It’s pass-level to know that Neisseria are gram-negative diplococci. Don’t confuse with Strep pneumo, which is gram-positive diplococci.
Neisseria meningitidis
The answer on USMLE for cause of meningitis in three groups:
1) College-age students living in close quarters or military barracks;
2) Child or older who has non-blanching rash (means doesn’t turn white when pressure applied); can be described as purpuric or ecchymotic;
3) Patient with terminal complement deficiency, where there is Hx of recurrent gonoccocal or meningococcal disease in family member or patient. Terminal complement deficiency (C5-9), aka “total hemolytic complement deficiency” (seen NBME write it like this), causes recurrent Neisserial infections.
Waterhouse-Friderichsen syndrome is bilateral hemorrhagic necrosis of the adrenal cortices secondary to meningococcal septicemia. This can present with or without meningitis. The USMLE might show you a picture of a purpuric rash on a child + low BP.
The key point about WFS is that cortisol is low. Cortisol normally helps maintain basal BP by upregulating alpha-1 receptors on peripheral arterioles. This allows norepinephrine and epinephrine to bind (i.e., “cortisol is permissive of the effects of catecholamines”) and constrict arterioles. In the setting of WFS, giving saline + vasopressors (such as norepinephrine) won’t work, since the underlying glucocorticoid (cortisol) isn’t there. So the USMLE wants hydrocortisone as the pharmacologic treatment after normal saline.
N. meningitidis is encapsulated. This means there is increased risk of infection in those with asplenia / sickle cell. 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.
Neisseria gonorrhoeae
Causes STI with mucopurulent discharge; this may progress to pelvic inflammatory disease (PID) in females, with increased risk of ectopic pregnancy due to scarring of Fallopian tubes.
There will be gram-negative diplococci on light microscopy. In contrast, Chlamydia will not show any organisms on LM. So if we see the gram-negative diplococci, we always co-treat for Chlamydia.
In other words, if the gram-(-) diplococci are seen under LM, there’s no way to know if Chlamydia is also there or not since the latter shows no organisms, so if a patient has Gonorrhea, the proper Tx is IM ceftriaxone (for gonococcus), PLUS either oral azithromycin or doxycycline (for Chlamydia).
If patient develops PID despite having been treated early with ceftriaxone for Gonorrhea, the answer for why this happened can be “Hx of improper antibiotic treatment,” where the patient was supposed to be co-treated for Chlamydia with azithromycin or doxy but was only given the ceftriaxone for Gonorrhea.
If patient presents with PID who’s septic (i.e., high fever, tachy, high WBCs), USMLE wants “admit to hospital + IV antibiotics,” not the outpatient combo of IM + oral antibiotics.
2CK form assesses that if an asymptomatic patient comes in after a partner tested positive for Gonorrhea or Chlamydia, the answer is give treatment without waiting for test results.
Gonorrhea doesn’t cause reactive arthritis; it causes gonococcal arthritis, which will present one of two ways on NBME: 1) monoarthritis of the knee; or 2) triad of mono- or polyarthritis + cutaneous papules/pustules + tenosynovitis (inflammation of tendon sheaths; stems like to give deQuervain tenosynovitis).
Reactive arthritis (usually caused by Chlamydia), in contrast, presents as triad of urethritis, polyarthritis, and conjunctivitis. Rarely it can be caused by GI infections. But the point is that reactive arthritis is not caused by Gonococcus. The latter causes gonococcal arthritis, which presents as per above.
Treat gonococcal arthritis same as urethritis –> ceftriaxone + azithro or doxy, since the patient may also carry Chlamydia.
Gonococcus is notoriously difficult to culture in patients who have arthritis but no overt urethritis. That is, the patient may have a negative arthrocentesis and throat/urethral swabs. So the diagnosis of arthritis is often made clinically. If the Q mentions papules/pustules on the skin, this makes it hyper-obvious for Gonorrhea. I mention this because occasionally an NBME Q will say the arthrocentesis is negative, and this somehow confuses students. But arthrocentesis is not very sensitive for organisms in the setting of septic arthritis. This can apply to S. aureus as well (I’ve seen this on NBME), but false-negative results for gonococcus are notably common, so don’t be thrown off by that.
Can cause ophthalmia neonatorum (fancy way of saying neonatal conjunctivitis).
Gonococcal conjunctivitis will present in the first week of life with yellow discharge from the eye(s). Chlamydia tends to present after the first week.
The USMLE vignette will be vague, where the student says, “But how are we supposed to know it’s not Chlamydia, just because it’s first week of life, that’s it?” And my response is: if they give you Chlamydia ophthalmia neonatorum, they’ll always tie it to subsequent pneumonia somehow, since that is such a HY point. You need to be aware that Chlamydia drains through the nasolacrimal duct down into the lungs, so if they give you a 3-week old with pneumonia following conjunctivitis, you know that’s Chlamydia.
