cases, cases, cases
TRANSCRIPT
Cases, Cases, Cases
Sara J. Blosser, Ph.D., D(ABMM)
Director, Division of Clinical Microbiology
Indiana State Department of Health
317-921-5894
“You have brains in your head. You have feet in your shoes. You can steer yourself in any direction you choose.”
- Dr. Seuss
Case 1
• Indiana hospital pharmacist is asked to consult on antibiotic selection for a post-operative ‘antibiotic cement’.
• Patient is a 22-year-old Libyan male
• Dx: Chronic osteomyelitis of the L tibia
• Patient is s/p 35 surgeries to abdomen, face, and LLE due to
injury in April 2015.
• Patient came to US in December 2015
• Has recently noticed increased drainage from LLE wound
• CT demonstrates fluid collection
• Pt is admitted and undergoes surgery for hardware
replacement
• Pt is asymptomatic (no fevers, chills, night sweats, or
diarrhea) but has significant pain in LLE
Case 1- Abbreviated Medical History
Microbiology
Surgical Wound and Bone cultures performed.
Culture results:
2+ Klebsiella pneumoniae
Drug Interpretation RUO
Ampicillin R
Amp/Sulbactam R
Aztreonam S
Cefazolin R
Cefepime R
Ceftriaxone R
Ciprofloxacin R
Colistin 4.0 µg/mL
Gentamicin S
Levofloxacin R
Meropenem R
Pip/Tazo R
Tigecycline S
Tobramycin S
Trimethoprim/Sulfa R
Any alarm bells ringing?!?!?
• Isolate is Resistant to at least one (1) agent in three (3)
classes of antibiotics: β-lactams, fluoroquinolones, and folate
pathway inhibitors
• Elevated MICs to colistin
• Susceptible to Aztreonam, Gentamicin, Tigecycline and
Tobramycin
Isolate is Resistant to at least one (1) agent in three (3) separate classes of antibiotics: β-lactams,
fluoroquinolones, and folate pathway inhibitors
MDRO
(multi-drug resistant organism)
Isolate is Resistant to Meropenem
CRE
(Carbapenem Resistant Enterobacteriaceae)
Carbapenem Resistant Enterobacteriaceae (CRE)
KPC NDM, VIM,
IMP
Non-
carbapenemase
Carbapenemase
(serine-based)
Carbapenemase
(Zinc-catalyzed)
9
Combination
of AmpC,
ESBL, porin
mutations
Isolate is susceptible to Aztreonam (monobactam) butresistant to all other tested β-lactam antibiotics
Suggestive of MBL
(metallo β-lactamase)
CRE vs. CP-CRE / CRO vs. CP-CRO
Organism
Group
Glucose Non-
Fermenters
Enterobacteriaceae
Resistance
MechanismInherent Carbapenemase
ESBL or
AmpC plus
porin loss
Carbapenemase
CRE* - - Y Y
CP-CRE - - - Y
CRO* Y Y Y Y
CP-CRO - Y - Y
CRE – Carbapenem Resistant Enterobacteriaceae
CP-CRE – Carbapenemase Producing-Carbapenem Resistant Enterobacteriaceae
CRO – Carbapenem Resistant Organism
CP-CRO – Carbapenemase Producing – Carbapenem Resistant Organism
* Indicates a ‘general description’
Woerther et al., 2013. Clin Microbiol Rev 26(4):744-58; phil.cdc.gov
Patient has a history of international travel, including invasive medical procedures.
Potential for uncommon or rare resistance determinants.
ISDH Algorithm
Day 1 – Receive isolate and subculture
Day 2* – Confirm ID and Perform PCR
• MALDI-TOF MS
• Multiplex PCR [KPC, NDM-1, OXA-48, IMP, VIM]
If Positive, report Finalized result.
• Ex. Klebsiella pneumoniae, KPC positive
If Negative – report Preliminary Negative.
Day 3 – CarbaNP on PCR negative specimens
If Positive, send to CDC for further testing.
If Negative, report out as Negative.
ISDH Algorithm
Day 1 – Receive isolate and subculture
Day 2* – Confirm ID and Perform PCR
• MALDI-TOF MS
• Multiplex PCR [KPC, NDM-1, OXA-48, IMP, VIM]
If Positive, report Finalized result.
• Ex. Klebsiella pneumoniae, KPC positive
If Negative – report Preliminary Negative.
Day 3 – CarbaNP on PCR negative specimens
If Positive, send to CDC for further testing.
If Negative, report out as Negative.
ISDH Results:
Positive for NDM-1
(New Delhi Metallo-β-lactamase)
MBLs – Impact on Clinical Care
• MBLs tend to be pan-resistant to β-lactam antibiotics, but
susceptible to aztreonam.
• New drugs like ceftazidime-avibactam, although effective
against KPC-producing organisms, do not have activity
against MBLs.
• Many MBL-producing organisms also exhibit resistance to
fluoroquinolones, aminoglycosides, and folate pathway
inhibitors.
What happened next?
• Patient was immediately put on contact precautions.
• ID was consulted:
• Diagnosis made antibiotic
management complex.
• The state (ISDH) was notified.
• Patient was discharged on minocycline,
ciprofloxacin, and amoxicillin.
• Follow up was scheduled.
https://www.cdc.gov/hai/organisms/cre/cre-toolkit/index.html
• CDR Modification Highlights Actionable Interventions
• Sets a timeline (72 hours) for investigation
• Puts a focus on acute care and
long term care
• Prevent spread by encouraging:
– Contact precautions
– CDC CRE Toolkit Use
– Screening for colonization
– Chlorhexidine bathing
In Indiana, CP-CRE is reportable for both
isolates and condition.
Long Term Care
CommunityAcute Care
https://www.cdc.gov/hai/organisms/cre/trackingcre.html
Indiana saw four (4) cases of NDM-1 in 2016.
