalization and GSK medically significant), unconscious (Verbatim: unconscious/ state of unresponsiveness) (serious criteria hospitalization, GSK medically significant and clinically significant/intervention required), cardiac arrest (Verbatim: cardiac arrest) (serious criteria hospitalization, GSK medically significant and clinically significant/intervention required), ischemia (Verbatim: lateral wall ischemia) (serious criteria hospitalization), sepsis (Verbatim: sepsis) (serious criteria hospitalization and GSK medically significant), leukocytosis (Verbatim: leukocytosis) (serious criteria hospitalization), klebsiella pneumoniae infection (Verbatim: klebsiella pneumoniae) (serious criteria hospitalization), labored breathing (Verbatim: labored breathing) (serious criteria hospitalization and clinically significant/intervention required), shock (Verbatim: shock) (serious criteria hospitalization, GSK medically significant and clinically significant/intervention required), heart disorder (Verbatim: non-structural cardiac disease) (serious criteria hospitalization), anoxic brain damage (Verbatim: anoxic brain injury) (serious criteria hospitalization and GSK medically significant), status epilepticus (Verbatim: status epilepticus) (serious criteria hospitalization and GSK medically significant), fever (Verbatim: fever) (serious criteria hospitalization), staphylococcus aureus infection (Verbatim: Staphylococcus aureus) (serious criteria hospitalization), stenotrophomonas maltophilia infection (Verbatim: Stenotrophomonas maltophilia) (serious criteria hospitalization and GSK medically significant), weight loss (Verbatim: weight loss) (serious criteria hospitalization), sinus tachycardia (Verbatim: sinus tachycardia) (serious criteria hospitalization) and premature ventricular contractions (Verbatim: premature ventricular contraction) (serious criteria hospitalization). The patient was treated with epinephrine, piperacillin-tazobactam, vancomycin, atropine, naloxone hydrochloride (Narcan), ceftriaxone, amoxicillin + clavulanic acid (Augmentin), cefepime, levetiracetam and sulfamethoxazole + trimethoprim (Trimethoprim-Sulfamethoxazole). The outcome of the vaccination failure was unknown and the outcome of the corynebacterium diphtheriae infection, unconscious, cardiac arrest, ischemia, sepsis, leukocytosis, klebsiella pneumoniae infection, labored breathing, shock, heart disorder, anoxic brain damage, status epilepticus, fever, staphylococcus aureus infection, stenotrophomonas maltophilia infection, weight loss, sinus tachycardia and premature ventricular contractions were resolving.   The reporter considered the vaccination failure, corynebacterium diphtheriae infection, unconscious, cardiac arrest, ischemia, sepsis, leukocytosis, heart disorder, anoxic brain damage, status epilepticus, fever, weight loss, sinus tachycardia and premature ventricular contractions to be related to Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis and Tdap Vaccine. It was unknown if the reporter considered the klebsiella pneumoniae infection, labored breathing, shock, staphylococcus aureus infection and stenotrophomonas maltophilia infection to be related to Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis and Tdap Vaccine.     The company considered the vaccination failure, corynebacterium diphtheriae infection, unconscious, cardiac arrest, ischemia, sepsis, leukocytosis, heart disorder, anoxic brain damage, status epilepticus, fever, weight loss, sinus tachycardia and premature ventricular contractions to be related to Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis and Tdap Vaccine. It was unknown if the company considered the klebsiella pneumoniae infection, labored breathing, shock, staphylococcus aureus infection and stenotrophomonas maltophilia infection to be related to Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis, Diphtheria tetanus acellular pertussis and Tdap Vaccine.   Additional Information: GSK Receipt Date: 8-May-2023 The patient presented to the Emergency Department (ED). The patient was unconscious for approximately 10 minutes during which time the patient did not receive cardiopulmonary resuscitation (CPR). Upon arrival, the patient 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. Vital signs, laboratory values, including a toxicology screen, and urinalysis were all unremarkable; urine culture had no growth. 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.hour. 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 (Corynebacterium diphtheriae) (anaerobic bottles) and Klebsiella pneumoniae (both aerobic and anaerobic bottles) as identified with polymerase chain reaction (PCR) analysis. Patient samples were shipped overnight for confirmatory testing. 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 ascertained. The patient was reported to have immigrated to this country 3 years prior at the age of 15. The patient attended public high school, which requires by State Public Health law, documentation of the patient's vaccination and medical history by a specific country based primary care physician. The patient's family denied history of substance abuse disorders, smoking history, high risk sexual behavior, or recent travel. The patient 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 the patient received 4 out of 5 recommended DTaP vaccinations- at ages 3 months, 5 months, 8 months, and 2 years in another country. Further, the patient received a TDaP booster in the this country 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 the patient was found reportedly "sleeping" in the room by his sibling who described labored breathing. The patient presented to the hospital in a state of shock. The patient received atropine 0.5 mg intravenous (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 and urine culture had no growth. COVID-19 PCR testing from nasal swab sample collection was negative. Initial, two-draw blood cultures grew K. pneumoniae after 36 hour in one bottle, and a subsequent second draw 48 hour 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 was in part why the Pediatric Infectious Disease services empirically treated the patient for K. pneumo at the time of the 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. Repeat cardiac ECG showed a QTc duration of 579 ms. 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. The patient 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. The patient 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. The patient did not follow up for this genetic testing, likely due to financial limitations. Progression and resolution of the case Presently, testing confirmed the strain to be non-toxigenic. 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, Intramuscular Penicillin G for adult, family household and close contacts were chosen for treatment. 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. 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 percent. 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.hour. Overnight on day 2, the patient was noted to have a fever and continued to spike fevers daily (maximum temperature of 39.0 degree Celsius) for a period of 4 days. A suprapubic catheter and feeding tube were placed. On day 9 of the patient's admission, the ventilatory status improved and a tracheostomy was performed, but the patient 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, for which the patient received 4 doses of 1,000 mg vancomycin q.d. and 12 doses of 160/800 mg trimethoprim-sulfamethoxazole q.12.hour. Over 34 days the patient sustained a 20-pound weight loss, reaching a clinically underweight BMI of 16 despite supplementation with enteral nutrition. The patient's condition ultimately stabilized and was discharged to a long-term care facility 45 days following the admission as per the family's wishes. The author hoped practitioners would consider at which points in the healthcare system efforts could have ameliorated a better outcome and the lingering future threat of disease resulting from infection with non-toxigenic forms of C. diphtheriae in vaccinated populations. The article corresponding to this case is not available for regulatory submission due to copyright restriction.