ID Case Conference 21 November 2007 Yvonne Ballard, MD

ID Case ConferenceID Case Conference

21 November 200721 November 2007

Yvonne Ballard, MD Yvonne Ballard, MD

Neutropenic FeverNeutropenic Fever

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

History of ChemotherapyHistory of Chemotherapy Diagnosed 08/07Diagnosed 08/07 08/28/07: Induced with 7+308/28/07: Induced with 7+3 09/11/07: BM Bx showed 66% blasts09/11/07: BM Bx showed 66% blasts 09/14/07: Re-induced with Capizzi, completed 09/14/07: Re-induced with Capizzi, completed

9/23/079/23/07– Complicated by Neutropenic Fever, PCP Pneumonia, Complicated by Neutropenic Fever, PCP Pneumonia,

VRE Bacteremia, Coag neg staph Bacteremia. Access VRE Bacteremia, Coag neg staph Bacteremia. Access replaced three times.replaced three times.

10/24 – 10/27: Re-induced with Capizzi10/24 – 10/27: Re-induced with Capizzi 10/31: Re-admitted to complete induction, 10/31: Re-admitted to complete induction,

completed 11/2/07 completed 11/2/07

Hospital CourseHospital Course

11/2: Completed Chemo, Neutropenic11/2: Completed Chemo, Neutropenic 11/3: Loose BMs, C. diff negative11/3: Loose BMs, C. diff negative 11/8: Hct drop 25% 11/8: Hct drop 25% 12%, SVT, Fevers 12%, SVT, Fevers

began (high of 39.6)began (high of 39.6)– Antibiotics began: Vanc, Ceftaz, LevoAntibiotics began: Vanc, Ceftaz, Levo

11/9: EGD – nonbleeding esophageal 11/9: EGD – nonbleeding esophageal erosion; erythematous gastropathyerosion; erythematous gastropathy

11/11: Voriconazole added for persistent fever11/11: Voriconazole added for persistent fever 11/13: ID consulted11/13: ID consulted

Medical HistoryMedical History

PMH:PMH:– AML, M2AML, M2– Diabetes Mellitus, Diabetes Mellitus,

Type 2Type 2– HypertensionHypertension– HypothyroidismHypothyroidism– DJDDJD– Umbilical HerniaUmbilical Hernia

Social Hx:Social Hx:– Lives with wifeLives with wife– RetiredRetired– Occ. EtohOcc. Etoh– No Tobacco, illicitsNo Tobacco, illicits

Family Hx:Family Hx:– Mom: HTNMom: HTN– Dad: Accidental Dad: Accidental

deathdeath

MedicationsMedications

Antibiotics: Antibiotics: – Vancomycin 1.25gm IV Vancomycin 1.25gm IV

q8h q8h – Ceftazidime 2gm IV q8hCeftazidime 2gm IV q8h– Voriconazole 350mg po Voriconazole 350mg po

q12h q12h – Bactrim DS MWF Bactrim DS MWF – Valtrex 500mg po bid Valtrex 500mg po bid

Fluconazole 11/7 - 11/13 Fluconazole 11/7 - 11/13 Levofloxacin 11/8 - 11/13Levofloxacin 11/8 - 11/13

Other Meds: Other Meds: – Atenolol 50mg dailyAtenolol 50mg daily– Lipitor 5mg daily Lipitor 5mg daily – Nexium 40mg bidNexium 40mg bid– Finasteride 5mg daily Finasteride 5mg daily – Synthroid 75mcg daily Synthroid 75mcg daily – Compazine 10mg tidCompazine 10mg tid

Allergies: Tobramycin – Allergies: Tobramycin – RashRash

Physical ExamPhysical Exam VS: 36.6 133/74 70 18 98% on RAVS: 36.6 133/74 70 18 98% on RA Gen: WD, WN man comfortable in NADGen: WD, WN man comfortable in NAD HEENT: NCAT, alopecia, Perrla, Eomi, Conj pale, sclera anictericHEENT: NCAT, alopecia, Perrla, Eomi, Conj pale, sclera anicteric OP with MMM. No overt ulcerations or mucositis. Small, discrete ulcer 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 on the right lateral aspect of the tongue. Dentition is fair, has one dental cary.cary.

CV: RRR, Nrml S1S2, No m/g/rCV: RRR, Nrml S1S2, No m/g/r Pulm: CTA b/l, No w/r/rPulm: CTA b/l, No w/r/r Abd: Obese, soft, ND, NT, NABSAbd: Obese, soft, ND, NT, NABS Ext: 2+ LE pitting edema, nontenderExt: 2+ LE pitting edema, nontender Neuro: NonfocalNeuro: Nonfocal Skin: No rashes. Multiple normal appearing nevi. The pt has a Skin: No rashes. Multiple normal appearing nevi. The pt has a

moderate-sized skin tag on the left neck that appears irritated.moderate-sized skin tag on the left neck that appears irritated.

