You can see that catalase (+) vs (-) is how we differentiate the Staph vs Strep.
Staph aureus
Gram (+) cocci in clusters; catalase (+); coagulase (+).
Grows yellow on culture medium (“golden staph”).
Produces Protein A, which can cleave the Fc region of IgG.
Humans can carry S. aureus within the nares (nostrils). If USMLE asks about nosocomial transmission, the answer is “carried within the nares of hospital staff.”
Highest yield points for USMLE is that it causes:
- Acute endocarditis (no previous valve abnormality); usual organism for IV drug users.
- Skin infections (cellulitis, erysipelas, impetigo, abscesses). S. aureus eclipses Group A Strep (Strep pyogenes) for cellulitis, as well as for both bullous and non-bullous impetigo. Group A Strep eclipses S. aureus for erysipelas.
- Mastitis in breastfeeding women.
- Osteomyelitis; most cases are S. aureus. In sickle cell, however, there is increased risk of Salmonella osteomyelitis.
- Septic arthritis; most cases are S. aureus. If vignette explicitly talks about promiscuity or gives cutaneous papules/pustules, the answer is Gonorrhea instead.
- Toxic shock syndrome; TSST toxin is a super-antigen that bridges MHC-II on macrophages with T-cell receptor on CD4+ T cells. Once the bridging has occurred, macrophages release cytokines. TNF-α causes hypotension; IL-1 causes fever. Do not confuse this mechanism with endotoxic shock, which is when the lipid A component of lipopolysaccharide (LPS) from gram-negative bacteria binds to CD14 (Toll-like receptor) on macrophages; the macrophages then release cytokines.
- Staphylococcal scalded skin syndrome (SSSS); exfoliative toxin causes a generalized salmon-pink rash and desquamation of palms and soles in neonates.
- Food poisoning due to heat-stable pre-formed toxin in meats or dairy products (i.e., creams, potato salad) that have been sitting at room temperature for a while. Presents as vomiting 1-6 hours after consumption (diarrhea is +/-).
- Pneumonia following influenza infection.
- Bacterial superinfection on scabies lesions.
- Common organism in many immunodeficiency Qs, including leukocyte adhesion deficiency and chronic granulomatous disease (NADPH oxidase deficiency).
HY points about treating S. aureus:
90% of community Staph (i.e., methicillin-sensitive S. aureus; MSSA) produces beta-lactamase. This means penicillin, amoxicillin, or ampicillin alone will usually not work and are wrong treatments. Oral amoxicillin combined with clavulanate (Augmentin), or IV ampicillin combined with sulbactam, serve the purpose of covering S. aureus, since clavulanate and sulbactam are beta-lactamase inhibitors, but giving amoxicillin or ampicillin alone should be considered inadequate for covering Staph.
What this means is, when we treat S. aureus, we want to give a methicillin-class beta-lactam, since these are heavily steric and are beta-lactamase resistant. Methicillin isn’t given clinically because it causes interstitial nephritis (eosinophils in the urine + rash), but oral dicloxicillin (not doxycyline) and IV flucloxacillin are frequently given, since these cover Staph.
So for skin, we can give oral dicloxacillin or cephalexin out-patient, or IV flucloxacillin or cephazolin in-patient, as these will cover S. aureus in addition to Group A Strep.
First-generation cephalosporins, such as cephalexin and cephazolin, are also beta-lactamase resistant and are the same as the methicillin-class beta-lactams for all intents and purposes.
For impetigo only, USMLE likes topical mupirocin, but for oral meds, use as per above.
The only other methicillin-class beta-lactam you need to know for USMLE is nafcillin, which is hard-hitting and used for confirmed MSSA endocarditis. It is also known to cause interstitial nephritis.
I’ve seen this on NBME. Other agents like cloxacillin, oxacillin, etc., I’ve never seen show up on NBME, but students get fanatical about listing off different drugs.
For USMLE, they might ask you why Staph is resistant to amoxicillin but not to cephalexin; the answer is “production of penicillinase,” or “production of beta-lactamase,” as we said.
If they ask how MSSA → MRSA, the answer is “altered penicillin-binding protein.” We know “production of beta-lactamase” is wrong here because MSSA already produces beta-lactamase, so clearly that mechanism can’t be the reason why it can become MRSA.
