ID cases

1. ID cases

2. Case 1

3. Patient identification • 13 year old male with history of pre B cell ALL, currently in relapse and on chemotherapy, admitted with acute onset fever, vomiting and headache. • 5 days prior to admission, he had a scheduled neurosurgical procedure of removal of a nonfunctioning VP shunt that was in place for congenital hydrocephalus.

4. Brief history • Patient presented to the ER with a history of fever to 102.9F that began about 4 hours prior to arrival, associated with 6-7 episodes of non-bloody, non-bilious emesis. He also complained of headache and neck pain. • A CBC done in the ER showed neutropenia and thrombocytopenia. He was given a dose of vancomycin and ceftazidime. • Although meningitis was suspected, an LP was deferred due to the recent neurosurgical procedure and thrombocytopenia. • Patient was admitted to the oncology floor for further management.

5. Past medical history 1) Pre B cell ALL diagnosed in December 2005- cancer was in remission after chemotherapy 2) Bone marrow relapse diagnosed in September 2008- started on chemotherapy. Most recent BM biopsy showed persistence of blasts. Chemotherapy was continued to attain remission in preparation for HSCT. 3) History of E. coli sepsis following induction chemotherapy in September 2008. An evaluation at that time showed pulmonary nodules. Due to neutropenic state, he was started on empiric antifungal therapy with voriconazole for suspicion of fungal etiology for the nodules.

6. Past medical history (Continued) 4) Congenital hydrocephalus-VP shunt placement at 6 months of age. Most recent evaluation showed a disconnection in the shunt with stable ventricle size. Since the presence of the shunt was a concern for infection following the planned HSCT, shunt was removed 5 days prior to admission. Shunt removal was complicated by adherence to the subdural area that caused a small portion to be broken off. The shunt removal from ventricle also was difficult. However, post op, patient did well and was discharged 3 days prior to admission.

7. Past medical history (Continued) 5) Herpes simplex virus gingivostomatitis 6) Port-a-catheter in place since 2005

8. Medications • 6-mercaptopurine • Voriconazole • Inhaled Pentamidine monthly ALLERGIES: • Sulfa drugs • Vancomycin-red man syndrome

9. Hospital course • Patient had persistent fevers of greater than 400C. Around 12 hours into admission, patient had a generalized tonic clonic seizure. The ID team was consulted for possible herpes simplex virus meningoencephalitis.

10. Epidemiological history • No history of illness in other family members. Pet dog at home. No history of travel. No history of consumption of unpasteurized dairy or undercooked meats. • Immunizations are up to date. • Father unsure of PPD placement.

11. Physical exam (immediately following seizure episode) • T-40.80C, HR-160, Saturation-97% in RA • Mildly responsive to touch, obtunded. No obvious respiratory distress. • Cracked lips; no obvious oral lesions; surgical scalp wounds are well healed. • Port-a-catheter in place; heart and lung exam normal • Abdomen soft with no hepatosplenomegaly • Skin-No rashes, no petechiae or purpura

12. Laboratory and Imaging • WBC-500 cells/mm3, Hemoglobin-9.1 g/dl, Platelets-25,000 cells/mm3 • Na-124, K-4.3, Cl-87, CO2-25 mmol/L, BUN-8, Cr-0.8 mg/dl • Urinalysis-normal • Chest radiograph-normal • CT head-Stable intra-ventricular hemorrhage (noted immediately post op). No infarction. • LP done one day into admission-CSF WBC-27, RBC-6625 cells/mm3, N-36%, L-58%, glucose-47, protein-383 mg/dl Gram stain-pending

13. Differential diagnosis • Gram positive bacteria-Streptococcus pneumoniae, Staphylococcus aureus, coagulase negative staphyloccus, Enterococcus sp, Listeria monocytogenes • Gram negative bacteria-Pseudomonas sp., Enterobacter sp., Klebsiella sp., Escherichia coli • Herpes simplex virus • Cryptococcus neoformans • Toxoplasma gondii

14. Diagnosis • Gram stain-gram positive rods (many were intra-cellular). Culture-Listeria sp

15. 13 y/o with AML CSF, Gram stain 1000X Intracytoplasmic gram positive rods Courtesy by Niaz Banaei, MD Figure 1

16. 13 y/o with AML Broth culture, Gram stain 1000X Gram positive rods Courtesy by Niaz Banaei, MD Figure 2

17. Follow up • Patient , at the time of consult , was empirically started on broad coverage-vancomycin, meropenem, acyclovir, voriconazole. • Patient had persistent uncontrolled seizures. Developed cardio-respiratory compromise. • Patient noted to have anisocoria. He had a burr hole in an attempt to decompress. • Eventually support was withdrawn.

