News

News

December 3, 2016

Web Edition Now Updated Continually

The Sanford Guide Web Edition was recently updated to a new platform in order to better serve our users. In addition to a clean new theme, the new site also enables us to add new features and functionality for all of our Web Edition and All Access subscribers.
 
The first change that users will notice is that content will no longer be updated on a monthly basis, but will instead be updated continually. This means that as soon as content is edited and reviewed by our editorial board, users will have access to the new information, bringing the latest changes in best practices to our users in real time. As always, our content will remain peer-reviewed by leaders in the field of infectious disease, and will reflect the best available guidance from the literature.
 
Our monthly ID Update newsletter, available on the Web Edition site, the Sanford Guide News site, and through e-mail subscription, will now be published earlier in the month. Updates to our mobile app content will be released according to this new schedule as well.
 
In the coming months, Sanford Guide digital subscribers will notice additional improvements, including a new searchable Spectra of Activity, additional interactive tables, expanded content, and optional add-ons to assist antimicrobial stewardship programs. Contact our sales team for more information about Sanford Guide Digital products and stewardship tools.

November 28, 2016

November ID Update

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Links marked with an asterisk (*) provide details to Sanford Guide Web Edition subscribers, while all other links are universal.

 

New Drug Approval

  • Tenofovir alafenamide (Vemlidy)* has been approved by the FDA for the treatment of chronic hepatitis B in adults with compensated liver disease. The recommended dosage is 25 mg orally once daily with food. Product availability: 25 mg tablets.

 New Dosage Form Approval

  • The FDA has approved Maraviroc(Selzentry) 20 mg/mL oral solution, 25 mg tablets, and 75 mg tabletsThe prescribing information has been updated to include use in pediatric patients 2 years of age and older and weighing at least 10 kg.

New Treatment Guidelines

  •  New clinical practice guidelines for the management of leishmaniasis have been prepared by a panel of the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). The guidelines are available for download on the IDSA website.

Practice Pearls

  • Candida auris, an emerging fungus capable of invasive infection, is associated with high mortality and possible resistance to multiple antifungal drugs. It was first isolated in 2009 from the external ear canal of an inpatient in a Japanese hospital and has since been reported in a number of countries. A recent report describes the first seven US cases of C. auris infection reported to CDC as of August 31. C. auris is a serious concern because accurate laboratory identification requires specialized methods, it tends to be resistant to two or even three antifungal drug classes (azoles, echinocandins, polyenes), and it has caused outbreaks in health care settings. The optimal treatment regimen is not known (MMWR 65:1234, 2016).
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  • Drug interactions that result in prolongation of the QT interval (QT-DDI) are often discovered many years after the drugs are marketed, suggesting the need for a more efficient strategy. A group of investigators recently mined the FDA Adverse Event Reporting System (FAERS) for signals indicating a QT-DDI. They then combined those data with ECGs from their institutional electronic health records (EHR). An unexpected interaction between lansoprazole (a proton-pump inhibitor) and ceftriaxone* was identified. Mean prolongation of the QTc (corrected QT interval) was 12 ms in males and 9 ms in females; men taking the combination were 1.4 times as likely to have a QTc above 500 ms as men taking a single drug. The largest effects were observed in white males and black females. The investigators then used patch-clamp electrophysiology to show that, in combination, the drugs block the hERG channel (the main mechanism by which drugs prolong the QT interval). As a negative control, no evidence of a QT-DDI was identified in the FAERS or EHR data, or in the electrophysiologic experiments, for the combination of lansoprazole and cefuroxime*. Further class analysis found no evidence in the FAERS or EHR for an interaction between any other cephalosporin and proton-pump inhibitor. The mechanism for this intriguing drug interaction, identified using a novel approach of data mining followed by laboratory experimentation, is not known (J Am Coll Cardiol 68:1756, 2016).
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  • Many clinical trials have evaluated the use of cranberry products for UTI prevention, with inconsistent results (often negative, or positive results with flawed methodology). A recent report in JAMA describes a well-designed randomized, double-blind, placebo-controlled trial in elderly female nursing home residents intended to evaluate the effect of cranberry capsules on clinical and microbiologic outcomes. Study participants were administered two oral cranberry capsules (each capsule containing 36 mg of the active ingredient proanthocyanidin) or placebo once a day for a year. There was no significant difference in the primary outcome of bacteriuria plus pyuria, and also no significant differences in any of the secondary outcomes of the study such as symptomatic UTI, rates of death, or hospitalizations. The results of this study are consistent with the view that cranberry products cannot, at this time, be recommended for UTI prevention on the basis of proven benefit (JAMA 316:1879, 2016).
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  • Vancomycin*-induced thrombocytopenia, first described in 1985, is uncommon, poorly characterized, and probably under-diagnosed. The mechanism appears to involve vancomycin-dependent, platelet-reactive antibodies (N Engl J Med 356:904, 2007). A group of researchers conducted a systematic search of the English-language literature using the PubMed, Scopus, and Web of Science databases; 29 case reports, five observational studies, two clinical trials, two letters, and one case series were identified for analysis and the results were recently published. In summary, the precise incidence of vancomycin-induced thrombocytopenia remains unclear. The reaction appears to be duration-dependent with a mean time to platelet nadir of eight days after the first exposure (and significantly shorter in cases of re-exposure). Nadir platelet counts ranged from 2,000 to 100,000 in patients who experienced bleeding. In the case reports, vancomycin-specific antibodies were detected in 13 of 17 patients who were tested. No conclusive association between vancomycin serum concentration and thrombocytopenia was observed. The platelet count returned to normal in a mean time of 5-6 days following discontinuation of vancomycin. Platelet transfusions were used in some patients with variable results; other measures such as corticosteroids, intravenous immunoglobulin, or rituximab were employed in a few patients with unclear benefit (Drug Safety 2016 Nov 15 [Epub ahead of print]).

