I have a patient who, after a bout in ICU and after 3 weeks of hospitalization, had Candida albicans growing in the urine (with no flank pain, or urinary urgency or discomfort), and also on her central venous catheter tip (only growing in 1 of 2 bottles). She has a Foley in and suffers from urinary incontinence. She also presents with symptoms of an URTI (query HAP query COPDE) However, blood cultures are negative in all bottles. Do you treat with fluconazole?
Risk factors for candiduria: elderly, female, indwelling urinary device, on broad-spectrum ABX, diabetes.
IDSA says: if blood cultures are positive, then definitely treat. However, asymptomatic candiduria is NOT treatable unless neutropenic, an infant, or will undergo urologic surgery. In other patients, treatment does NOT affect mortality. Definitely try and pull the Foley!
Data is lacking regarding negative blood cultures and positive cath tip cultures: data from this paper would seem to indicate that you would NOT treat just a positive cath tip culture. Given that this patient also does not present with symptoms of a UTI (she has urinary incontinence at baseline), it would seem that fluconazole treatment is NOT warranted.
UPDATE (Oct 21): so I found out that it is “common practice” to treat for 2 weeks after central catheter removal with an echinocandin (if you don’t know it’s an azole-susceptible Candida sp.) or fluconazole (if indeed Candida albicans). I guess it is playing it safe – catheter tip in the blood…treat AS IF it is a candidemia.
Osteomyelitis XR and CT “language”
– “Periosteal reaction” = usually means new bone is growing from destructed old bone due to either injury or infection
– “Osteolysis” = can be from inflammatory etiology or malignancy
– “Subperiosteal abscess” or “subcutaneous gas” = anaerobic involvement
In diabetic patients only, a probe to bone of an infected wound automatically means that the patient has osteomyelitis. No imaging is necessary.
Also learned that wound care nurses can be your best friend on an ID or AMS service…look for the “wet ones” to be infected, and “dry eschar” or the like to be infection mimics! Of course though, always correlate with clinical status and imaging.
Few things learned today…
Causative organisms and imaging
– Staphylococcus aureus is not a common cause of CAP, but one is at higher risk if a patient had influenza prior to developing a pneumonia
– S. aureus pneumonia can be correlated with cavitations (indicating an abscess) on a CXR…but then again, cavitations could also reflect group A strep or S. pneumoniae pneumonia.
– Combined with risk factors of course, Pseudomonas aeruginosa pneumonia could be gathered by bronchiectasis on the CXR
Atypical coverage is only warranted if one feels that the host immune system will not be able to overcome such an infection, such as in the case of immunocompromised patients, or those with structural lung disease.
Beta-lactams and coverage of a CAP
– High-dose amoxicillin (1 g PO TID) is only recommended if intermediate Strep is suspected…and local resistance rates indicate that it is not a worry here
– Risk factors for a beta-lactam resistant Strep pneumo: patient <2 or >65 yo, beta-lactam therapy within last 3 months, alcoholism, medical comorbids, immunosuppressed, exposure to child in daycare centre.
– For outpatients only: amoxicillin, amoxi/clav, cefuroxime are all acceptable alternatives. IDSA guidelines recommend adding a macrolide or doxycycline for atypical coverage, but practically, only if immunocompromised or structural lung disease is present.
– For inpatients: cefotaxime, ceftriaxone, ampicillin. Respiratory FQs ONLY USED FOR TRUE BETA-LACTAM ALLERGY.
Haemophilus influenzae can produce beta-lactamases. Which cephalosporins and penicillins overcome these enzymes?
– Cefuroxime is more active than cefazolin to H. influenzae and M. catarrhalis that produce beta-lactamases
– 3rd generation cephalosporins are distinguished by stability against beta-lactamases of Gram-negative bacilli
Ceftaroline is a 5th gen cephalosporin with activity against MRSA, VISA, and S. pnuemoniae resistant to penicillin or CTX. It does NOT cover ESBL, Pseudomonas aeruginosa, Acinetobacter baumanii, or B. fragilis
Upper GI bleeds (UGIB) – I always thought that the colour of the stool is a good indicator of whether it is an UGIB or lower GIB (LGIB). However, I learned that it wasn’t a sensitive indicator, although it can aid in the diagnosis. General management for a non-variceal bleed is as follows:
– IV PPI (increases gastric pH –> stabilizes blood clots –> improves survival). Is intermittent dosing better, or continuous infusion better? This meta-analysis seems to say that there is a 28% RRR (2.64% ARR) for re-bleed within 7 days for intermittent dosing, although the results were pooled from a variety of intermittent regimens.
– Prokinetics: only warranted if endoscopy is needed to rule in or rule out UGIB. Erythromycin 3 mg/kg IV over 20-30 mins, 30-90 mins pre-procedure.