18. Discussion • Listeriosis is caused by infection by Listeria monocytogenes, a motile, nonsporulating, facultative anaerobic gram positive bacillus. Out of the 6 species of Listeria, L. monocytogenes is the only human pathogen. Infection most often begins after ingestion of the organism in a foodborne source. • L. monocytogenes can grow in high salt and cold environments, particularly suiting it to survive and grow in processed and refrigerated foods. • Although bacteremia is a common presentation of listeria infection, the bacterium has tropism for the central nervous system, resulting in meningoencephalitis or cerebritis.

19. Discussion (continued) • The overall disease prevalence in the US is 0.7 in 100,000, however in infants is 10 in 100,000 and elderly 1.4 in 100,000. • Patients with abnormalities of T-cell mediated immunity are at particular risk. Hence, listeriosis is an important opportunistic infection in individuals on chronic steroid treatment, hematological malignancy, solid organ transplant and bone marrow transplant recipients, neonates, pregnant women and patients with AIDS. • The prognosis for cancer patients with listeria bacteremia seems to be better than that for patients with meningoencephalitis.

20. Discussion (continued) • Listeria is the fourth most common cause of bacterial meningitis after S. pneumoniae, N. meningitidis and Group B streptococcus. It is one of the 3 major causes of neonatal meningitis and is the most common cause of bacterial meningitis in patients with lymphoma, patients with organ transplants, or those receiving corticosteroid immunosuppressive therapy. • Trimethoprim-Sulfamethoxazole used primarily for Pneumocystis prophylaxis is also protective against Listeria. However, breakthrough infections are known to occur. • The preferred agent for treatment of Listeria infection is Ampicillin with Gentamicin added for synergy. Other agents such as Vancomycin and Carbapenems have in vitro activity against Listeria sp..

21. Case 2

22. HPI • 11 yo F presented to the ER with a 2 day history of abdominal pain and vomiting • Pain began at left lower quadrant and progressed to become generalized. • History of nausea and over 20 episodes of nonbloody, nonbilious emesis. • Denies diarrhea, fever, or urinary symptoms. • No medications given at home except Chamomile tea for upset stomach.

23. PMH/Meds/SH • PMH: Previously well. No history of surgeries. Menarche 1 year back. Last menstrual period was 1 month back. • Meds: None; Allergies: None • SH: Immigrated to the US 2 years back from Mexico. No history of animal exposure. Denies sexual activity.

24. Physical Examination • Wt: 44.8Kg/ 70th percentile • T- 36.4; HR-100; RR-18; BP-110/64; O2 sat-99% • Non-toxic appearing • Abdominal exam: Tenderness at right lower quadrant. Positive obturator and psoas signs. • Remainder of the exam was normal

25. Laboratories/Imaging • CBC: WBC-19.1 (90%N, 5%L), Hemoglobin-8.9, Platelets-340 • Electrolytes-Normal; Liver enzymes-Normal • Urinalysis: Sp gr >1.070, 1+ protein, negative LE and nitrites, 0-2 WBC • CT abdomen: Enlarged appendix with hyperemic mucosa with surrounding periappendiceal inflammatory stranding consistent with acute appendicitis. A calcified mesenteric lymph node was also noted. No lymphedenopathy.

26. Clinical course • Patient taken to OR for laparoscopic appendectomy • Intra-operative findings: acute appendicitis PLUS bilaterally enlarged fallopian tubes left greater than right, chronic adhesions from the omentum to the anterior abdominal wall, adhesions from the anterior surface of the liver to the anterior abdominal wall and some yellow plaques on the liver surface.

27. Clinical course • Gynecology consultation to perform intra-operative examination. • Findings and management: dilated, hyperemic appearance of the fallopian tubes, with the fluid within the tubes appearing to be less purulent than would be the appearance of a typical pyosalpinx. A pelvic examination revealed copious yellow vaginal discharge, a nulliparous cervix, and fimbriated hymen with no evidence of trauma. Cervical specimens were sent for Gonorrhea and Chlamydia nucleic acid amplification tests (NAAT) and cultures.

