* Most common cause of pyelonephritis is E. coli, most common cause of osteomyelitis is S. aureus. * So what antibiotics go along with staph/strep, gram negative rods, and anaerobes?
* If you do PCR resting on Egyptian mummies from 5 thousand years ago, you will find there was beta-lactamase in the staphylococcus.
* Ampicillin, penicillin, amoxicillin alone is good for streptococcus, but not for staphylococcus.
* Antibiotics for staphylococcus and streptococcus are oxacillin, cloxacillin, dicloxacillin, nafcillin (not methicillin). * With methicillin-sensitive staphylococcus, what do you use? Not methicillin. Use ox, clox, diclox, naf. Why don’t we use methicillin? Because it causes interstitial nephritis.
* Another alternative for staphylococcus and streptococcus (e.g. penicillin allergy) is a beta-lactam drug, first- generation cephalosporins like cephalexin, cephadroxil, cefazolin. 5% cross-reaction with penicillins at most and almost never anaphylaxis, so don’t worry if the allergy is a little rash.
* What if patient says they have a penicillin allergy, that causes a little rash, and hypotension, and stridor, and laryngeal edema so they had to get intubated, then got IV steroids, then dopamine drip in the ICU. For life- threatening penicillin allergies, then we should avoid all the beta-lactam antibiotics.
* Macrolides: erythromycin, azithromycin, clarithromycin. Macrolides with clindamycin will cover staph/strep, but are not first choice, choice for life-threatening penicillin allergy. Vancomycin works, but should be reserved for methicillin-resistant staph aureus (MRSA). Vancomycin not superior in efficacy to ox/clox/diclox/naf, just superior in its resistance pattern.
* Gram negative rods include E. coli, klebsiella, proteus, enterobacter, citrobacter, pseudomonas.
* Antibiotics for Gram-negative rods are aztreonam, aminoglycosides (gentamycin, streptomycin, tobramycin, neomycin, amikacin), fluoroquinolones (ciprofloxacin, levofloxacin, trovafloxacin, gatifloxacin, sparfloxacin, moxifloxacin), second-generation cephalosporins (will not cover pseudomonas), third-generation cephalosporins (ceftazidime, ceftriaxone), carbapenems (imipenem, meropenem), extended spectrum penicillins (piperacillin, ticarcillin, azlocillin, mezlocillin).
* Carbapenems cover Gram-negative and Gram-positive, but you should not use them for Gram-positive infections (like strep throat) because there are better drugs exclusively for Gram-positives. “Do not swat a fly on your friend’s head with a hammer.”
* TMP-SMX is only good for uncomplicated cystitis and prophylaxis against pneumocystis pneumonia. * Chloramphenicol is never the right answer, it causes aplastic anemia and Gray Baby Syndrome.
* Cephalosporins range from strong Gram-positive coverage at first-generation (poor Gram-negative) to strong Gram-negative coverage at third-generation (poor Gram-positive). Fourth-generation cephalosporins (cefepime) are a combination of first-generation and third-generation, so they cover Gram-positives and Gram-negatives.
* Antibiotics for anaerobes are metronidazole (particularly good for abdominal), clindamycin (does not cover bowel well), carbapenems as well. If you have an exclusively anaerobic infection, don’t jump to imipenem.
* Tetracycline is not the correct choice anymore; use doxycycline instead. Doxycycline used for Lyme (mild disease: rash, facial nerve palsy), Chlamydia, rickettsia, as these are intracellular organisms.
* Nitrofurantoin used for UTI in pregnancy, no other use.
--- Meningitis
* 57yo man comes to the ED with fever and a headache. Photophobia or seizures or nausea or vomiting are too non- specific here. A specific additional symptom to lead you down the right path would be stiff neck (nuchal rigidity), implying meningitis. What if they want you to know it’s a brain abscess? Fever, headache, and focal findings. What about encephalitis? Fever, headache, altered mental status (confusion, encephalopathy).
* So 57yo man has fever, headache, stiff neck. What is the first test? Do you do a lumbar puncture or a CT scan? What is the first test? Lumbar puncture (LP). Only do a CT scan prior to a spinal tap if papilledema or focal findings that would imply a brain mass/abscess. Patient also needs to be able to follow commands, such as “squeeze my hands,” because you cannot determine focality. If you had a mass lesion that was so small it did not cause focality, an LP would not cause herniation.
* If you are going to do a CT prior to the LP, you should start the patient on antibiotics first (dose of ceftriaxone). Doesn’t that ruin the sensitivity of the LP culture? Yes, but you’d rather be alive with a clean LP than dead with an accurate LP. Other information from the LP can help tell you the diagnosis.
* The most common neurologic problem after meningitis is deftness, CN VIII damage, it can happen within hours. * With papilledema you worry about herniation. “You go to do a rectal later and say ‘my that’s a smooth prostate’ and the patient says, ‘that’s not my prostate, that’s my pons.’”
