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HY points about each drug followed by a quiz at the end
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You do not need to know every cephalosporin for the USMLE. The following are the highest yield ones and their respective generations.
As the generation # ascends, so does the general breadth of the organism coverage.
1st gen: cephalexin, cefazolin
Cephalexin is oral. Cefazolin is IV. Therefore, cefazolin is the inpatient form of cephalexin.
When do we use these agents?
1st generation cephalosporins notably cover community Staph (i.e., methicillin-sensitive S. aureus; MSSA) –> cellulitis; erysipelas; severe impetigo (mild impetigo we use topical mupirocin).
For cellulitis and impetigo (bullous and non-bullous), S. aureus exceeds Strep pyogenes (Group A Strep). For erysipelas, Group A strep exceeds S. aureus.
Therefore, we need Staph coverage when dealing with skin infections.
Since 90% of MSSA produces beta-lactamase, which means penicillin, amoxicillin, and ampicillin are not effective treatments against Staph.
So if we choose to use a beta-lactam for Staph, we need to use beta-lactamase-resistant beta-lactams, such as dicloxicillin (oral; outpatient) or flucloxcillin (IV; inpatient). Nafcillin is classic for confirmed MSSA endocarditis. Oxacillin is used for osteomyelitis and septic arthritis.
The first-generation cephalosporins are essentially the equivalent of the beta-lactamase-resistant beta-lactams.
In other words, if you want to treat anything that could potentially have MSSA as the culprit (namely skin), you can give oral cephalexin as a satisfactory treatment. Otherwise, just give oral dicloxacillin (do not confuse this with doxycyline).
If the patient’s skin presentation is severe, you can give IV cefazolin. Otherwise, give IV flucloxacillin.
Bottom line: when you hear cephalexin or cefazolin, the first thing that should go through your mind is: “those are for community Staph coverage; can be used for skin or bone stuff.”
“What about if a patient as a beta-lactam allergy? How does that relate to cephalosporins?” What you need to know for USMLE:
- If patient has Hx of rash to beta-lactams (e.g., penicillin), yes, it’s okay to give a cephalosporin. The crossover for allergy is low (<10%).
- If the patient has Hx of anaphylaxis to beta-lactams, no, do not give a cephalosporin. Use another agent instead depending on the condition. For skin, agents such as clindamycin, doxycycline, TMP/SMX, and linezolid are frequently used. These agents are otherwise usually reserved for MRSA of skin (vancomycin as poor skin penetration).
2nd gen: cefoxitin
Only real thing you need to know is that cefoxitin is frequently used as a prophylactic antibiotic prior to surgery, especially in pediatrics.
3rd gen: ceftriaxone, cefotaxime, ceftazidime
These agents are harder hitting and have broader coverage than the previous two generations.
When is ceftriaxone the answer? (Literally. All are HY).
- Meningitis:
- Empiric Tx for bacterial meningitis is ceftriaxone + vancomycin.
- Confirmed meningococcal meningitis can be managed with ceftriaxone alone (vancomycin is removed because it’s only needed for gram-positives).
- Rifampin, not ceftriaxone, is given to close contacts of patients with meningococcal meningitis.
- Gonorrhea:
- Urethritis and the Dx is uncertain: always co-treat for both chlamydia and gonorrhea with azithromycin (or doxycycline) for the chlamydia + ceftriaxone for the gonorrhea.
- Urethritis with confirmed gonococcus: co-treat as per above.
- Urethritis where “nothing grows,” but vignette says nothing about gonococcus: co-treat.
- Urethritis where “nothing grows” and vignette explicitly says gonococcal testing was negative: azithro or doxy only.
- Gonococcal arthritis presents one of two ways on USMLE:
- 1) monoarthritis of large joint (such as the knee) in sexually active young-ish patient;
- 2) triad of polyarthritis, tenosynovitis, and cutaneous papules in young-ish patient;
- Treatment is ceftriaxone (+ azithro or doxy for potential asymptomatic chlamydia as well).
