Meet Mr. IP Bugs

This past week has been crazy! I did a management conference [AKA doing a 15 minute presentation in front of a bunch of pharmacists who knew more than I did ;)] and a journal club today. Both were 'first-timers' for me. Although the management conference was a bit intimidating, I'm really happy they have us do it on this rotation. My topic was on UTIs, and I wanted to share what I learned, among other things since last Monday.

Infectious
So, Mr. IP Bugs is an 85 y/o male patient who presents with a UTI. He denies hematuria, dysuria, N/V, fever, and urinary frequency. He has a beta-lactam allergy documented as 'swelling all over the body' with penicillin. His urine culture grew 3 bugs: acinetobacter and 2 species of enterococcus. The team wanted to start him on just one medication to cover all three bugs. The best option, considering susceptibility results, was ciprofloxacin. However, one of the enterococcus strains had an intermediate susceptibility to cipro, and the team was recommended against starting cipro on this patient. Quick review on sensitivity results: Usually done by minimum inhibitory concentrations (MIC), and recall that the smaller this number is, the more susceptible a bug is to a certain drug, since it takes less drug to kill the bacteria. So, therapy for infectious diseases sometimes deals with getting the blood concentration of the drug to concentrations above the MIC. Now, in UTIs, the debate is whether it's sufficient just to get the drug concentrations in the urine above MIC (since renally excreted drugs will concentrate in the urine). It makes sense if you think about it, and I actually found some studies done that show that treating certain kinds of UTIs don't have to correlate with inhibitory drug concentrations in the blood. What kinds of UTIs? What I found was lower UTIs. Now as we go higher up the urinary tract to the ureter and kidneys, it's necessary to have inhibitory drug concentrations in the blood. There's a  review article I read that said with a dose of 500mg PO of cipro, the blood concentration of the drug was 1.6-2.9mg/L and urine concentration was 350mg/L *ding ding ding!* The patient's MIC values for his 3 isolates to cipro were about 1-3mg/L. In this case, the urine concentration that a 500mg dose of cipro results in (350mg/L) is much greater than the patient's MIC values (1-3mg/L). I would argue that cipro could be used in this patient! What actually happened - the patient had to be started on amiodarone for his A-fib (cipro + amio = prolonged QT interval), so he was D/C with other antibiotics for his UTI. This urine vs. serum concentration debate can be extended other drugs and lower UTIs as well.

Hyperlipidemia
The update regarding high dose simvastatin (80mg) recently was to NOT recommend it to new patients due to increased incidence of rhabdomyolysis (which can lead to kidney failure). However, if a patient has already been on this dose for at least 12 months without any myopathy, then this dose is okay. I saw a severe ADR from simvastatin this past week. The patient's creatine kinase (CK) level was about 800, and upper limit of normal (ULN) is about 120. The team was encouraged to decrease the dose of the statin (the patient couldn't be D/C'd completely since he recently had an MI).

Hypertension
There's an interesting class of drugs that can be used to treat hypertension: the alpha1 blockers. These include prazosin, terazosin, and doxazosin. They are also used to treat HTN, BPH, and PTSD (only prazosin for the latter since it crosses the blood brain barrier). If either of these 3 drugs cause orthostatic hypotension, then tamsulosin is used as a back up. Also in relation to HTN, we learned the distinction between HTN emergency and HTN urgency. If a patient's systolic blood pressure goes above 180 OR the diastolic blood pressure goes above 110, then it's consider EITHER HTN emergency OR urgency. The thing that separates these two diagnoses is that HTN emergency has end organ damage as well. With HTN emergency, the common treatments are nifedipine, esmolol, labetolol, diltiazem, and nitroprusside (beware of cyanide toxicity...see picture). These are all drugs of choice because of their fast acting nature.

Look at all those cyanides!

Anticoagulation
My preceptor taught me about certain things to look for when deciding the dose of an anticoagulant to give to a patient. This is important stuff, because this is the fine line between a bleed and a clot. So, first decide whether we're putting the patient on a treatment dose or a prophylaxis dose. For a treatment dose, it's for patients with a recent DVT and a CHADS score of about 4-6. For these patients, you would want to consider direct thrombin inhibitors such as bivalrudin, lepirudin, and argatroban. For a prophylaxis dose, it's for patients with a DVT in the distant past and a lower CHADS score. For these patients, fondaparinux (don't use if CrCl <30ml/min) would be an appropriate choice. Moving onto HITT (heparin-induced thrombocytopenia and thrombus)...what a tricky situation. The patient has a thrombus, so you need to give some kind of blood thinner, and heparin is obviously out of the question...warfarin takes a few days to work, what are the options? In this case, fonda, bivalrudin (0.75mg/kg bolus, 0.25mg/kg/hr infusion), lepirudin, and argatroban (2mcg/kg/min) can be used. Argatroban would be the first choice in this case. Use of lepirudin apparently increases antibodies in your body against the drug, so if there's a history of lepirudin use, may not be a good idea to use it again. An important thing to note with argatroban is that it increases the INR (although the pTT is the monitoring value for argatroban). In such cases of HITT, warfarin is started once platelets reach >150K, and oftentimes while argatroban is still being given. This combination should be continued for 4-5 days, but with INR monitoring (sometimes INR>5 will be seen without risk of major bleed).

That's all from a few days last week...correct me if I didn't quite get something right :)