Fluoroquinolones: An Effective Drug with a Growing Bad Reputation

Evidence: Because the risk of these serious side effects generally outweighs the benefits for selected patients, the FDA has determined that fluoroquinolones should be reserved for use in patients with serious bacterial infections, including anthrax, plague and bacterial pneumonia among others.

Pearl: Side Effects Include: Increased risk of tendinitis and tendon rupture, Increased risk of C-Diff Colitis, Potential for irreversible peripheral neuropathy, Increased risk of aortic dissections or rupture of an aortic aneurysm, Increased risk of fatal hypoglycemia occurring more frequently in the elderly and those taking oral hypoglycemics or insulin, Increased risk of disorientation, agitation, and delirium

Long Term ACE-I Use Associated with Increased Risk of Lung Cancer

Evidence: Researchers followed a cohort of over 990,000 UK patients newly started on anti-hypertensives for an average of 6.4 years and found that use of ACE-I was associated with a modestly increased risk of lung cancer compared with ARBs (1.6 vs 1.2 per 1000 person years, HR 1.14). There is a cumulative effect and the risk increases with duration of use beyond the initial 5 years (HR up to 1.31 for >10 years of use). The possible explanation for this association is that ACE-I causes accumulation of bradykinin in the lung, which has been reported to stimulate lung cancer growth. ACE-I also increases substance P, which is expressed in lung cancer tissue and linked to tumor proliferation and angiogenesis.

Pearl: The link between long term ACE-I use and increased risk of lung cancer seems to be a plausible one. Keep this association in mind when starting patients on new anti-hypertensives, especially in young patients. Educate patients regarding the risks and benefits ACE-I therapy.

Tramadol - A Truly Unpredictable Drug

Evidence: Tramadol is a SNRI which interferes with pain pathways. It is metabolized to ODT, a mu-1 agonist, like opioids. The conversion from SNRI to ODT is done by CYP2D6, which has a wide variation in function across patient populations, making it difficult to assess how a patient will respond. Population of Ethiopians and Saudia Arabians are rapid metabolizers via CYP2D6 (causing increased opiate affect) while those in Scandinavia appear to have a slower metabolism (causing more SNRI effect). Multiple common medications can block the CYP2D6 enzyme and can even precipitate opioid withdrawal in patients taking tramadol. In patients with CKD, the drug interactions are particularly important as patients on dialysis take an average of 19 pills per day. More concerning, among patients aged 50 years and older with osteoarthritis, tramadol was associated with a significantly higher rate of mortality over 1 year of follow-up compared with commonly prescribed non-steroidal anti-inflammatory drugs.

Pearl: Medications that can block CYP2D6 include bupropion, haldol, fluoxetine, amiodarone, and cinacalcet. Tramadol can cause serotonin syndrome when taken with other serotonergic medications. Other significant risks include increased seizures and hypoglycemia. In patients >50 years old with osteoarthritis, tramadol was associated with a mortality rate than NSAIDs.

The Curbsiders JAMA Semin Dial
Cardiovascular Risks of Uloric (Febuxostat)

Evidence: Patients with gout have increased cardiovascular risk. Febuxostat, a nonpurine xanthine oxidase inhibitor, is more effective at lowering uric acid levels when compared to allopurinol. The Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) study, a multi-center, randomized, double-blind, non inferiority trial compared cardiovascular outcomes associated with febuxostat and allopurinol in patients with gout and cardiovascular disease. The study showed in patients with gout and major cardiovascular coexisting conditions, febuxostat was shown to have an increased cardiovascular and all-cause mortality. Following the CARES study, the FDA issued a box warning for febuxostat in 2019.

Pearl: Febuxostat should be reserved for patients who have failed or cannot tolerate allopurinol. When prescribing febuxostat, the associated CV risks should be discussed with the patient. Patients who are on febuxostat should be monitored for cardiovascular signs and symptoms.

Diverticulitis: Clinical Practice

Evidence: Colonic diverticulitis is an inflammatory process that most commonly affects the sigmoid colon. Diverticulitis is inflammation of diverticula and can be either uncomplicated or complicated (i.e., associated with abscess, fistula, stricture, or perforation and peritonitis). Rates of diverticulitis are increasing in association with increasing rates of obesity. Most cases are straightforward for hospitalists to manage but there are helpful clinical pearls surrounding outpatient management and patient education that are highlighted in this article.