– Somatostatin and octreotide: clinical efficacy proven, but PPIs and prokinetics (with endoscopy) are much cheaper and there is more clinical experience.
Splenic infarcts and abscesses: when are antibiotics indicated?
Splenic INFARCTS: due to a whole bunch of different diseases, such as underlying cancer, embolic disease (such as A-fib or IE), splenomegaly, trauma. Treat the underlying cause.
Splenic ABSCESS: usually results from an endocarditis. May be accompanied by left-sided pleural effusion. This requires drainage + antibiotics +/- splenectomy. Usually the abscess is polymicrobial – usually E coli, Streptococcus spp, Enterococcus spp, and anaerobes.
Currently on project week, but attended a seminar conducted by one of the graduate PharmD candidates on the use of DOACs in valvular A-fib. Personally, I had come across a couple of patients on my 489 rotation and also a patient on Clinical Orientation who had some form of valvular stenosis (don’t recall which valve was affected), and upon further review of an NEJM review paper, I always assumed the following: mechanical valve = no DOACs allowed. These patients were on warfarin or put on warfarin upon discharge. Turns out it is always a bit more complicated than that…here are some highlights:
- The definition of valvular A-fib varies, depending on where you are. In Canada: mitral stenosis, or bioprosthetic/mechanical valves qualify as valvular A-fib.
- The original warfarin vs placebo trials excluded patients with mitral stenosis as warfarin was already standard of care…hence DOAC vs warfarin subgroup analyses that were conducted after RE-LY, ARISTOTLE, ROCKET-AF excluded mitral stenosis pts as well
- The subgroup analyses of the 3 landmark DOAC trials are based on small sample sizes on the scale of n = 200 or so
- The most reassuring data comes from RE-LY and ARISTOTLE in terms of stroke, systemic emboli, and major bleed rates when it comes to testing for interaction between having various forms of valvular disease or not having valvular disease
- Dabigatran = no differences in stroke, emboli, or bleed whether you had valvular disease or not; HOWEVER, the RE-LY re-analysis included patients with moderate and severe mitral stenosis – i.e. the patients more likely to be admitted.
- Rivaroxaban = may have increased bleeds with atrial or mitral regurg…but that may be due to bigger sample size
- Apixaban = no differences in stroke, emboli or bleed whether you have valvular disease or not
- Bottom line: dabigatran appears to have the most reassuring data, with the caveat that atrial regurg or stenosis, or mitral regurg drove the results
- Bottom line: mechanical heart valves still are a no-go for DOACs. Trials are ongoing, however.
After this seminar, it definitely opened my eyes and I would look harder into whether a DOAC can be used, as now current practice appears to be shifting towards being a little looser with their use. Also, as a bonus, Pharmacare coverage can be obtained as long as the valvular disease is not rheumatic in nature, as long as it isn’t mitral stenosis, and as long as it isn’t a prosthetic heart valve.
I notice that quite a few of the patients I have encountered so far in Clinical Orientation and my 1st patient on my Oncology rotation are on SMX/TMP for PCP prophylaxis. It begged the question: when is it warranted? According to this meta-analysis, if the risk is >6%, you give prophylaxis. Which conditions warrant this type of risk? Should all cancer patients receive it?
– Cancer patients who SHOULD receive PCP prophylaxis: HL, NHL, brain tumours, myelodysplasia, ALL, lymphoproliferative dz, or myeloma, relapsed dz, “high-dose” corticosteroids, or R-CHOP-14 regimen
– Treatment with 20 or more mg prednisone equivalent for 1 month or more
– Alemtuzumab or temozolomide recipients
– Allogenic and select autologous (w/purine analogue conditioning Tx) HCT recipients
– Solid organ transplant recipients
There are a few SMX/TMP regimens… DS tab daily, DS tab qMWF, SS tab daily… there isn’t much direction to choose one. There was an RCT in HIV-infected patients that wasn’t statistically significant for daily SMX/TMP, but there was roughly 2x more discontinuation due to ADRs from the daily group.
I’ve personally seen DS tab qMWF most but it all depends on patient-specific factors such as adherence and recent lab work!
When to NOT bridge warfarin with LMWH following a procedure (low risk)
– Laprascopic surgery
– Dermatologic procedures
– Ophthalmologic procedures
– Bone marrow aspirate and biopsy, lumbar punctures
CSF findings that would raise suspicion of viral encephalitis (not meningitis)
– Increased WBC but <250/mL
– Increased protein but <150 mg/dL
– Normal glucose (decreased with herpes simplex)
– RBC usually absent, but positive in HSV-1 or if contaminants present
Gram-negative bacilli may be divided into fermenters and non-fermenters.
Fermenters can be found in GI/GU: E. coli, Proteus mirabilis, Klebsiella spp.
Non-fermenters (skin, resp, GU): Pseudomonas aeruginosa, Acinetobacter spp., Legionella pneumophila
Acinetobacter susceptibilities follow Pseudomonas susceptibilities closely!