Laboratory DataLaboratory Data

135

3.7

103

28

8

0.672

<0.1 29

3.4

1.9

9.6

ANC 0.0

29.2

10.6Urinalysis Negative

CXR: Lungs clear

DiscussionDiscussion

DiagnosisDiagnosis

Rothia mucilaginosaRothia mucilaginosa

Culture Data:Culture Data:

11/8: Blood Culture, periph and PICC11/8: Blood Culture, periph and PICC– Positive with Positive with Rothia mucilaginosaRothia mucilaginosa

11/11: Repeat Blood Cultures Negative11/11: Repeat Blood Cultures Negative


Gram positive cocciGram positive cocci Formerly known as Formerly known as Stomatococcus Stomatococcus

mucilaginosusmucilaginosus Classified as a separate genus in the family Classified as a separate genus in the family

MicrococcaceaeMicrococcaceae Normally part of flora of the human oral Normally part of flora of the human oral

cavity, and upper respiratory tractcavity, and upper respiratory tract May be misidentified as May be misidentified as StaphylococcusStaphylococcus, ,

MicrococcusMicrococcus, or , or StreptococcusStreptococcus

Rothia mucilaginosaRothia mucilaginosa Gram positive cocci in clusters, tetrads, or pairsGram positive cocci in clusters, tetrads, or pairs Doesn’t grow on media supplemented with 5% Doesn’t grow on media supplemented with 5%

NaClNaCl Non-motile, Non-spore formingNon-motile, Non-spore forming Weakly catalase positiveWeakly catalase positive Strongly adherent to agar surfaceStrongly adherent to agar surface Glucose fermentersGlucose fermenters Mucoid capsuleMucoid capsule Hydrolizes gelatine and esculinHydrolizes gelatine and esculin


Implicated recently in serious infectionsImplicated recently in serious infections– SepticemiaSepticemia– EndocarditisEndocarditis– MeningitisMeningitis– PneumoniaPneumonia– OsteomyelitisOsteomyelitis– PeritonitisPeritonitis– Late prosthetic joint infectionsLate prosthetic joint infections


Risk factors for infection include:Risk factors for infection include:– Indwelling venous catheterIndwelling venous catheter– LeukemiaLeukemia– CancerCancer– Cardiac Valvular diseaseCardiac Valvular disease– IV Drug abuseIV Drug abuse– Severe neutropeniaSevere neutropenia

» Mucosal damageMucosal damage

Literature ReviewLiterature Review

Considered an emerging pathogen as a Considered an emerging pathogen as a cause of bacteremia in cause of bacteremia in immunocompromised patientsimmunocompromised patients

Bacteremia due to Bacteremia due to Stomatococcus mucilaginosusStomatococcus mucilaginosus in in neutropenic patients in the setting of a cancer instituteneutropenic patients in the setting of a cancer institute

Retrospective study of 8 patients with positive blood culturesRetrospective study of 8 patients with positive blood cultures

– All neutropenic (<100 cells/mm3), All fulfilled sepsis criteriaAll neutropenic (<100 cells/mm3), All fulfilled sepsis criteria

– 7/8 had mucositis7/8 had mucositis

– 8/8 on prophylactic Ciprofloxacin8/8 on prophylactic Ciprofloxacin

– 8/8 had Port-A-Cath in place8/8 had Port-A-Cath in place

– 5/8 resistant to quinolones5/8 resistant to quinolones

– Bacteremia occurred at median time of 6.5 days of neutropeniaBacteremia occurred at median time of 6.5 days of neutropenia

Review of 566 febrile neutropenic patients:Review of 566 febrile neutropenic patients:

– Stomatococcus the 4Stomatococcus the 4thth most frequent gram positive bacteremia most frequent gram positive bacteremia

– Responsible for 5.9% of bloodstream infectionsResponsible for 5.9% of bloodstream infections

Clin Microbiol Infect 2003; 9: 1068-1072.