• Odds of a patient with CP-CRE bacteremia dying within 14-
days: 4x times higher
• Higher rates of bacteremia recurrence
• More likely to receive combination antibiotic therapy
• Antibiotics given for a longer duration
CID, 2017; 64(3):257-64
Detect
Protect
Prevent
CP-CRE in Action
Conclusion:
Know your bugs! A
little knowledge can
go a long way.
Case 2
• 19-year-old female presented to the ED with s/p nausea, vomiting, fever of 1 day.
• Patient describes right upper chest pain, occasional shortness of breath, and night sweats for the past three weeks.
• Two days ago she had a cough, was diagnosed with bronchitis, given antibiotics at an Urgent Care.
• Patient states that the cough was ‘productive with yellow sputum’.
• Patient states that she has “only been able to take her antibiotic once” because of the nausea.
Abbreviated Medical History
• Tmax 104
• No sick contacts or exposure to TB.
• Has lost weight in the past week but states that this is due to poor appetite.
• Denys hemoptysis.
Imaging/Pulmonary Findings
• D0: Pneumonia RUL
• D1: Extensive pneumonitis (R>L)
• D2: Complete consolidation of RUL, RLL perihilar
opacities; extensive bilateral pneumonic infiltrates
• D5: No change, Patient Intubated
• D9: Patient Extubated, Slight improvement in RUL alveolar
consolidation and R basilar hazy density
• D10: Marked improvement in RL infiltrates
• D13: Patient discharged
Microbiology
• HIV: negative
• Hepatitis panel: negative
• Chlamydia panel: negative
• Histoplasma antigen: negative
• S. pneumoniae antigen: negative
• Leptospira serology: negative
• Coccidioides antigen: negative
• Bld Cx: negative x 2
• UA/Urine Cx: negative
• Sputum Cx – negative
• Mycoplasma IgM: negative
• Legionella antigen: negative
• Influenza Antigen: negative
• Quantiferon Gold: indeterminate (TB ruled out, sputum x 3)
• MRSA screen: negative
Chemistry
• WBCs: normal
• Polys: normal
• Platelets: normal
• Hematocrit: normal
• Creatinine: normal
Two serum specimens were collected for Hantavirus serology…
• First
• Collected 3 days after hospital admission.
• IgM – Negative
• IgG – Positive (2.08)
• Second
• Collected 11 days after hospital admission.
• IgM – Negative
• IgG – Positive (3.32)
Negative < 2.0, Positive ≥ 2.0
Spoiler! Not Hantavirus.
• No Thrombocytopenia
• Hematocrit not elevated
• No Elevated Creatinine
• Normal levels of WBC precursors
• Negative on travel history
• Negative on rodent exposure history
• IgM negative
Transmitted by inhaling the virus from mice/rat droppings or urine.
Principally carried by the Deer Mouse and Cotton Rat in the United States.
Disease caused by Hantavirus is very rare.
Hantavirus is not transmitted from person-to-person.
If people get sick from Hantavirus, they start to feel sick 1-5 weeks after exposure.
https://www.cdc.gov/hantavirus/pdf/hps_brochure.pdf
Sin Nombre Virus
• In May of 1993, outbreak of an unexplained illness in the
four corners.
• Cases presented with influenza type illness that progressed
rapidly to a more severe respiratory disease.
• Sin Nombre virus, was shown to be the cause of Hantavirus
Pulmonary Syndrome (HPS).
• The rodent reservoir was shown to be the common Deer
Mouse, Peromyscus maniculatus.
• At least 10 different strains of Sin Nombre have been
identified since that time, each associated with different
rodent species.
Indiana saw one (1) additional case of HPS in 2016.
https://www.cdc.gov/hantavirus/surveillance/reporting-state.html
Hantavirus Pulmonary Syndrome (HPS) Clinical Presentation
• Prodrome:
• Very nonspecific and short (3-5 days)
• Prodrome usually includes fever and myalgias.
• Headache, chills, dizziness, non-productive cough, nausea, vomiting,
and other gastrointestinal symptoms may also be present.
• Typical Presentation:
• Fever, tachypnea and tachycardia. Physical examination is usually
otherwise normal.
• Patients may report shortness of breath.
• Patients do not usually have a runny nose, sore
throat or rash.
HPS Clinical Presentation, continued
• Differential Diagnosis (DDx): Leptospirosis, Legionnaire's
disease, Mycoplasma, Q fever, Chlamydia, septicemic plague,
Tularemia, Coccidioidomycosis, Histoplasmosis, etc.
• Hallmarks:
• Rapid, progressive evidence of PE and hypoxia. Fatal cases
often have cardiac involvement.
• Presence of circulating immunoblasts, which appear as large
atypical lymphocytes.
• The percentage of white blood cells precursors may be as high
as 50% and atypical lymphocytes are frequently present.
• Thrombocytopenia (80% of individuals with HPS)
• Proteinuria, and mild elevations of transaminases, CPK,
amylase, and creatinine have also been reported.
So why wasn’t this Hantavirus?
Conclusion:
The serological findings were not consistent with the case
presentation.
• No Thrombocytopenia
• Hematocrit not elevated
• No Elevated Creatinine
• Normal levels of WBC precursors
• Negative on travel history
• Negative on rodent exposure history
• IgM negative
Both serum specimens sent to CDC…
Sin Nombre Hantavirus IgM = negative (x 2)
Sin Nombre Hantavirus IgG = negative (x 2)
Conclusion: When in doubt … check it out!
Thanks to …
ISDH Clinical Microbiology Division!
You all rock!
ISDH Epi
DJ Shannon
Taryn Stevens
ISDH Labs
Judy Lovchik
Kate Wainwright