Pearl: Simple diverticulitis in the absence of high fever, clinically significant laboratory or radiologic abnormalities, or immunosuppression, can be managed on an outpatient basis. The severity of recurrent episodes of diverticulitis is generally similar to that of the initial episode. Symptoms typically improve within 2-3 days after the initiation of treatment, at which time the diet is commonly advanced to clear liquids and then to a low-residue diet, although data from randomized trials to guide inpatient dietary management is limited. Consultation from nutrition is recommended to supplement physician education. So what the heck is a low residue diet anyways? Limiting high fiber foods (in the initial 1-2 weeks after episode of diverticulitis). 'Residue' is undigested food, including fiber, that makes up stool. The goal is to have fewer, smaller BMs each day. Risk factors for diverticulitis include smoking, the use of nonsteroidal anti-inflammatory drugs, physical inactivity, obesity, diets low in fiber, diets high in refined carbohydrates, and red meat. Evidence does not support the idea that seeds, nuts, and popcorn cause diverticulitis.

Antibiotics for Uncomplicated Appendicitis

Evidence: Multi centric randomized controlled five year observational follow up of 530 patients (ages 18-60) with CT confirmed uncomplicated acute appendicitis, compared appendectomy versus antibiotic therapy. At 5 years the surgical group had a significantly higher overall complication rate (surgical site infections, incisional hernia, abdominal pain) compared to the non-surgical group. About 39% (1/3) of the non-surgical or antibiotic group developed recurrent appendicitis needing surgery, but no complications in the antibiotic group were related to delay in surgery.

Pearl: Long term follow up indicates that antibiotics alone could be a reasonable alternative to surgery in patients with uncomplicated appendicitis. This data provides hospitalists evidence to present to patients and families when reviewing management options. In complicated appendicitis (perforation, appendolith) and in older patients, surgery may still be the best option.

Stress Ulcer Prophylaxis in the ICU

Evidence: A European multi-center RTC of 3298 ICU patients with at least one risk factor for GI bleeding (ie shock, anticoagulation, dialysis, mechanical ventilation, liver disease or coagulopathy) showed there was no difference in 90-day mortality (primary outcome) or incidence of clinically significant GIB, pneumonia, C diff infection or MI (secondary composite outcome) for those initiated on PPI prophylaxis vs placebo. There was a reduced incidence of clinically important GI bleeding (NNT = 59) without causing more infections, however the trial was not powered to address each component of the composite secondary outcome, thus limiting conclusions.

Pearl: The short-term benefits of decreased GI bleeding with PPI use in select ICU patients may outweigh any increased risk of adverse outcomes. Longer term clinical benefit, however, has not been demonstrated and would recommend discontinuing the PPI once leaving the ICU.

Approach Constipation Aggressively

Evidence: At the American College of Gastroenterology Conference 2018, Dr. Melissa Latorre, Director of Inpatient Services for Gastroenterology at NYU, gave an expert talk on her approach to inpatient constipation. She states that “ineffective laxatives, such as docusate sodium, continue to be the most commonly prescribed.” Since the data is very limited, her experience-based approach to inpatient constipation is like chemotherapy with an induction and maintenance regimen. She warns “don’t be fooled by diarrhea,” as it may be overflow, and that it is important to educate nurses and patients that diarrhea is desired upfront.

Pearl: From above: Induction phase: Osmotic laxative like polyethylene glycol 17 g in 8 oz water BID or TID or colonoscopy prep (movi-prep) if patients can tolerate. AVOID fiber, senna, and lactulose upfront as they can exacerbate the symptoms of pain, bloating and distension. Maintenance: Start fiber, increase free water intake, and oral laxatives. Pro-tip: If available – opiate-receptor antagonists are helpful in patients regularly taking opioids. From below: Induction phase: Manual maneuvers and suppositories. Glycerin helps soften stool and bisacodyl helps with rectal motility. After the first BM, provide enemas (mineral oil or tap water) to clean more proximally. Maintenance: Once BMs become reliable, pull back on rectal therapy.

ACP Hospitalist
Things We Do for No Reason: Prescribing Docusate for Constipation

Evidence: Docusate remains widely prescribed despite multiple RCTs that have shown it has no benefit over placebo. Docusate is a detergent that tastes like soap and may decrease oral intake. It delays the initiation of actually effective laxatives and increases pill burden. Effective alternatives supported by evidence include Miralax, Senna, Psyllium, and Lactulose.

Pearl: Stop using docusate! Continue to educate Surgeons and Surgery APNs/PAs to stop ordering docusate.

Things We Do for No Reason: Intermittent Pneumatic Compression (IPC) for Medical Ward Patients

Evidence: The incidence of symptomatic DVT and PE in hospitalized patients is 0.96% and 1.2% and asymptomatic DVT is 1.8%. Studies have shown that IPC reduces the risk for venous thromboembolism in high risk patients including orthopedic, surgical, trauma and stroke patients. The largest systematic meta-analysis of 70 studies and over 16,000 high risk patients concluded reduction in the rates of DVT from 16.7% to 7.3% and PE from 2.8% to 1.2%. However, there is no good data showing efficacy of IPCs in general medical ward patients. IPCs may not be as beneficial for medical ward patients because they are frequently worn or applied improperly, can be a fall risk, and can cause skin irritation and breakdown. Different IPC models have varied efficacy and are expensive.

