Sulfamethoxazole/trimethoprim and increase in serum creatinine: When to be concerned

A 65 year old male is being treated for an infection on his forearm that developed purulent drainage within the last few days.  He denies experiencing any penetrating trauma to his arm and denies any other complaints at this time.  He weighs 70 kg, His WBC count is 14.7 x 109/L, serum creatinine is 1.3 mg/dL, and his vital signs are within normal limits.  His past medical history includes hypertension and an MRSA infection last year.  He is currently taking valsartan 160 mg daily and chlorthalidone

Inhaled isopropyl alcohol for nausea

An elderly male presents to the emergency department with complaints of nausea, vomiting, and diarrhea starting a day and a half ago.  The diarrhea started abruptly, has occurred almost 10 times, and is non-bloody.  His abdomen is soft but has mild diffuse tenderness.  Vital signs and basic laboratory results are normal except for a potassium of 2.9 mEq/L and an EKG with a QTc interval of 490 msec. 

Nitrofurantoin in renal impairment

A 74 year old female patient presents to clinic describing dysuria and urinary frequency that started within the last few days.  She has no vaginal discharge or irritation and has no CVA tenderness, fevers, chills, flank pain, nausea, or vomiting.  The diagnosis of uncomplicated UTI is made based on clinical suspicion and you decide to prescribe some antibiotics.  She weighs 72 kg and her SCr is 1.4 mg/dL.  Using the Cockcroft-Gault equation,

Pneumococcal vaccine: Which, when, and why?

The pneumococcal vaccine was developed to reduce the disease burden of streptococcus pneumoniae, a gram-postive bacteria that has more than 90 serotypes that can cause diseases in humans.  Some of these infections include pneumonia, meningitis, bacteremia, otitis media, and sinusitis.  There are currently two vaccines on the market to raise immunity against pneumococcal infections - PCV13 (Prevnar 13 - which covers 13 serotypes) and PPSV23 (Pneumovax 23 - which covers 23 serotypes).  The 23-valent vaccine covers all of the serotypes in the

"How it works" series: Daptomycin

Daptomycin (Cubicin) is the first antibiotic in a class known as lipopeptides and has a unique mechanism of action.  Daptomycin is a large molecule with a high molecular weight and has two distinct sections.  One section is a 10 member amino acid ring (illustrated as the big red circle) and the other is the attached lipophilic tail (illustrated as the curvy red line).  The lipophilic tail is capable of direct insertion through the

Linezolid-induced thrombocytopenia

Thrombocytopenia is a notable adverse effect of linezolid.  Some of the evidence behind the onset, duration, and the extent of platelet decrease will briefly be described here and summarized in bullets at the bottom of the discussion.  For a discussion of linezolid's mechanism of action and some other notable features, see a prior post here.

Intrapleural tPA and dornase alfa for pleural infection

A 48 year old male is admitted to the hospital after experiencing a fever and malaise for several days.  He states that he has some shortness of breath and chest pain when he coughs.  Imaging of the chest reveals a large loculated effusion and empyema in the right lower lung.  The decision is made to place a chest tube (thoracostomy) and drain the fluid.  The pleural fluid returns with a pH of 7.18, a glucose of 55 mg/dL, and a lactate of 1,150 units/L.  Initial drainage was 200 mL in the first 24 hours, contained pus, and had a putrid odor.  Cultures are pending.  In addition to drainage and appropriate antibiotic therapy, what else can be done to manage this patient?