28. Differential Diagnoses 1. Fitz-Hugh-Curtis and pelvic inflammatory disease due to sexually transmitted agent 2. Abdominal/pelvic Mycobacterium disease 3. Peritonitis from ruptured appendicitis 4. Acute Yersinia sp. infection 5. Inflammatory bowel disease 6. Celiac disease

29. Diagnosis • PPD placed and positive at >25mm at 40 hours. • Quantiferon-Gold positive. • Gonorrhea and Chlamydia NAAT negative. • Chest x-ray negative for active or past evidence of tuberculosis. • On review of history again, family has a history of consumption of unpasteurized cheese.

30. Diagnosis • Endometrial biopsy was eventually obtained for microbiologic diagnosis. • Pathology- proliferative endometrium with granulomatous inflammation and rare acid-fast-bacilli • Microbiology- Cultures confirmed Mycobacterium bovis. Susceptibility testing showed sensitivity to INH, Rifampin and Ethambutol and resistance to Pyrazinamide.

31. Pathology slide of the endometrial tissue biopsy Proliferative phase endometrium with granulomatous inflammation, H&E stain, at 600X (Courtesy of Lisa Pate, MD)

32. Pathology slide of the endometrial tissue biopsy Proliferative phase endometrium with rare acid-fast bacilli (arrow), AFB stain, at 1000X (Courtesy of Lisa Pate, MD)

33. Treatment and follow up • Treated with INH and Rifampin for 1 year. +Ethambutol for first 2 months • Patient did very well throughout therapy. • Follow up laparoscopy after 2 months of end of therapy showed normal fallopian tubes and ovaries with minimal adhesions of cul-de-sac and a few plaques on the liver.

34. Mycobacterium bovis • One of the species of the Mycobacterium tuberculosis complex • Tuberculosis due to M. bovis is a zoonosis • M. bovis primarily infects cattle and the pathogen is transmitted to humans by consumption of unpasteurized dairy products.

35. Mycobacterium bovis- Epidemiology • Rare in developed countries due to pasteurization of dairy and testing and culling of infected cattle. • Higher burden in developing world but due to inadequate resources for diagnosis, number of affected humans is unknown. • Accurate diagnosis is important for appropriate choice of anti-tuberculosis medications and length of therapy since M. bovisis intrinsically resistant to pyrazinamide.

36. Mycobacterium bovis - Clinical aspects • Manifests as primary infection and reactivation. • Can cause pulmonary, extrapulmonary and disseminated disease. • Extrapulmonary infection (Gastrointestinal tract, peritoneum, genito-urinary tract) is more common as the infection is usually acquired by ingestion of the bacilli.

37. Mycobacterium bovis- Diagnosis and Treatment • Direct microscopy to visualize granulomatous inflammation and acid-fast bacilli • Isolation in cultures which can take 3-6 weeks and identification of species of the Mycobacterium tuberculosis complex by PCR. • M. bovis is intrinsically resistant to Pyrazinamide. • Therapy for M. bovis is usually longer since pyrazinamide cannot be used (9-12 month regimen)

38. Case 3

39. HPI • GR is a 11 month IM with h/o ‘noisy breathing’ worse when lying supine and difficulty feeding for 3-4 months. • 3-4 days PTA had worsening stridor. • CXR showed possible mass at trachea. • Exposure history significant for visit to India at 3 months of age and a grandmother with chronic cough.

40. HPI cont’d • Underwent laryngoscopy, bronchoscopy and esophagoscopy. • Failed extubation following procedure and remained intubated for about 10 days. • Underwent Chest/Abdomen CT scan that showed multiple hilar and mediastinal LNs and hypodense lesions in spleen.

46. Hospital course • Differentials included oncological process (such as lymphoma/neuroblastoma) and infectious process. • ID team consulted. PPD placed as TB was high on the differential • PPD positive at 15mm • Patient underwent hilar LN biopsy and cultures grew Mycobacterium tuberculosis.

47. Culture and sensitivity

48. Management • CSF studies normal. CT head-normal • INH/Rif/Pyr/Etm was started • Completed 9 months of treatment for disseminated Mycobacterium tuberculosis infection.

49. Case 4

50. History of Present Illness • An 8 year-old girl developed fever ten days after family camping trip • Five days of fever to 102-104 • Diffuse headache, nausea, and two episodes of non-bloody, non-bilious emesis • History of three small “insect bites” on abdomen, which quickly resolved • No photophobia, phonophobia, or neck stiffness • No sore throat, cough, conjunctivitis, diarrhea, arthralgias, or myalgias • Fevers resolved on the fifth day of illness • Afebrile for 5 days • Recurrent fever prompted outpatient evaluation.