Bacterial Meningitis from Bacterial Meningitis from Rothia mucilaginosaRothia mucilaginosa in Patients with in Patients with Malignancy or Undergoing Hematopoietic Stem Cell TransplantationMalignancy or Undergoing Hematopoietic Stem Cell Transplantation

Patient #1Patient #1– On prophylactic fluconazole, On prophylactic fluconazole,

Levofloxacin, and AcyclovirLevofloxacin, and Acyclovir

– Fever, Nausea, HA, Fever, Nausea, HA, MucositisMucositis

– Initial LP negative, but Initial LP negative, but repeat on Day 23 showed repeat on Day 23 showed evidence of bacterial evidence of bacterial infection, and GS positiveinfection, and GS positive

– Treated with Meropenem Treated with Meropenem and intrathecal Vancomycinand intrathecal Vancomycin

– Total tx duration: 6 weeksTotal tx duration: 6 weeks

– Repeat cultures negativeRepeat cultures negative

Patient #2Patient #2– On prophylactic fluconazole, On prophylactic fluconazole,

Levofloxacin, and AcyclovirLevofloxacin, and Acyclovir

– Malaise, HA, FeverMalaise, HA, Fever

– MS MS ΔΔs and Fever, Day #18s and Fever, Day #18

– LP suggestive of infectionLP suggestive of infection

– Treated with Ceftazidime, Treated with Ceftazidime, Meropenem, Rifampin, and Meropenem, Rifampin, and intrathecal Vancomycinintrathecal Vancomycin

– CSF never clearedCSF never cleared

– Pt became comatose and Pt became comatose and eventually died 10 days eventually died 10 days laterlater

Lee et al. Pediatr Blood Cancer 2007; DOI 10.1002/pbc

Bacterial Meningitis from Bacterial Meningitis from Rothia mucilaginosaRothia mucilaginosa in Patients with in Patients with Malignancy or Undergoing Hematopoietic Stem Cell TransplantationMalignancy or Undergoing Hematopoietic Stem Cell Transplantation

18 total case reports of 18 total case reports of R. mucilaginosaR. mucilaginosa meningitis meningitis– 16 occurred during stem cell transplant16 occurred during stem cell transplant– 14 were neutropenic14 were neutropenic

Risk factors identified:Risk factors identified:– Profound immunocompromiseProfound immunocompromise– Prophylactic antibioticsProphylactic antibiotics– Repeated exposure to Broad spectrum antibioticsRepeated exposure to Broad spectrum antibiotics– MucositisMucositis

TreatmentTreatment– All received Vancomycin, 13/18 received 3All received Vancomycin, 13/18 received 3rdrd gen. Ceph. gen. Ceph.– In vitro sensitivities found Rifampin to be most active drug In vitro sensitivities found Rifampin to be most active drug

tested, and Ampicillin was the most active tested, and Ampicillin was the most active ββ-lactam-lactam– 5/8 who received ITV survived5/8 who received ITV survived

Bacteremia Caused by Bacteremia Caused by Rothia mucilaginosaRothia mucilaginosa in a Patient with in a Patient with Shwachman-Diamond SyndromeShwachman-Diamond Syndrome

3yr old boy with SDS admitted with fever 3yr old boy with SDS admitted with fever Positive blood cultures for R.mucilaginosusPositive blood cultures for R.mucilaginosus MICMIC9090

– Rifampin, <0.016 mcg/mlRifampin, <0.016 mcg/ml– Erythromycin, <0.016 mcg/mlErythromycin, <0.016 mcg/ml– Penicillin, 0.05 mcg/mlPenicillin, 0.05 mcg/ml– Teicoplanin, 0.5 mcg/mlTeicoplanin, 0.5 mcg/ml– Vancomycin, 1 mcg/mlVancomycin, 1 mcg/ml– Linezolid 1 mcg/mlLinezolid 1 mcg/ml– Gentamicin, 3 mcg/mlGentamicin, 3 mcg/ml– Tetracycline, 6 mcg/mlTetracycline, 6 mcg/ml– Amikacin, 8 mcg/mlAmikacin, 8 mcg/ml

Vaccher, et al. Infection 2007; 35 (3): 209-210.

Bacteremia Caused by Bacteremia Caused by Rothia mucilaginosaRothia mucilaginosa in a Patient with in a Patient with Shwachman-Diamond SyndromeShwachman-Diamond Syndrome

Patient treated empirically with Unasyn Patient treated empirically with Unasyn and Netilmicin until cultures returnedand Netilmicin until cultures returned

Pt improved quicklyPt improved quickly Discharged home after 5 days of Discharged home after 5 days of

Rifampin therapy (15mg/kg/day), and Rifampin therapy (15mg/kg/day), and continued for 5 additional dayscontinued for 5 additional days

Successful recovery at 2-week follow upSuccessful recovery at 2-week follow up

Vaccher, et al. Infection 2007; 35 (3): 209-210.

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

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ID Case Conference 21 November 2007 Yvonne Ballard, MD