MRSA endocarditis is treated with vancomycin. Vancomycin, however, has poor skin penetration, so if a cutaneous infection is caused by MRSA, we treat that with clindamycin, doxycycline, or trimethoprim-sulfamethoxazole. You do not need to memorize these latter three treatments and USMLE won’t ask. I’m just saying as a medicine 301-level tangential point that vancomycin isn’t used for MRSA skin infections. But it’s pass-level you know that MRSA endocarditis is treated with vancomycin.
Empiric Tx for endocarditis is vancomycin (covers gram-positives, including MRSA) and gentamicin (covers gram-negatives). There are other regimens, but you should know that one. Do blood cultures before antibiotics (asked on 2CK NBME).
Staph epidermidis
Normal skin flora.
Can cause infections of prostheses, including heart valves and joint replacements.
Vancomycin + gentamicin is the normal empiric Tx for endocarditis. If the patient has prosthetic material in the heart, add rifampin.
Staph saprophyticus
Can cause UTIs leading to staghorn calculi (aka struvite, or ammonium magnesium phosphate stones), which resemble rams horns.
This is because it is urease (+), and struvite stones form at high pH.
Points about hemolysis types:
Group A and B Strep both refer to β-hemolytic Strep (i.e., Group A and B Streps do not equal α- vs β-hemolytic, respectively).
β-hemolysis means complete hemolysis (clear zone of hemolysis on blood agar).
α-hemolysis means partial hemolysis (green zone of hemolysis on blood agar).
γ-hemolysis means no hemolysis (no change on blood agar).
Strep pyogenes (Group A Strep)
Gram-positive cocci in chains.
Infections cause elevation of anti-streptolysin titers.
Causes Strep pharyngitis, scarlet fever (strawberry tongue + salmon pink body rash [due to erythrogenic toxin]), and skin infections (cellulitis, erysipelas, impetigo).
Post-streptococcal glomerulonephritis (PSGN) is a type-III hypersensitivity (immune complex deposition) that can occur following both pharyngitis as well as cutaneous infections (i.e., it is not just caused by pharyngitis). It presents as red urine (hematuria) 1-3 weeks following the infection. This is not to be confused with IgA nephropathy, which is red urine 1-3 days (not weeks) following a viral infection. In PSGN, serum complement protein C3 will be decreased.
Rheumatic heart disease is a type-II hypersensitivity that only occurs following pharyngitis. The immune system makes antibodies against the M-protein of S. pyogenes that cross-reacts (molecular mimicry) with the mitral valve (on USMLE, RHD will be mitral 29/30 times). Penicillin must be given to treat Strep pharyngitis to prevent rheumatic heart disease. However, penicillin will not prevent PSGN. In RHD, the patient will have mitral regurg acutely, followed by mitral stenosis years later after the valve scars over. 99% of mitral stenoses are due to history of RHD.
Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococci (PANDAS) is a psych condition asked on USMLE, where a child can develop a tic, ADHD, or OCD following a Strep pyogenes infection.
S. pyogenes can cause toxic shock-like syndrome due to exotoxin A production, where the vignette can give cellulitis + shock, and the answer is just “MHC-II and TCR” as the immunologic receptors bound. In other words, TSST toxin of S. aureus, as well as exotoxin A of S. pyogenes, both can cause shock via the same mechanism.
Strep agalactiae (Group B Strep)
Gram-positive cocci in chains.
Causes neonatal meningitis, pneumonia, and sepsis.
Rectovaginal swabs performed in pregnant women at 36 weeks’ gestation to determine whether intrapartum IV penicillin or ampicillin prophylaxis is given.
For 2CK/3, indications for GBS prophylaxis:
- Positive swab at 36 weeks’ gestation.
- GBS bacteriuria at any point in the current pregnancy, even if successfully treated.
- Hx of prior pregnancy where there was early-onset GBS disease in the neonate (i.e., meningitis, pneumonia, or sepsis). Mere colonization (i.e., mere positive test) in a prior pregnancy is not an indication for giving prophylaxis in current pregnancy.
- If the mother’s GBS status is unknown at parturition, give prophylaxis if any one of the following met: 1) maternal fever >38C; 2) rupture of membranes >18 hours; 3) premature delivery (<37 weeks).
Neonatal infections on USMLE will be caused by GBS, Listeria, or E. coli. If they say a neonate has an infection caused by gram-positive cocci, the answer is GBS; if they say gram-positive rods, that’s Listeria; if they say gram-negative rods, that’s E. coli.
