Pimpawan Boapimp, MD

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INFECTIOUS DISEASES CASE CONFERENCE
Pimpawan Boapimp, MD Wake Forest Baptist Medical
Center May 10, 2004
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PI 43 y/o WF with PMH of COPD presented
with fever, cough, SOB CXR showed bilat lower
lobes infiltrate was admitted for 8 days,
treated for pneumonia with Levaquin
gentamicin and sent home with Levaquin PCN SOB
got worse assoc. with DOE, orthopnea

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• 2 days later was seen in OPD, TTE done
• TTE- severe MR, vegetation on MV and AV
• BC grew fastidious streptococcus viridans
• Readmitted for GPC bacteremia and IE
• OSH called ID at Baptist for a brief
  consultation. Ceftriaxone and gentamicin
• were started

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PMH

• Denies recent tooth pain, dental abscesses,
• dental work
• Had UGIB several months ago
• Depression
• HTN, fibromyalgia, COPD, anemia, MVP
• NKDA
• quit smoking one week PTA
• ROS DOE , otherwise negative

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• transferred to Baptist Med Ctr
• TEE done on admission showed
• - LAE, severe AR, MR
• - vegetation on MV, AV
• BC at our hospital no growth
• underwent AVR and MVR (porcine)

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• tissue from MV and AV
• -Gram stain no organism
• -C/S no growth
• no complication after Sx
• ID was consulted for ATBs management

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Physical Examination

• VS T 98.6 F P 64 RR 18 BP 101/57
• PO 97 2LNC
• GA AO x 3, afebrile, NAD
• HEENT PERRLA, EOMI
• CHEST decrease BS bases,
• Sx wound-healing well
• HEART RSR, valve click

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Physical Examination

• ABD soft, not tender, BS ,
• no organomegaly
• EXT no edema
• NS no focal deficit
• SKIN no rash
• IV PICC at LUE

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Diagnostic Data

• CBC WBC 15.6 Hb 9.8 Hct 29.8 Plt 189
• BMP WNL , LFT WNL
• BNP 862
• UA -WNL
• CXR
• COPD with bilateral pleural effusions and
  bibasilar aeration disturbance which could
  reflect pneumonia

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• C/S from OSH grew fastidious S. viridans
• MICs not available
• ATBs was changed to PCN and C/W gentamicin
• clinically stable, no F/C, no signs of CHF

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BC from OSH

• Streptococcus viridans group
• nutritionally deficient streptococci
• The isolate is too fastidious for susceptibility
  studies.

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• Facklam R.What happened to the streptococci
  overview of taxonomic and nomenclature changes.
  Clin Microbiol Rev. 2002 Oct15(4)613-30.
  Streptococcus Laboratory, Centers for Disease
  Control and Prevention

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• Brouqui P, Raoult D.Endocarditis due to rare
  and fastidious bacteria.
• Clin Microbiol Rev. 2001 Jan14(1)177-207.

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Nutritionally variant streptococci NVS

• originally described in 1961 as a new type of
  viridans streptococci
• In 1989, Bouvet et al. demonstrated 2 species
  within the NVS, S. adjacens and S. defectives
• In 1995, using the 16S rRNA gene sequencing NVS,
  Kawamura et al. proposed a new genus, __________

Abiotrophia
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Nutritionally variant streptococci NVS

• 4 species of Abiotrophia
• A. defectiva
• A. adiacens
• A. balaenopterae
• A. elegans
• In 2000, Collins and Lawson proposed a new genus,
  Granulicatella, to reclassify
• Abiotrophia

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Abiotrophia spp.

• Abiotrophia consisted of only A. defectiva
• fastidious organisms
• streptococcal L-forms
• required metabolic products of other bacteria for
  growth

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Abiotrophia spp.

• Numerous synonyms
• -satelliting Streptococcus
• -thiol-requiring Streptococcus
• -vitamin B6-dependant Streptococcus
• -pyridoxal-dependent Streptococcus
• -symbiotic Streptococcus
• -nutritionally variant streptococci

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Abiotrophia spp.

• More than 100 cases of Abiotrophia endocarditis
  reported
• cause 5 to 6 of all cases of streptococcal
  endocarditis
• 4.3 of cases of streptococcal IE caused by
  Abiotrophia spp.
• may be underestimated because they are fastidious
  organisms, it is likely that most cases are
  misdiagnosed as culture-negative IE

Brouqui P, Raoult D. Endocarditis due to rare and
fastidious bacteria. Clin Microbiol Rev. 2001
Jan14(1)177-207.
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Abiotrophia spp.

• Preexisting heart disease is found in 90 of
  patients
• known cardiac murmur - most common finding
• prosthetic heart valves -only 10 of patients

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Abiotrophia spp.

• normal oral, genitourinary, and intestinal floras
• Endocarditis usually occurs as a result of
  bacteremia in patients with an underlying valve
  injury.
• slow and indolent course of IE
• With progression of the disease, complications
  such as septic arthritis are observed.

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Abiotrophia spp.

• The classical peripheral manifestations of
  endocarditis, including digital clubbing,
  petechiae, and Osler nodes, are not frequently
  observed.
• But embolization occurs in one-third of patients
• Affects the aortic and mitral valves with similar
  frequency (13 and 11, respectively)

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Abiotrophia spp.

• CHF may be the first manifestation in some
  late-recognized cases.