- Sickle cell patients with sepsis or bone infection:
- Ceftriaxone has gram-negative coverage and can therefore cover Salmonella in sickle cell patients.
- Patients with severe Strep pnuemo infections:
- Ceftriaxone is notably effective against Strep pneumo.
- New 2CK NBME Q adds vancomycin to ceftriaxone for community-acquired Strep pneumonia (because of increasing resistance of Strep pneumo to ceftriaxone, adding vancomycin, even when the infection isn’t nosocomial, is considered acceptable; this is on the NBME so it’s not even my opinion).
- Spontaneous bacterial peritonitis:
- Three vignette types here: 1) patient with cirrhosis; 2) patient who recently underwent peritoneal dialysis; 3) patient with nephrotic syndrome.
- Patient will have fever + diffuse abdominal pain + a fluid wave; antibiotic treatment? –> answer = ceftriaxone.
- Patients with sepsis (2CK level):
- Sepsis = SIRS + source of infection.
- SIRS = systemic inflammatory response syndrome = 2 or more of the following 4 variables:
- Temperature <36C or >38C;
- HR >90;
- RR >20;
- WBCs <4,000 or >12,000.
- So for instance, patient has pneumonia + sepsis; Tx? –> ceftriaxone common answer (not only covers S. pneumo well but patient is also septic).
- Prostatitis + pyelonephritis are classically treated with ciprofloxacin (a fluoroquinolone), however if the patient is septic, then ceftriaxone can be the answer (cipro is still correct, even in sepsis, but the Q won’t list both).
- I.e., 38F + CVA tenderness + fever 38.5C + HR 100; answer = ceftriaxone; student says, “Wait, I thought ciprofloxacin was how we treat pyelo.” –> Yeah, it is. But the patient’s septic, which is why ceftriaxone is correct here.
- Broad-spectrum antibiotic coverage for nosocomial infections:
- Patient with hospital-/ventilator-acquired pneumonia or other type of nosocomial infection will receive broad-spectrum antibiotic coverage. Ceftriaxone is a classic agent used in combination with vancomycin.
When is cefotaxime the answer?
- Really HY to know that we do not give ceftriaxone to children < age 6 if we can help it (increases displacement of bilirubin from albumin and can cause jaundice). Age 6 or greater, yes, ceftriaxone is okay.
- Cefotaxmine therefore is the ceftriaxone equivalent in peds. USMLE assesses the age:
- 12-month-old girl with sickle cell + missed dose of penicillin prophylaxis + septic; Tx? –> answer = cefotaxime; wrong answer is ceftriaxone (on one of the 2CK IM forms, where both are listed).
- 6-year-old girl + sepsis; Tx? –> answer = ceftriaxone (cefotaxime not listed; on newer 2CK NBME).
When is ceftazidime the answer?
- Covers Pseudomonas (HY). Iow, in your mind, ceftazidime should = Pseudomonas coverage.
- Can be combined with vanc for nosocomial infections or general broad-spectrum coverage.
4th gen: cefepime
When is cefepime the answer?
- Hard-hitting agent that covers Pseudomonas. That is: both ceftazidime (3rd gen) and cefepime (4th gen) cover Pseudomonas.
- Combined with vanc for broad-spectrum nosocomial coverage. Q on one of the 2CK forms gives nosocomial infection, then says, “cefepime is commenced; which other agent should be added?” Answer = vancomycin. Easy because they asked for vanc rather than cefepime, but the point is that this combo is HY for broad-spectrum nosocomial coverage.
5th gen: ceftaroline, ceftobiprole
When would ceftaroline or ceftobiprole be the answers? –> newer 5th gen cephalosporins that cover MRSA.
- Have never seen these asked on any NBME material, but they’re important to mention because they cover MRSA and complete the discussion of the cephalosporin generations.
- Iow, when you hear ceftaroline or ceftobiprole, you just need to think, “Oh, those are 5th gen. They’re the only cephalosporins that cover MRSA.”
- They can be used, same as 3rd and 4th gen, for broad-spectrum nosocomial coverage in combination with vanc.
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