Drug Shortages (US)

  •  Antimicrobial drugs or vaccines in reduced supply due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list]: Cefoxitin injection, Cefuroxime injection
    • [Continue to be in reduced supply]: Amikacin, Ampicillin injection, Ampicillin/sulbactam, Cefepime, Cefotetan, Ceftazidime, Ceftriaxone, Chloroquine tablets (250, 500 mg), Ciprofloxacin oral suspension, Clindamycin injection, Erythromycin lactobionate injection, Gentamicin injection, Haemophilus B conjugate vaccine, Meningococcal vaccines (various), Mupirocin calcium 2% cream, Ofloxacin 0.3% ophthalmic solution, Oxacillin injection, Penicillin G benzathine, Piperacillin/tazobactam, Poliovirus vaccine inactivated, Tigecycline, Tobramycin, Vancomycin injection, Yellow Fever vaccine
    • [Shortage recently resolved]: DTaP (Daptacel) vaccine, DTaP-IPV/Hib (Pentacel) vaccine, Imipenem-cilastatin injection
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  • Antimicrobial drugs currently unavailable due to manufacturing delays or product discontinuation:
    • [New on the list]: None
    • [Continue to be unavailable]: Cefotaxime injection, Ceftazidime/Avibactam injection, Mupirocin calcium 2% nasal ointment, Penicillin G benzathine/Penicillin G Procaine (Bicillin C-R), Penicillin G procaine injection, Penicillin G benzathine 900,000 units/Penicillin G Procaine 300,000 units (Bicillin C-R 900/300)
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  • Antimicrobial drugs discontinued: Peginterferon alfa-2b (in February 2016; 50 mcg vials still available in limited quantities), Boceprevir (in December 2015), Permethrin 1% topical lotion (in September 2015)
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  • For detailed information including estimated resupply dates, see http://www.ashp.org/menu/DrugShortages
November 23, 2016

Guide to HIV/AIDS Therapy 2016-2017 Release

The Sanford Guide to HIV/AIDS Therapy

 

The Sanford Guide to HIV/AIDS Therapy 2016-2017 print guides are now available! The 24th edition of our Guide to HIV/AIDS Therapy provides practical clinical guidance for the treatment of HIV and AIDS, based on the latest available evidence. Popular with physicians, pharmacists, physician assistants, nurse practitioners, and other clinicians, the Sanford Guide to HIV/AIDS Therapy provides information that is convenient, concise, and reliable.

 

Featuring numerous updates, including the latest generation of combination formulations of ARV drugs and new formulations containing tenofovir alafenamide (TAF), the guide is available in both pocket-size and larger print “library” editions. Sections on differential diagnosis of HIV/AIDS-related clinical syndromes and opportunistic infections, immune reconstitution and treatment of specific OIs have been refined and updated to reflect current trends.

 

Coverage includes:

  • Risk assessment and recommendations for HIV testing
  • Initial evaluation of HIV-infected adults
  • Diagnostic tests
  • Antiretroviral resistance testing
  • Antiretroviral therapy in adults
  • Antiretroviral drugs
  • Pharmacologic features
  • Renal impairment dose adjustments
  • Drug-drug interactions
  • Drugs used for HIV/AIDS-related infections
  • Drug generic and trade names
  • Considerations for HIV-HCV co-infection
  • Opportunistic infections
  • HIV exposure management
  • Immunizations and travel
  • HIV/AIDS in women, newborns, and children
November 11, 2016

Internal Medicine & Critical Care App Release

Lederman Mobile App

The Sanford Guide is excited to announce the release of its newest mobile app, Lederman’s Internal Medicine & Critical Care! Based on the upcoming sixth edition of Lederman’s classic pocketguide, the mobile app features guidance in the treatment of numerous internal medicine scenarios. Developed for use on iPhones, iPads, and Android mobile devices, the app includes the full text of the soon-to-be-released pocketguide, three dozen calculators, bookmarks with user-customized notes, and links to hundreds of external references.