And while I’m at it..
– Neisseria gonorrhoeae
– Neisseria meningitidis
– Moraxella catarrhalis
– Haemophilus influenzae
Some causes of an elevated lactate include:
– Decreased renal function
– Comorbid liver disease
– Decreased tissue perfusion, hemodynamic instability (like sepsis)
– Active alcohol abuse
– Decompensated HF
– Hypoxic state
Myelodysplastic syndromes – risk and prognosis measured by DIPSS score, taking into account (one point each): age >65 yo, leukocytes >25, Plts <100, required transfusion, circulating blasts 1% or above, unfavourable karyotype, fever/sweats/wt loss preceding Dx. High risk DIPSS is for a score of 3 or above.
– DIPSS factors into decision making for drug therapy. High risk = allogenic HCT is favoured. Low risk = symptomatic care such as DNA hypomethylating agents, transfusion, G-CSF, or darbepoeitin may be favoured.
– Iron chelation therapy post-transfusion initiated if ferritin is constantly elevated >1000, AND pt is stable (no comorbid infections), DIPSS low risk (0-1) may favour iron chelation.
Few tidbits from the ADS on ID.
- Presence of polymorphonuclear cells (PMNs) indicates inflammation
- Beware of epithelial cell contamination in a sample
- Coagulase-negative Staphylococcus spp is often a contaminant of blood cultures
- A C&S will NEVER have PO susceptibility data due to concerns with bioavailability. Consult microbiology if you need direction.
- Eosinophilia increases suspicion of allergic reactions or parasitic infections
- Lymphocytosis increases suspicion of malignancy or bacterial infections
- Acute phase reactants are non-specific but add to the overall picture
- Pearl: cellulitis treated with ABX will appear to worsen for 2-3 days due to killing of bacteria and subsequent release of endotoxins
- Some antibiotics perform poorly in acidic environments, so therefore will not penetrate and treat an abscess.
- When do you consult microbiology?
- Need more specific identification on an organism
- Need additional susceptibility or MIC data
- Need guidance on which test to use to identify a bug
And of course, this fun gem:
I found this one to be interesting, and involved some digging into EMR. The patient was in for C. difficile associated diarrhea (CDAD), and was the first instance that I could see on Meditech (since 2010 at least), and was on vancomycin 125 mg PO QID since the 28th (closing in on one week). The order read as follows:
vancomycin 125 mg PO TID x 2 days (starting Jul 5th) then
vancomycin 125 mg PO BID x 3 days then
vancomycin 125 mg PO daily x 2 days then stop.
Immediately I thought that I better look into it as I was unfamiliar with taper regimens for PO vancomycin. What I found was that there really is not that much evidence to support taper regimens despite it appearing on UpToDate and some clinical guidelines, and taper regimens are only recommended under guidelines for the 2nd recurrence. In addition, it was the patient’s first bout with C. difficile as far as we knew; in that case what is recommended is either metronidazole 500 mg PO TID or vancomycin 125 mg PO QID x 14 days, if severe (see the paper above for more details). I decided to write it in the clinical book that the pharmacy had, describing my concerns so that the clinical pharmacist could reassess and follow up. It was a good opportunity to delve a bit deeper into an order and try and make an intervention from the dispensary.
For this Nugget of Knowledge, I put several tags on it because I think I will be referring to it on multiple rotations…I just picked the ones that I suspect it will come in most handy.
Probably not the first thing that comes to mind when one thinks about drug distribution, but always a thing to keep in mind on a dispensary shift if a patient is on a bunch of QT prolonging drugs – how do you know who is at higher risk than another? Today I attended a CSHP webinar on this very topic; here are some pearls I picked up:
FDA and Health Canada definition of a prolonged QTc
>500 ms OR >60 ms above baseline
Beware of the hypos – K, Mg, and Ca
Risk stratification tool #1 – Tisdale et al – validated in cardiac critical care units
– Assigns varying point values to different risk factors
– Offending DRUGS are given more weight than say, hypokalemia
– Great positive predictive value for high risk individuals
– They did not routinely measure magnesium levels
– However, only predicts risk of prolonged QT, NOT TdP or any hard outcomes such as mortality.
Risk stratification tool #2 – Haugaa et al with the Mayo Clinic – not validated, but had patients across the board: peds, medicine, cardiology, ICU, you name it
– EQUAL weighing of risk factors
– Hard outcome: mortality
– Good predictive value of mortality for scores 4 or above
– ONLY valid for baseline QTc of 500 ms or greater
These tools are great for stratifying patients according to risk and will help me prioritize interventions. As always I would perform NESA on each offending drug (or each option to treat a condition) to see if it is worth the risk. Also, downloaded the CredibleMeds app onto my phone – a great tool to quickly look up rough risk levels for various medications to prolong the QT interval.