"How it works" series: Vancomycin

(Click to enlarge)

Vancomycin was the first antibiotic developed of the glycopeptide class.  It is termed "glyco-" because it has two saccharides and "peptide" because it has seven peptides, making a structure larger than almost all other antibiotics.  The main mechanism of action is inhibition of cell wall synthesis.  Under normal conditions in bacteria, as the cell wall is being formed,

"How it works" series: Linezolid

Linezolid (Zyvox) is one of only two antibiotics currently on the market in the oxazolidinone class (see what the other one is at the bottom of this article).  The unique structure makes cross resistance to other antibiotics like beta-lactams or vancomycin unlikely.  It works by binding to the 50S subunit of ribosomes in bacteria, preventing it from joining its partner 30S subunit.  In stopping the 50S subunit from binding the 30S subunit, the completed complex (70S) is never formed and therefore cannot begin to

Legionnaires' disease - reliability of urine antigen testing

A 58 year old male patient presents to the emergency room with shortness of breath for the last few days.  He also complains of chills, a cough, myalgia, and diarrhea.  His notable findings include WBC = 14 k/uL, Scr = 1.2 mg/dL, BUN = 27 mg/dL, BP = 132/76 mm Hg, RR = 30 breaths/minute, Tmax = 38.5⁰C, and O2sat = 92% on room air.  His chest x-ray reveals a patchy infiltrate suggestive of pneumonia.  Upon further questioning, the patient tells you he lives across the street from an apartment building where several people recently were diagnosed with Legionnaires' disease.  He has no recent exposure to any health care settings, has taken no antibiotics, was not recently incarcerated, is not immunocompromised, and has not recently traveled.  Can we use urine antigen testing to help guide our treatment of this patient's pneumonia?

Use of cephalosporins in penicillin-allergic patients

Let's start with a patient case.  A 71 year old patient arrives to the emergency room complaining of shortness of breath and sputum production that has worsened from when it started about three days ago.  She has a past medical history of diabetes mellitus type 2, myasthenia gravis, and atrial fibrillation and is taking metformin, pyridostigmine, prednisone, warfarin, and sotalol.  Her BP = 132/88, HR = 78, RR = 24, and T = 37.5 C and CXR reveals a left lower lobe infiltrate.  The diagnosis of pneumonia is made and as you begin to type orders for your standard ceftriaxone/azithromycin combination, you note that the patient has a penicillin allergy.  What is the risk of continuing this antibiotic regimen given the patient's allergy?

Risk of peripheral neuropathy with fluoroquinolones

Last year, the FDA issued a drug safety communication, warning about the risk of nerve damage from fluoroquinolone antibiotics.  You can read last year's post about the warning and other information on fluoroquinolones here: Serious peripheral neuropathy and fluoroquinolones.  

Interpreting minimum inhibitory concentrations

Several previous discussions have dealt with the concept of the minimum inhibitory concentration (MIC) such as extended-infusion piperacillin/tazobactam (Zosyn) and vancomycin dosing in hemodialysis.  Though this concept was learned at some point, questions occasionally arise as to what these numbers represent and what to make of them when they show up on a culture and sensitivity result.  This post will discuss the MIC and hopefully address some common misconceptions.  For the take home points, skip down to the bullets at the end.

Doxycycline food and OTC interactions

Since it's the time of year again when Lyme disease is a concern for patients in many parts of the United States, I thought it would be good to discuss one issue concerning doxycycline.  Doxycycline is a preferred oral agent for Lyme disease and many of its complications.  It is recommended for a variety of situations when Lyme disease is suspected or confirmed such as1:

• Single dose prophylaxis after tick bite
• Erythema migrans
• Cranial nerve palsy
• Carditis
• Lyme arthritis
• Acrodermatitis chronica atrophicans
• Co-infection with human granulocytic anaplasmosis

When ordering or verifying the typical adult dose of 100 mg orally twice daily, an alert may pop up for an interaction with several drugs including iron, calcium, magnesium, aluminum, or bismuth subsalicylate.  The proposed mechanism for this interaction is chelation in the gastrointestinal tract, compounded by the enterohepatic circulation of doxycycline.  Let's look at some of the data regarding these interactions.

More cardiovascular safety data for azithromycin

There has been concern in recent years regarding cardiovascular risk in patients using azithromycin which I discussed in an earlier post found here.

A recent study in JAMA further examined cardiovascular risk and mortality in a retrospective review of more than 60,000 patients in the VA Health System.  This study specifically identified patients with a diagnosis of pneumonia who were treated with antibiotics including azithromycin compared to other guideline-concordant antibiotics.  Their outcomes of measure were 30-day mortality, 90-day mortality, any cardiovascular event, myocardial infarction, heart failure, or cardiac arrhythmias.  The mean patient age was 78 years old and comorbid conditions were fairly common (35% with diabetes, 52% with COPD, 26% with heart failure).