 

Topics covered in the app include code algorithms, renal syndromes, gastroenterology, critical care, toxicology, rheumatology, neurology, cardiology, infectious disease, pulmonary syndromes, endocrinology, hematology, and more.

 

The app is available from the Apple App Store and Google Play.

October 30, 2016

October ID Update

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Links marked with an asterisk (*) provide details to Sanford Guide Web Edition subscribers, while all other links are universal.

 

New Drug Approvals

  • Bezlotoxumab (Zinplava), a human monoclonal antibody that binds to C. difficile toxin B, indicated to reduce recurrence of C. difficile infection (CDI) in patients 18 years of age and older who are receiving antibacterial drugs for CDI and are at high risk for recurrence. Not indicated for treatment of CDI. The recommended dose is a single infusion of 10 mg/kg IV over 60 minutes.
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  • Mebendazole* chewable 500 mg tablets (Vermox Chewable) for the treatment of patients one year of age and older with GI infections caused by Ascaris lumbricoides* (roundworm) and Trichuris trichiura(whipworm). The recommended dosage is one tablet taken as a single dose, chewed completely before swallowing and taken without regard to food intake.

Practice Pearls

  • Clindamycin* is a lincosamide antibiotic that inhibits early stage protein synthesis. It is metabolized to several metabolites that are excreted in feces. In vitro data indicate that the biotransformation of clindamycin is mediated primarily by CYP3A4, and also that the drug is a moderate inhibitor of CYP3A4 (Drug Metab Dispos 31:878, 2003). The degree of inhibition of CYP3A4 is probably insufficient for clindamycin to affect the pharmacokinetics of other drugs, but the data suggest that we should at least be aware of the potential for clindamycin to be affected by strong CYP3A4 inducers or inhibitors. In a recent prospective study, 16 patients with staphylococcal osteoarticular infection treated with oral clindamycin plus rifampin experienced a consistent decrease in clindamycin concentrations compared to control (J Infect 71:200, 2015). These results are consistent with an observational study of 61 patients with gram positive bone and joint infections treated with clindamycin in whom concomitant treatment with rifampin significantly decreased clindamycin trough concentrations (Infection 43:473, 2015), and also with an earlier study of patients treated with continuous infusion clindamycin plus rifampin in whom clindamycin concentrations were reduced (Antimicrob Agents Chemother 54:88, 2010). It is important to note that in these studies there was no clear deleterious impact of lowered clindamycin concentrations on clinical outcome, and also that optimal target concentrations of clindamycin have not been defined (J Infect 72:120, 2016).
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  • Reminder about using fluoroquinolones* in patients with feeding tubes. Administering fluoroquinolones through a feeding tube along with enteral nutrition reduces their bioavailability, presumably due to multivalent cations in the feed such as aluminum, calcium, iron, and magnesium. The extent of the interaction varies among the drugs; ciprofloxacin is affected the most (its bioavailability may be reduced from the usual 70% to about 30-50%), followed by levofloxacin. Moxifloxacin absorption may not be affected at all by enteral feeding. Here are some suggested ways to minimize the fluoroquinolone-enteral feeding interaction:

     

    1) Avoid fluoroquinolone use entirely, or administer intravenously

    2) Hold enteral feeding for 1-2 hours before and 2-4 hours after dosing when using ciprofloxacin or levofloxacin (this may not be necessary for moxifloxacin);

    3) Increase the dose (when using ciprofloxacin) to account for reduced bioavailability.

     

    Fluoroquinolone tablets should be thoroughly crushed and then diluted in 20-60 mL of sterile water before administration through a feeding tube; ciprofloxacin suspension should not be used because it may adhere to the tube and clog it (Am J Health-Syst Pharm 65:2347, 2008).