Enterococcus
Gram-positive cocci in chains.
Normal flora within the gastrointestinal and urinary tracts.
The answer on USMLE for endocarditis following genitourinary manipulation (e.g., catheterization or TURP for BPH).
Treated with ampicillin. If resistant to ampicillin, we treat with vancomycin. If resistant to vancomycin (VRE; vancomycin-resistant enterococci), drugs such as linezolid or daptomycin can be used. USMLE will not assess the latter two treatments for VRE. The important point is that you are merely aware VRE is an important nosocomial pathogen, same as MRSA.
Strep gallolyticus / Strep infantarius
Formerly known as Strep bovis, but USMLE is old school, so it is not a guarantee the nomenclature has changed on the exam.
Can cause endocarditis in the setting of colon cancer.
Strep pneumoniae
Gram-positive diplococci (don’t confuse with Neisseria gonorrhea and meningitidis, which are gram-negative diplococci).
Most common cause of lobar pneumonia and otitis media.
Can also cause meningitis and sinusitis.
Ultra-HY as cause of sepsis in asplenia and sickle cell (auto-splenectomy).
USMLE might give chest infection in a teenager or young adult, where they say there’s right lower lobe dullness to percussion. You know that’s S. pneumo. If they give bilateral interstitial infiltrates, that is most likely Mycoplasma. Pneumonia discussion is lengthy.
You don’t want to memorize S. pneumo as the “most common” organism for meningitis because USMLE wants you to differentiate it from Neisseria meningitidis (meningococcus). If they give college dormitories, military barracks, or close quarters, this suggests N. meningitidis over S. pneumo. In addition, N. meningiditis causes non-blanching rash (i.e., does not turn white when pressed); this can refer to purpura or ecchymoses. If they mention a rash, the answer is meningococcus, not S. pneumo. Meningococcus also can cause Waterhouse-Friderichsen syndrome (bilateral hemorrhagic necrosis of the adrenal cortices, leading to hypotension non-responsive to norepinephrine).
Empiric Tx for community-acquired pneumonia (CAP) is azithromycin on USMLE.
USMLE doesn’t assess levofloxacin (respiratory fluoroquinolone) for pneumonia Tx, but you could be aware that patients who’ve had antibiotics in the past 3 months, or who have significant comorbidities, sometimes they are upgraded to a respiratory fluoroquinolone. But offline NBME 8 for 2CK has azithromycin straight-up as the answer.
For CAP where the patient is septic, ceftriaxone +/- vancomycin is given. Ceftriaxone is powerful and effective against S. pneumo. Some strains are developing resistance, so vancomycin can be added (asked on one 2CK Q).
Meningitis empiric Tx is ceftriaxone + vancomycin. In elderly, ampicillin can be added.
Empiric Tx for otitis media is penicillin or amoxicillin. Recurrent otitis media, however, we can add clavulanate (Augmentin). But initially, we just give amoxicillin or penicillin alone for otitis media.
Empiric Tx for sinusitis is amoxicillin/clavulanate (Augmentin). This is because sinusitis can be caused by other organisms as well, including S. aureus, so we need expanded coverage straight-up.
Patients with asplenia / sickle cell have increased risk of infections due to encapsulated organisms. This namely refers to S. pneumo, H. influenzae type B, and N. meningitidis, which all have polysaccharide capsules. This is because encapsulated organisms require opsonization (with C3b or IgG) and phagocytosis for clearance, and the spleen is where we have 50% of the immune system’s reservoir of macrophages. So if we lose the spleen, we lose substantial phagocytic capacity. Patients must receive additional rounds of vaccination against these three organisms.
If USMLE asks which organism we are most worried about when we give penicillin prophylaxis to sickle cell patients (or any asplenia patient for that matter), the answer is S. pneumo. Choose this answer over H. influenzae type B and N. meningitidis, even though, yes, the latter two are clearly important to cover as well.
For 2CK, we vaccinate against S. pneumo by giving PCV20 alone, OR by giving PCV15 + PPSV23 months later. I talk about this stuff in detail in my HY Pulmonary PDF.
Strep viridans (Strep mitis, mutans, sanguinis)
Cause subacute endocarditis (i.e., patient has previous valve abnormality, such as from history of rheumatic heart disease, or bicuspid aortic valve), classically following a dental procedure; can create limit-dextrins, which are carbohydrate structures that can adhere to heart valves.