Pearl: Given the costs, unproven efficacy and possible side effects of IPC in general medicine patients, IPC should not be ordered ordered on general medicine ward patients at low or moderate risk. Combined IPC and pharmacologic prophylaxis should only be used for high risk trauma and surgical patients. IPC alone should ordered only for high risk patients who have a contraindication to pharmacologic prophylaxis. Risk stratification can be assessed by the Three Bucket Model or Padua Prediction Score below.

Things We Do for No Reason
Eliminating Inappropriate Telemetry Monitoring

Evidence: The AHA developed guidelines in 2004, updated in 2017, for indications to order and continue telemetry monitoring in hospitalized patients. The Society of Hospital Medicine’s Choosing Wisely campaign has highlighted the importance of discontinuing telemetry for non-ICU patients. Despite these guidelines, inappropriate telemetry use remains high, with up to 43% of patients on telemetry without a clear indication for use. Over-utilization of this resource can result in unnecessary testing, “alarm fatigue” and increase hospitalization costs. It is important to be familiar with these indications and re-assess needs on a daily basis.

Pearl: Inappropriate telemetry use remains high and is likely to increase cost of care and produce false positives potentially resulting in errors in patient management. Reconsider ordering telemetry in patients without a clear indication and re-assess the need for continued monitoring daily.

AHA NEJM Journal Watch JAMA SHM – Choosing Wisely
Lactated Ringer’s vs Normal Saline

Evidence: According to two single center trials, one looking at patients admitted to the ICU and the other at patients admitted to the floor, administering balanced crystalloids (LR) in the ED may be superior to normal saline, resulting in a 1% lower rate of a composite measure of 30 day all-cause-mortality, new renal-replacement therapy, or persistent renal dysfunction with the benefit driven by kidney injury in floor patients. Normal saline can cause iatrogenic hyperchloremic metabolic acidosis which can lead to renal vasoconstriction, relative hypotension, and relative hyperkalemia. These physiologic realities have now been shown to have clinical consequences.

Pearl: Favor using LR over NS when giving IVF resuscitation to prevent acute kidney injury, particularly when using large volumes, treating severe sepsis, or treating patients with diarrhea.

Oxygen Therapy in the Inpatient Setting

Evidence: There is a common culture among clinicians and nurses to consider supplemental oxygen as beneficial in “sick patients” whose oxygenation saturation is in the normal range. In both human and animal studies, hyperoxia can lead to iatrogenic harm and most importantly, higher oxygen levels have been linked to increased mortality risk. Due to these risks, BMJ recently made oxygen therapy recommendations in acutely ill medical patients. Of note, the benefits or harm of hyperoxia have yet to be established in the setting of cerebral ischemia, out of hospital cardiac arrest, surgical settings and cardiac surgery.

Pearl: In acutely ill medical patients on oxygen therapy, keep peripheral oxygen saturation ≤96%. A target oxygen saturation range of 90-94% appears to be reasonable for most patients. Patients at risk of developing hypercapnic respiratory failure, goal oxygen saturation range is between 88-92%. Patients who have carbon monoxide poisoning, cluster headaches, sickle cell crisis, and pneumothorax, high oxygen saturations approaching 100% are still recommended.

LMWH vs UFH for DVT Prophylaxis in the Hospitalized Patient

Evidence: Multiple studies have evaluated the effectiveness, bleeding risk, and cost/benefits of LMWH vs UFH for DVT prophylaxis

Pearl: Consider LMWH when starting DVT prophylaxis. Avoid LMWH in patients with creatinine clearance < 30 ml/hr. Information on optimal dosing in morbidly obese patients is limited.

Cochrane Library JAMA Lancet Blood Journal Cureus
Sodium Glucose Co-Transporter 2 Inhibitors (SGLT2i) – Benefits and Risks

Evidence: Four major randomized placebo-controlled trials involving thousands of patients followed over several years show that patients on SGLT2i have a lower risk CV events. The most prominent cardiac risk reduction was for hospitalization for heart failure. This drug class also shows secondary benefit in reducing risk for worsening renal function, end stage renal disease or death due to renal disease. However, studies also show an increase incidence of lower limb amputation and DKA associated with SGLT2i. There are four RCTs (phase 3 clinical trials) evaluating SGLT2i in patients with HFpEF and HFrEF without diabetes. Anticipate that SGLT2i may morph into heart failure drugs rather than primary diabetic agents!

Pearl: Greatest CV benefit for SGLT2i is for hospitalization related to heart failure. Be aware of adverse consequences of lower limb amputation and DKA.

