ID Case Conference

1. ID Case Conference 21 November 2007 Yvonne Ballard, MD

2. Neutropenic Fever • 63yo CM with a history of AML M2, who is admitted on 10/31 for completion of his third cycle of induction.

3. History of Chemotherapy • Diagnosed 08/07 • 08/28/07: Induced with 7+3 • 09/11/07: BM Bx showed 66% blasts • 09/14/07: Re-induced with Capizzi, completed 9/23/07 • Complicated by Neutropenic Fever, PCP Pneumonia, VRE Bacteremia, Coag neg staph Bacteremia. Access replaced three times. • 10/24 – 10/27: Re-induced with Capizzi • 10/31: Re-admitted to complete induction, completed 11/2/07

4. Hospital Course • 11/2: Completed Chemo, Neutropenic • 11/3: Loose BMs, C. diff negative • 11/8: Hct drop 25%  12%, SVT, Fevers began (high of 39.6) • Antibiotics began: Vanc, Ceftaz, Levo • 11/9: EGD – nonbleeding esophageal erosion; erythematous gastropathy • 11/11: Voriconazole added for persistent fever • 11/13: ID consulted

5. PMH: AML, M2 Diabetes Mellitus, Type 2 Hypertension Hypothyroidism DJD Umbilical Hernia Social Hx: Lives with wife Retired Occ. Etoh No Tobacco, illicits Family Hx: Mom: HTN Dad: Accidental death Medical History

6. Antibiotics: Vancomycin 1.25gm IV q8h Ceftazidime 2gm IV q8h Voriconazole 350mg po q12h Bactrim DS MWF Valtrex 500mg po bid Fluconazole 11/7 - 11/13 Levofloxacin 11/8 - 11/13 Other Meds: Atenolol 50mg daily Lipitor 5mg daily Nexium 40mg bid Finasteride 5mg daily Synthroid 75mcg daily Compazine 10mg tid Allergies: Tobramycin – Rash Medications

7. Physical Exam • VS: 36.6 133/74 70 18 98% on RA • Gen: WD, WN man comfortable in NAD • HEENT: NCAT, alopecia, Perrla, Eomi, Conj pale, sclera anicteric • OP with MMM. No overt ulcerations or mucositis. Small, discrete ulcer on the right lateral aspect of the tongue. Dentition is fair, has one dental cary. • CV: RRR, Nrml S1S2, No m/g/r • Pulm: CTA b/l, No w/r/r • Abd: Obese, soft, ND, NT, NABS • Ext: 2+ LE pitting edema, nontender • Neuro: Nonfocal • Skin: No rashes. Multiple normal appearing nevi. The pt has a moderate-sized skin tag on the left neck that appears irritated.

8. 135 103 8 72 3.7 28 0.6 Laboratory Data 9.6 1.9 3.4 10.6 <0.1 29 Urinalysis Negative 29.2 CXR: Lungs clear ANC 0.0

9. Discussion

10. Diagnosis Rothia mucilaginosa

11. Culture Data: • 11/8: Blood Culture, periph and PICC • Positive with Rothia mucilaginosa • 11/11: Repeat Blood Cultures Negative

12. Rothia mucilaginosa • Gram positive cocci • Formerly known as Stomatococcus mucilaginosus • Classified as a separate genus in the family Micrococcaceae • Normally part of flora of the human oral cavity, and upper respiratory tract • May be misidentified as Staphylococcus, Micrococcus, or Streptococcus

13. Rothia mucilaginosa • Gram positive cocci in clusters, tetrads, or pairs • Doesn’t grow on media supplemented with 5% NaCl • Non-motile, Non-spore forming • Weakly catalase positive • Strongly adherent to agar surface • Glucose fermenters • Mucoid capsule • Hydrolizes gelatine and esculin

14. Rothia mucilaginosa • Implicated recently in serious infections • Septicemia • Endocarditis • Meningitis • Pneumonia • Osteomyelitis • Peritonitis • Late prosthetic joint infections

15. Rothia mucilaginosa • Risk factors for infection include: • Indwelling venous catheter • Leukemia • Cancer • Cardiac Valvular disease • IV Drug abuse • Severe neutropenia • Mucosal damage

16. Literature Review • Considered an emerging pathogen as a cause of bacteremia in immunocompromised patients

17. Bacteremia due to Stomatococcus mucilaginosus in neutropenic patients in the setting of a cancer institute • Retrospective study of 8 patients with positive blood cultures • All neutropenic (<100 cells/mm3), All fulfilled sepsis criteria • 7/8 had mucositis • 8/8 on prophylactic Ciprofloxacin • 8/8 had Port-A-Cath in place • 5/8 resistant to quinolones • Bacteremia occurred at median time of 6.5 days of neutropenia • Review of 566 febrile neutropenic patients: • Stomatococcus the 4th most frequent gram positive bacteremia • Responsible for 5.9% of bloodstream infections Clin Microbiol Infect 2003; 9: 1068-1072.

18. Patient #1 On prophylactic fluconazole, Levofloxacin, and Acyclovir Fever, Nausea, HA, Mucositis Initial LP negative, but repeat on Day 23 showed evidence of bacterial infection, and GS positive Treated with Meropenem and intrathecal Vancomycin Total tx duration: 6 weeks Repeat cultures negative Patient #2 On prophylactic fluconazole, Levofloxacin, and Acyclovir Malaise, HA, Fever MS Δs and Fever, Day #18 LP suggestive of infection Treated with Ceftazidime, Meropenem, Rifampin, and intrathecal Vancomycin CSF never cleared Pt became comatose and eventually died 10 days later Bacterial Meningitis from Rothia mucilaginosa in Patients with Malignancy or Undergoing Hematopoietic Stem Cell Transplantation Lee et al. Pediatr Blood Cancer 2007; DOI 10.1002/pbc

19. Bacterial Meningitis from Rothia mucilaginosa in Patients with Malignancy or Undergoing Hematopoietic Stem Cell Transplantation • 18 total case reports of R. mucilaginosa meningitis • 16 occurred during stem cell transplant • 14 were neutropenic • Risk factors identified: • Profound immunocompromise • Prophylactic antibiotics • Repeated exposure to Broad spectrum antibiotics • Mucositis • Treatment • All received Vancomycin, 13/18 received 3rd gen. Ceph. • In vitro sensitivities found Rifampin to be most active drug tested, and Ampicillin was the most active β-lactam • 5/8 who received ITV survived

20. Bacteremia Caused by Rothia mucilaginosa in a Patient with Shwachman-Diamond Syndrome • 3yr old boy with SDS admitted with fever • Positive blood cultures for R.mucilaginosus • MIC90 • Rifampin, <0.016 mcg/ml • Erythromycin, <0.016 mcg/ml • Penicillin, 0.05 mcg/ml • Teicoplanin, 0.5 mcg/ml • Vancomycin, 1 mcg/ml • Linezolid 1 mcg/ml • Gentamicin, 3 mcg/ml • Tetracycline, 6 mcg/ml • Amikacin, 8 mcg/ml Vaccher, et al. Infection 2007; 35 (3): 209-210.

21. Bacteremia Caused by Rothia mucilaginosa in a Patient with Shwachman-Diamond Syndrome • Patient treated empirically with Unasyn and Netilmicin until cultures returned • Pt improved quickly • Discharged home after 5 days of Rifampin therapy (15mg/kg/day), and continued for 5 additional days • Successful recovery at 2-week follow up Vaccher, et al. Infection 2007; 35 (3): 209-210.

22. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Jan. 1995, p. 268–270. Volume 39, No 1