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  • Can the propylene glycol in intravenous TMP-SMX* cause severe lactic acidosis? A 31-year-old, 106-kg female with pilocytic astrocytoma treated with metronomic temozolomide and steroids was admitted to the ICU for pneumonia and acute respiratory failure requiring mechanical ventilation. Other problems included neurofibromatosis type 1 and hypothyroidism. She was treated initially with cefepime, vancomycin, and azithromycin, and intravenous TMP-SMX 18 mg/kg/day was subsequently added to cover for Pneumocystis jirovecii. Renal and hepatic function were within normal limits. Her respiratory status improved within 36 hours and she was extubated. After three days of TMP-SMX the patient developed a severe metabolic acidosis (pH 7.2, pCO2 19 mm Hg, pO2 107 mm Hg on 2 liters O2, bicarbonate 8 mEq/L, lactate 12.1 mmol/L, anion gap 25 mEq/L). TMP-SMX was discontinued, and within 24 hours the serum bicarbonate increased to 23 and the lactate decreased to 2.9. No cause for lactic acidosis other than TMP-SMX was identified, and the patient’s acid-base status remained normal for the rest of her hospital stay.Propylene glycol is found in many intravenous and oral drugs, including IV TMP-SMX. About half is metabolized in the liver to lactate, pyruvate, and acetate, whereas the other half is excreted unchanged in the urine. Lactic acidosis is a known toxic effect of propylene glycol. Risk factors include renal dysfunction, hepatic dysfunction, and alcoholism, and some authors recommend limiting the intake of propylene glycol to 1 gm/kg/day. TMP-SMX injection contains SMX 80 mg, TMP 16 mg, and propylene glycol 400 mg per mL, and the patient discussed above received 54 gm of propylene glycol per day which, interestingly, is below the recommended daily limit. The only other propylene glycol-containing drug administered to the patient was lorazepam; she received 2 mg, which contributed an additional 0.8 gm. Propylene glycol toxicity has been observed over a wide range of serum concentrations, but unfortunately they were not measured in this patient (Medicine 95:e3478, 2016).
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  • Trimethoprim (TMP) is structurally and pharmacologically related to amiloride, a potassium-sparing diuretic. TMP inhibits the uptake of sodium by epithelial cell sodium channels in the distal tubule, resulting in wasting of sodium, impaired potassium excretion, and metabolic acidosis. Although hyperkalemia is a well-known toxicity of trimethoprim-sulfamethoxazole (TMP-SMX), hyponatremia may be unappreciated. In a recent retrospective cohort study of 76 hospitalized patients who received high-dose TMP-SMX (>8 mg TMP/kg/day) for at least three days, 55 (72.3%) developed hyponatremia (<136 mEq/L) during treatment. Twenty-four of the 55 (43.6%) had a sodium nadir of <130 mEq/L and eight (14.5%) had a nadir of 125 mEq/L or less; the lowest sodium concentration observed was 117 mEq/L. Sodium nadir occurred at a mean time of 5.5 days after initiation of TMP-SMX, and lower sodium concentrations were associated with longer treatment duration and higher cumulative dose of TMP-SMX. Hyponatremia was more likely among African-American patients. Resolution occurred in the majority of patients within three weeks of discontinuation of TMP-SMX (Am J Med 2016 Aug 16 [Epub ahead of print]).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list]: None
    • [Continue to be in reduced supply] Amikacin, Ampicillin injection, Ampicillin/sulbactam, Cefepime, Cefotetan, Ceftazidime, Ceftriaxone, Chloroquine tablets (250, 500 mg), Ciprofloxacin oral suspension, Clindamycin injection, DTaP (Daptacel) vaccine, DTaP-IPV/Hib (Pentacel) vaccine, Erythromycin lactobionate injection, Gentamicin injection, Haemophilus B conjugate vaccine, Imipenem-cilastatin, Meningococcal vaccines (various), Mupirocin calcium 2% cream, Ofloxacin 0.3% ophthalmic solution, Oxacillin injection, Penicillin G benzathine, Penicillin G procaine injection, Piperacillin/tazobactam, Poliovirus vaccine inactivated, Tigecycline, Tobramycin, Vancomycin injection, Yellow Fever vaccine
    • [Shortage recently resolved]: Cefpodoxime 
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  • Antimicrobial drugs currently unavailable due to manufacturing delays or product discontinuation:
    • [New on the list] Penicillin G benzathine 900,000 units/Penicillin G Procaine 300,000 units (Bicillin C-R 900/300)
    • [Continue to be unavailable] Cefotaxime injection, Ceftazidime/Avibactam injection, Mupirocin calcium 2% nasal ointment, Penicillin G benzathine/Penicillin G Procaine (Bicillin C-R)
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  • Antimicrobial drugs discontinued: Peginterferon alfa-2b (in February 2016; 50 mcg vials still available in limited quantities), Boceprevir (in December 2015), Permethrin 1% topical lotion (in September 2015)
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  • For detailed information including estimated resupply dates, see http://www.ashp.org/menu/DrugShortages