Indications for initiation and discontinuation of metformin during medication reconciliation

Evidence: For decades, the FDA recommended against the use of metformin in men and women with a serum creatinine > 1.5 and 1.4 respectively. In 2016, the FDA revised its recommendation and instead of an absolute creatinine cutoff, eGFR is utilized to guide metformin prescribing in patients with mild to moderate renal impairment. Now metformin is contraindicated in patients with eGFR < 30 mL/min/1.73 m2. (See table below for more specific guidelines regarding metformin use)

Pearl: Instead of an absolute creatinine cut off, eGFR should be used to determine the discontinuation or continuation of metformin. In patients with progressive liver disease, decompensated CHF, and alcoholism, metformin should be discontinued.

Glycemic Targets: Standard of Medical Care in Diabetes - 2018

Evidence: The ADA guidelines recommend a Hgb A1c goal 7.0% for most adult patients to reduce the risk of development and progression of microvascular complications. ACP recommends a goal Hgb A1c between 7-8% for most patients with type 2 diabetes. Multiple studies have suggested that there is no significant reduction in cardiovascular disease outcomes and there is an increased risk of severe hypoglycemia in patients with intensive glycemic control who have advanced type 2 diabetes. In patients with limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbidities, a history of severe hypoglycemia, or in patients who it is difficult to achieve target glucose goal despite adequate diabetes education and treatment, less strict hemoglobin A1c goals (< 8%) can be considered.

Pearl: When educating patients and families about blood glucose management based on their A1c, consider an A1c goal (< 8%) for patients with advanced age, more advanced disease and significant comorbidities as risks of strict glycemic control outweighs the benefits.

Creating a culture that applies evidence-based hospitalist medicine to standardize clinical practice amongst the PIMG Hospitalists.

Evidence: The ADA and AACE guidelines for patients with hyperglycemia who require insulin recommend against the prolonged use of SSI as monotherapy and support the use of basal plus correctional insulin with the addition of nutritional insulin for patients with consistent oral intake. In type 2 diabetics, consider insulin based on a total daily dose of 0.4 units/kg for patients presenting with blood sugar levels ≤200 mg/dL and 0.5 units/kg for those with higher initial glucose levels. Half of the total daily dose can be given as basal insulin, and the other half can be divided among meals. Be cautious with insulin dosing in patients aged &gt;70 years, in those with impaired renal function, and in situations in which steroid doses are fluctuating.

Pearl: Stop prolonged SSI monotherapy into a patient’s hospitalization. Instead, consider adding basal and prandial insulin, using a weight-based approach for insulin-naive patients.

Are Follow-Up Blood Cultures Necessary for Gram-Negative Bacteremia?

Evidence: 500 episodes of bacteremia were studied at a tertiary hospital during 2015. 140 patients were found to have Gram-negative rod (GNB) bacteremia. Of these, 52 (37%) had follow up blood cultures which were positive in eight patients (15%), including five with Escherichia coli and one each with K pneumoniae, Serratia marcescens, and Stenotrophomonas maltophilia. The repeat blood culture was more likely to be positive in febrile patients. GNB bacteremia is typically transient and usually resolves rapidly after the initiation of appropriate antibiotic therapy and source control.

Pearl: Follow up blood cultures may be unnecessary for gram negative rod bacteremia unless the patient is febrile.

Infectious Disease Society of America
Effect of Zosyn vs Meropenem on 30-day Mortality for patients with E coli or K pneumoniae blood stream infection

Evidence: A multi-center RCT among patients with ESBL (Ceftriaxone resistant but Zosyn sensitive) E coli or K pneumoniae blood stream infections, definitive treatment with Zosyn compared to Meropenem did not result in a noninferior 30-day mortality.

Pearl: Do NOT use Zosyn for ESBL blood stream infections even if susceptibilities show sensitivity to Zosyn

Journal of the American Medical Association
Antibiotic Therapy for Uncomplicated Gram-Negative Bacteremia

Evidence: A multi-center open labeled RCT showed that patients hospitalized with gram-negative bacteremia achieving clinical stability (afebrile and hemodynamically stable for 48 hours) before day 7, an antibiotic course of 7 days was non-inferior to 14 days. Reducing antibiotic treatment for uncomplicated gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention. This study mainly looked at Enterobacteria from urinary source.

Pearl: You may consider a 7 instead of 14-day course of antibiotics for patients with clinically stable gram-negative bacteremia (think UTI with sepsis).

Infectious Disease Society of America
Oral versus Intravenous Antibiotics for Bone and Joint Infection

Evidence: A UK RTC showed that oral antibiotics were non-inferior to IV antibiotics when used for the first 6 weeks for osteomyelitis and septic arthritis and resulted in similar treatment failure rates at 1 year.

Pearl: You may see ID recommending highly bioavailable oral antibiotics for adherent patients with osteomyelitis or septic arthritis in the future, so hold off on automatically ordering a PICC.

New England Journal of Medicine