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Abiotrophia spp.

• Culture
• cysteine was added into culture media
• can be detected in routine BC in 2 or 3 days
• Fresh human blood enhances the recovery of these
  bacteria

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Abiotrophia spp.

• In contrast, subcultures usually require
  supplementation of blood agar with
• -pyridoxal hydrochloride (10 to 100 mg/L)
• -or L-cysteine (100 mg/L)
• under an aerobic or anaerobic atmosphere

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Abiotrophia spp.

• Alternatively, use a coagulase-positive
  Staphylococcus as helper to induce satellite
  growth
• Tiny alpha-hemolytic or nonhemolytic colonies
  appear after 18 h either alone or as satelliting
  colonies around a helper strain
• also found to form satellite colonies around
  Enterobacteriaceae and other streptococci

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Abiotrophia spp.

• or use liquid broth supplemented with pyridoxal
  hydrochloride or cysteine
• Microscopic examination
• -morphological pleiomorphism
• cocci, coccobacilli, rod-shaped,
  globular (bulbous) bacteria
• -variable Gram staining
• differentiated from viridans streptococci by
  production of pyrrolidone arylamidase

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Abiotrophia spp.

• Morbidity and mortality exceed those of the other
  forms of viridans streptococcal and enterococcal
  endocarditis
• Therapy results in a bacteriological failure in
  41 of patients in spite of the in vitro
  bactericidal effects of antibiotics

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Abiotrophia spp.

• 27 of patients require prosthetic valve
  replacement
• 17 to 20 of patients die due to uncontrolled CHF
  or major systemic emboli
• More than 30 of strains of Abiotrophia are
  resistant to 0.12 mg of penicillin per liter

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Abiotrophia spp.

• In a rabbit model of IE
• PCN gentamicin more effective than PCN alone
• Vancomycin alone is as effective as
• PCN gentamicin in a rabbit model
• (vancomycin is not bactericidal)
• Henry NK, et al. Antimicrobial therapy of
  experimental endocarditis caused by nutritionally
  variant viridans group streptococci.Antimicrob
  Agents Chemother. 1986 Sep30(3)465-7.  

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Granulicatella spp.

• some of Abiotrophia species were phylogenetically
  distinct from each other
• New genus- Granulicatella spp.
• -G. adiacens
• -G. elegans
• -G. balaenopterae
• All species except G. balaenopterae have been
  isolated from human infections

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Treatment

• Sanford Guide
• S. viridans, S. bovis with PCN G MIC 0.1 to
  strep (MBC 32-fold MIC)
• PCN G 18 mU/d x 4 wks PLUS gentamicin 1 mg/kg q 8
  hrs x 2 wks
• Alternative
• Cefazolin (not IgE-mediated PCN allergy)
• or Vancomycin x 4 wks

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• NVS are frequently resistant to penicillin, and
  resistance to extended-spectrum cephalosporins
  and newer fluoroquinolones
• Tuohy MJ, Procop GW, Washington JA.
  Antimicrobial susceptibility of Abiotrophia
  adiacens and Abiotrophia defectiva. Diagn
  Microbiol Infect Dis 2000 38189 91.

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• Liao CH, et al.
• Nutritionally variant streptococcal infections
  at a University Hospital in Taiwan disease
  emergence and high prevalence of beta-lactam and
  macrolide resistance. Clin Infect Dis. 2004 Feb
  138(3)452-5. Epub 2004 Jan

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• 28 pts with NVS infection
• 9 pts had IE
• 9 pts had primary bacteremia
• IE pts were treated with PCN or other ß-lactams
  (ampicillin, ampicillin-sulbactam,
  amoxicillin-clavulanate, cefazolin, cefmetazole,
  ceftriaxone, or meropenem) PLUS gentamicin or a
  glycopeptide (vancomycin or teicoplanin) for 4 -
  6 wks

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• All of the isolates were susceptible to
  vancomycin, quinupristin-dalfopristin, linezolid,
  levofloxacin, moxifloxacin, and gatifoxacin.

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• 50 of isolates had intermediate susceptibility
  to penicillin (i.e., MICs of 0.25- 2 µg/mL)
• 33 were not susceptible to cefotaxime
• 23 of these isolates were fully resistant (MIC
  4 µg/mL)
• 17 were not susceptible to cefepime
• 10 of these isolates were fully resistant (MIC
  4 µg/mL)

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• Imipenem, meropenem, and teicoplanin had good in
  vitro activity against these isolates
• Only 7 were susceptible to azithromycin,
• and 57 of the isolates had an MIC of
  azithromycin of 128 µg/mL.
• 54 of the isolates that were not susceptible to
  azithromycin (MIC 1 µg/mL) were also resistant
  to clindamycin (MIC 1 µg/mL)

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• According to the MIC90 values, fluoroquinolones
  demonstrated potent activity against nearly all
  of the NVS isolates tested
• (relative MIC90 values sitafloxacin
  garenoxacin moxifloxacin gatifloxacin
  ciprofloxacin levofloxacin)

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• Nutrition limitation within vegetation, slow
  growth rate, and production of exopolysaccharide
  contributed to a longer course of endocarditis
  and required a longer duration of effective
  antibacterial coverage

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• The existence of significant resistance to
  ß-lactams and macrolides among these NVS isolates
  emphasizes the need for accurate identification
  and antimicrobial susceptibility testing of these
  organisms