Prophylaxis for gonococcal conjunctivitis is erythromycin ointment; treatment in the neonate is IM 3rd-gen cephalosporin (usually cefotaxime in peds).
Prophylaxis for chlamydial conjunctivitis is treatment of the mother while pregnant; treatment in the neonate is oral erythromycin.
Same as with N. meningitidis, patients have increased risk of infection with terminal complement (C5-9) deficiency. Sometimes the vignette can give a patient with recurrent N. gonorrhoeae or N. meningitidis + ask what is likely deficient, and the answer can simply be “C7” or “C8.” Seems weird/out of place, but it’s easy if you know terminal complement deficiency is exceedingly HY for Neisserial infections.
A vaccine cannot be made against N. gonorrhoeae because it has pilus proteins on its cell surface that undergo antigenic variation. This is in contrast to N. meningitidis, where we make a vaccine against the polysaccharide capsule. N. gonorrhoeae, however, does not have a capsule.
Haemophilus influenzae
You need to be aware of H. influenzae type B as well as non-typeable.
H. influenzae type B (HIB) causes epiglottitis and meningitis.
H. influenzae non-typeable is a less common cause of otitis media (compared to S. pneumo) and can also cause pneumonia in COPD. I’ve never seen it assessed on NBME as the answer for otitis media, but I’m letting you know that occasionally you might read about H. influenzae being a cause of otitis media after S. pneumo. But this refers to H. influenzae non-typeable, not type B. I’ve seen one Q only on NBME of H. influenzae non-typeable pneumonia in a COPD patient.
HIB has a polysaccharide capsule. The vaccine is a conjugate vaccine, where a protein is attached to the polysaccharide capsule so that it can be expressed on MHC-II. USMLE wants you to know that T-independent antigens are non-proteinaceous (i.e., polysaccharide capsules, LPS of gram-negatives, etc.) and therefore cannot be expressed on MHC-II molecules. Therefore, by attaching a protein to it (e.g., flagellin), it can be expressed on MHC-II and presented to CD4+ T cells for a more robust immune response. This vaccine point is HY for immuno for USMLE.
Epiglottitis is seen in unvaccinated and immigrants (can be unvaccinated), as well as patients with asplenia or sickle cell (auto-splenectomy).
X-ray of neck shows “thumbprint sign.”
Presents as child who has fever + difficulty breathing. They can say the kid is drooling and/or in tripod positioning (facilitates use of accessory muscles).
USMLE wants intubation as immediate answer. Epiglottitis is a medical emergency that can lead to sudden occlusion of the airway.
Antibiotic Tx following intubation = 3rd-gen cephalosporin (cefotaxime in peds, or ceftriaxone); give rifampin to close contacts.
Legionella
Classically acquired via aerosols from air conditioners. The question can simply say “residential facility” or “business trip” to imply exposure to large AC units. If the Q gives Legionella pneumonia + they ask about acquisition, the answer can be “environmental aerosols.”
Cause of atypical pneumonia (interstitial pneumonia), with bilateral interstitial infiltrates. “Legionnaire’s disease” refers to severe pneumonia/illness due to Legionella.
Can also cause hyponatremia and diarrhea.
Diagnosed with urine antigen test.
Treat with azithromycin or doxycycline.
Mycoplasma
Most common bacterial cause of atypical pneumonia (interstitial pneumonia). Viruses are technically most common, but for USMLE, if a patient has a bilateral pneumonia with interstitial infiltrates, Mycoplasma is the likely cause.
Referred to as “walking pneumonia,” which refers to a young, healthy adult who’s literally been walking around but who has a dry cough + low-grade fever, where the CXR shows bilateral infiltrates. There is an NBME Q that literally trolls the concept of walking pneumonia, where they say a 23-year-old male was hiking for 8 hours the day before + has a pneumonia, and the answer is Mycoplasma.
In general, you need to be aware that lobar pneumonia is usually S. pneumo, and bilateral pneumonia is usually Mycoplasma (in AIDS patients, bilateral pneumonia is Pneumocystis).
There is one NBME Q that gives right lower lobe interstitial infiltrates, with Mycoplasma as the correct answer, where S. pneumo isn’t listed. This means the word “interstitial” wins over location.
Can cause cold agglutinins (IgM antibodies against RBCs), leading to hemolysis. In other words, bilateral pneumonia + low Hb = Mycoplasma. High LDH can also sometimes be seen. RBCs are packed with LDH, so high LDH on USMLE is often their way of saying hemolysis.
Treat with azithromycin or doxycycline.