Piperacillin-tazobactam (Zosyn) extended-infusion dosing

Let's start with a patient case.  A 70 year old male patient is admitted to the hospital for a diabetic foot infection.  He has a past medical history of HTN, hyperlipidemia, CKD, gout, and obesity.  He weighs 100 kg and has a Scr of 2.8 mg/dL.  You recall that piperacillin-tazobactam is indicated for diabetic foot infections and are deciding what dosing regimen should be started.  Upon consulting Lexicomp or Micromedex, you will find that piperacillin-tazobactam has a wide dosing range depending on the type of infection being treated in addition to the extent of renal impairment.  Recommended doses range from 2.25 g to 4.5 g intravenously every 6 to 12 hours depending on these factors, leaving much room for uncertainty in many cases.

The following will briefly discuss piperacillin-tazobactam, its pharmacokinetics and pharmacodynamics, and how computer modeling has generated new dosing strategies.  If you just want a simplified way of dosing this medication, feel free to skip down to the 'Take home pearls' at the bottom of the article.

“Sulfa” allergy cross-reactivity

Let’s start with a patient scenario.  A patient presents to the emergency room experiencing a heart failure exacerbation.  When entering the order for intravenous diuretics, you note that a cross-reactivity warning has popped up for a “sulfa” allergy.  What evidence is there for cross-reactivity between Loop diuretics and “sulfa” allergy and how should this affect your decision?

Vancomycin dosing and monitoring in hemodialysis

Let's start with a patient case.  A patient on hemodialysis (M/W/F) is admitted to the hospital with cellulitis who also meets sepsis criteria.  He has a history of an MRSA infection during a previous admission so you want to initiate vancomycin at this time.  The patient is 76 kg and still makes some urine.  What dosing strategy should you choose and when/should vancomycin concentrations be monitored?

Prevention of postherpetic neuralgia

An elderly patient is admitted to the internal medicine service with a diagnosis of herpes zoster infection in the typical dermatomal distribution.  The patient’s rash is currently not very painful (2/10) but she is concerned about long-lasting pain as her friend had pain from zoster that lasted for months.  What can we use to prevent the development of postherpetic neuralgia?

Postherpetic neuralgia is a common complication of herpes zoster infection and can be challenging to treat.  Drugs approved by the FDA to treat postherpetic neuralgia include pregabalin (Lyrica), gabapentin (Neurontin), and capsaicin patch (high-concentration patch - Qutenza).  Other medications that have been shown in randomized controlled trials to also reduce pain from postherpetic neuralgia include topical lidocaine, tricyclic antidepressants (eg. nortriptyline), opioids, and tramadol¹. 

No medication has been approved for the prevention of postherpetic neuralgia but here is the data on several agents that have been studied:

Azithromycin and cardiovascular risk

Since 2012, the FDA has made two statements regarding the safety of azithromycin related to cardiovascular risk.  These warnings were largely in response to an observational cohort study that found a small absolute increase in cardiovascular deaths in patients receiving azithromycin versus those receiving amoxicillin or no antibiotic in a Tennessee Medicaid population¹.  This excess risk varied based on patients’ baseline cardiovascular risk and was found to be highest in the highest decile of cardiovascular risk.  While a warning from the FDA does seem concerning, it is important to examine some of the details of the data.

• Of the 347,795 azithromycin prescriptions in the study cohort, there were 29 cardiovascular deaths (absolute risk = 0.008%)
• Of the 1,391,180 matched controls, there were 41 cardiovascular deaths (absolute risk = 0.003%)
• These above cardiovascular deaths occurred during the five day treatment course, whereas the analysis that also included the following five days had no difference in death from any cause
• 4,082 prescriptions would have to be used in patients at the highest cardiovascular risk decile to cause one additional cardiovascular death