Microbiology, parasitology & COVID-19

Gram positive bacteria

Staph coagulase negative

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Joshua A. Lieberman, M.D, Ph.D.

Last author update: 1 April 2018
Last staff update: 4 May 2023

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PubMed Search: Staphylococcus sp[TIAB] coagulase negative

Joshua A. Lieberman, M.D, Ph.D.
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Cite this page: Lieberman, J.A. Staph coagulase negative. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/microbiologystaphylococcus.html. Accessed June 9th, 2023.
Definition / general
  • Gram stain: positive
  • Morphology: cocci in clusters
  • Facultative anaerobe
  • Part of normal flora of the skin and mucus membranes
Essential features
  • Unlike S. aureus, coagulase test is negative
  • Greek for staphyle ("bunch of grapes") and kokkos ("berry") (Emerg Infect Dis 2013;19:1553)
  • Coagulase negative staphylococci (CoNS)
  • Many recognized species
  • Important species include Staphylococcus epidermidis, S. saprophyticus, S. lugdunensis and S. haemolyticus
  • Common contaminants; to distinguish from true infection rely on clinical judgment, patient features (e.g. hematologic malignancy / immunosuppression) and number / site (central venous catheter vs. venipuncture) of positive cultures (Eur J Clin Microbiol Infect Dis 2012;31:2639, Clin Infect Dis 2004;39:333)
  • Biofilm formation and adherence to indwelling devices, catheters
  • Culture conditions
    • Blood agar plates (nonselective)
    • Enrichment broth (tryptic soy broth) in parallel increases culture yield / organism recovery
    • Chromogenic agars
    • Temperature: 34 - 37 °C, with most species producing growth within 24 hours; a few CoNS, such as S. lentus, may require up to 36 hours for colonies to appear
  • Gram positive
  • Catalase positive
  • Coagulase negative
  • Readily identified by matrix associated laser desorption ionization - time of flight mass spectrometry (MALDI-TOF MS)
    • MALDI-TOF MS is an increasingly essential tool in the clinical microbiology laboratory for rapid detection of microorganisms
  • Small colony variants (SCV) (Clin Microbiol Rev 2016;29:401)
    • Especially S. epidermidis, S. capitis and S. warneri
    • SCVs more often in foreign body associated infections, chronic or relapsing infections
    • Represent metabolic changes, adaptation to intracellular growth
  • Ferment fructose
  • S. saprophyticus resistant to novobiocin
  • Beta lactamase resistance and methicillin resistance are widespread
    • Vancomycin for methicillin resistant
    • Nafcillin for methicillin susceptible
    • Presence of mecA and altered PBP2a (penicillin binding protein)
  • High rates of resistance to fluoroquinolones, clindamycin, aminoglycoside and macrolides in hospital associated strains; linezolid resistance rare (Antimicrob Agents Chemother 2014;58:1404)
Clinical images

Contributed by Joshua A. Lieberman, M.D., Ph.D.

Chocolate agar

Gross description
  • Colonies typically small, beige to white
  • Variable hemolysis, depending upon species
Microscopic (histologic) description
  • Gram positive cocci in clusters, similar to other staphylococci
Microscopic (histologic) images

Contributed by Joshua A. Lieberman, M.D., Ph.D.

Gram stain

Molecular / cytogenetics description
  • Commercial polymerase chain reaction (PCR) based methods, including mecA detection (J Clin Microbiol 2013;51:2072)
  • Broad range 16S PCR followed by sequencing and bioinformatic identification
Differential diagnosis
  • Primarily other staphylococci
  • Aerococcus
  • Micrococcus
    Board review style question #1
    Most concerning mechanism of antibiotic resistance in the organism shown in the Gram stain below is:
    1. Altered penicillin binding protein
    2. Extended spectrum beta lactamase production
    3. Mutation in DNA gyrase
    4. Point mutation in the ribosomal 23S rRNA gene
    5. Porin mutation
    Board review style answer #1
    A. Altered penicillin binding protein. The image shows Gram positive cocci in clusters. PBP2a, an altered (low affinity) penicillin binding protein, is the product of the mecA gene, and mediates oxacillin / methicillin resistance in staphylococci. Answer B is incorrect because although many Staphyloccoci strains are resistant to a variety of beta-lactam antibiotics, the extended spectrum beta lactamases (ESBLs) are a specific class of enzymes that destroy a wide range of beta-lactam antibiotics, and these are found in Gram-negative pathogens, particularly Enterobacteriaceae. Answer C is incorrect because mutations in DNA gyrase confer resistance to quinolone / fluoroquinolone antibiotics. Answer D is incorrect because point mutations in the 23S rRNA gene confer macrolide resistance, especially in Helicobacter pylori, by altering drug binding sites. Answer E is incorrect because porins are outer membrane proteins only found in Gram negative organisms. Porin mutations can block or reduce drug influx and drug effect; examples include Acinetobacter baumanii and imipenem and Pseudomonas aeruginosa and tobramycin.

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