HY for Step 1 NBMEs: they will ask why beta-lactams such as amoxicillin are ineffective against Mycoplasma. The answer is because it lacks a peptidoglycan cell wall.
Chlamydia
Obligate intracellular.
Chlamydia pneumoniae (not Chlamydia trachomatis) is technically another cause of interstitial/atypical pneumonia after Mycoplasma and Legionella, but I’ve never seen this assessed on NBME.
Chlamydia psittaci is a cause of atypical pneumonia in bird owners or those who work at a pet store with birds.
Treat with azithromycin or doxycycline.
Chlamydia trachomatis D-K (the actual STI) can cause pneumonia in neonates following conjunctivitis. This is HY. The Q will give a 3-week-old who had conjunctivitis 1-2 weeks earlier, who now has low-grade fever + bilateral wheezes. The labs can show a high % of lymphocytes, since Chlamydia lives intracellularly so requires cell-mediated immunity to clear it. In contrast, other organisms, like S. pneumo, which live outside the cell, cause a neutrophilic shift instead, since neutrophils are used for humoral immunity.
Prophylaxis for Chlamydia neonatal conjunctivitis is treating the mom while pregnant. Treatment in the neonate is oral erythromycin. Topical is wrong because it will not kill what has already entered the nasolacrimal duct. Topical erythromycin is used as prophylaxis for gonococcal conjunctivitis; Tx for the latter is cefotaxime.
Bordetella pertussis
Classic whooping cough presents as succession of many coughs followed by an inspiratory stridor.
What you need to know for USMLE is that this can absolutely present in an adult and that they can be vague about it, just describing it as a regular cough. There is an NBME Q where they give pertussis in a 19-year-old, and I see students confused thinking it must be a kid. This is not the case. Write a letter to NBME if you disagree.
The way you’ll know it’s pertussis, however, is they will say there’s hypoglycemia and/or post-tussive emesis, which means vomiting after coughing episodes.
Pertussis can cause super-high WBC counts in the 30-50,000-range, where there are >80% lymphocytes. This is called reactive lymphocytosis. This makes it resemble ALL. So you should know for Peds that ALL-like laboratory findings + cough = pertussis.
Q will ask number-one way to prevent –> answer = vaccination (not hard, but they ask it). Pertussis is part of TDaP. The pertussis component is killed-acellular; the tetanus and diphtheria are toxoid.
Erythromycin can be given to patients with active cough; USMLE doesn’t give a fuck about pertussis stages.
Close contacts should also receive erythromycin.
Francisella tularensis
Cause of atypical pneumonia in patients with exposure to rabbits.
Can sometimes cause ulcerated skin lesions.
Infection is called tularemia.
Rickettsia
Refers to a genus of bacteria that are obligate intracellular (same as Chlamydia, which is also obligate intracellular).
Rickettsia rickettsii causes Rocky Mountain spotted fever (RMSF), which is a palms and soles rash (sometimes the Q can say wrists/ankles instead of palms/soles) that migrates toward the trunk (centripetal rash).
RMSF is considered a form of vasculitis and is spread by dermacentor wood tick. It is treated with doxycycline.
“Typhus” refers to rash + fever+ headache conditions caused by rickettsia.
Rickettsia prowazekii causes epidemic typhus; spread by louse.
Rickettsia typhi causes endemic typhus; spread by fleas.
Rickettsia tsutsugamushii causes scrub typhus; spread by mites.
Rickettsia cause a positive Weil-Felix test, which means there are positive titers to Proteus-O antigen. Sounds weird, but I don’t know what to tell you.
Coxiella burnetii
Causes Q-fever, an atypical pneumonia in those with exposure to farm animals, especially cattle.
Was once considered a type of Rickettsia, but has now been recategorized into its own genus. It is Weil-Felix negative.
Brucella
Acquired from unpasteurized goat products (i.e., cheese, milk).
Brucellosis causes undulating fever, which presents as afternoon fevers and normal body temperature in the morning.
Invasion to the CNS is called neurobrucellosis, which can present as meningoencephalitis.
Pasteurella multocida
Can cause skin infection following a cat or dog bite.
Bartonella henselae
Can cause skin infection following cat or dog scratch (hence cat-scratch disease).
Causes non-caseating granulomatous inflammation seen on silver stain.
The Q need not say the patient has a pet. NBME might say there is an 8-year-old girl with a papule on the finger, where biopsy shows granulomatous inflammation on silver stain, and the answer is simply Bartonella henselae.
Treat with azithromycin.
Can cause bacillary angiomatosis in immunocompromised patients, which is proliferating blood vessels presenting as raised, red/violaceous skin lesions. The condition is known to resemble Kaposi sarcoma.