* When you have infectious diseases, what is the most accurate diagnostic test? Answer is culture. All other tests are compared to culture. When do you wait for results of the culture? Never.
* CSF analysis: Which form of meningitis can give an elevated protein and decreased glucose in the LP? Answer is all. Which gives it most often? Bacterial, strep pneumonia. Gram-stain is 50-60% sensitive, so won’t be positive most of the time. So what will tell you right now what type of organism you have? Answer is cell count.
* CSF cell count: Only bacterial gives you 1000s of polys, where others give 10-100s of lymphocytes. If you see 1000s of polys, give ceftriaxone. What about 10-100s of lymphocytes? Could be fungal (cryptococcus), Rocky Mountain Spotted Fever, Lyme disease, syphilis, tuberculosis, viral meningitis.
* For cryptococcus meningitis, expect HIV patient with < 50 CD4 T-cell count. Best initial test? Answer is not India Ink. However, India Ink is about 50% sensitivity (good if positive, means nothing if negative). Answer is
cryptococcal antigen testing, positive in 95-98%, very sensitive and specific. Should you start this patient with fluconazole? No, use amphotericin B. Amphotericin B (better than fluconazole for saving life in meningitis), then follow up with fluconazole forever. Fluconazole is continued life-long, else cryptococcal meningitis recurs.
* Rocky Mountain Spotted Fever (RMSF) is not seen on Gram stain because it is intracellular (rickettsia). Lyme also not seen on Gram stain because it is a spirochete. You also can’t see TB, viral, Legionella, or syphilis on Gram stain. * So, CSF from lumbar puncture shows 10-100s of lymphocytes, Gram stain negative, culture negative. Now what? Answer is serologic testing to look for specific antibody against Lyme and RMSF. This helps you determine if you should use doxycycline or ceftriaxone. So this is very easy, right? We just get some IgM acutely and IgG
* So are with “atypical” results (Gram stain negative, culture negative), are we just going to order Lyme, RMSF, cryptococcal antigen testing, AFB (acid-fast bacillus) stain and culture, viral serologic testing, syphilis serology with a VDRL and FTA on all of them? Nope. You have to suspect the specific disease.
* If RMSF, centripetal (moves centrally) rash and outdoor activity. If Lyme, target rash (erythema migrans) and outdoor activity. Lyme in Connecticut, Massachusetts, New York, New Jersey (North East). RMSF in Alabama, Kentucky, Tennessee, Carolina, it shouldn’t matter, look for the centripetal rash. If TB, diagnose with TB stain and AFB cultures. If viral, diagnosis is by exclusion of the others, there is no treatment.
* Test TB (meningitis and pulmonary) with TB stain, TB culture, INH, rifampin, pyrazinamide, ethambutol. * When do you answer steroids for meningitis in adults? Answer is TB meningitis. Some mild benefit possibly with steroids given prior to starting antibiotics and LP.
* When do you answer intrathecal antibiotics? Answer is never, not necessary. Methotrexate is given intrathecal in ALL (acute lymphoblastic leukemia). Intrathecal antibiotics is like intra-cardiac epinephrine, nifty idea but not necessary.
* Elderly neonate is HIV positive, on steroids for CLL, has a lumbar puncture with elevated protein and decreased glucose, Gram stain negative, 3200 polys. What is the next best step in the management of this patient? Do we give amphotericin or ceftriaxone? HIV is a risk factor for fungal meningitis. This isn’t fungal because there are polys present. This patient is immunocompromised. So what organism do we have to cover? Answer is listeria. Answer for management is give ceftriaxone and ampicillin, because listeria is resistant to all forms of cephalosporins. * Things that put you are risk for listeria include immunocompromised, neutrophil and T-cell defects, HIV (T-cell defect), steroids (neutrophil and T-cell defect), leukemia/lymphoma elderly or neonate then do empiric coverage. --- Encephalitis
* Fever, headache, and confusion (encephalopathy). What is the next step? Head CT. The head CT will most likely be normal. Lots of encephalitis in the world, eastern equine encephalitis, western equine encephalitis, Colorado tick fever, Congo Crimean fever, Venezuelan hemorrhagic fever, Bolivian hemorrhagic fever, viral encephalitis. * If you add all those cause of encephalitis and multiply by ten, they still are not as common as herpes encephalitis. If the case is clearly encephalitis and they ask diagnosis, your best bet is to answer herpes.
* Lumbar puncture should come with PCR, which has largely replaced the biopsy. What is suggestive of herpes on a lumbar puncture? Answer is increased red cells, mildly hemorrhagic. How do you know it is not a subarachnoid hemorrhage? There will also be increased WBCs from infection, plus clear CT scan favors against subarachnoid. * Treatment of herpes encephalitis is acyclovir.
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