Month: July 2016

My elderly patient with aortic stenosis has iron deficiency in the setting of Heyde’s syndrome. Can surgical or transcatheter aortic valve replacement (SAVR, TAVR) reduce her risk of future gastrointestinal bleeding?

FA Manian MD, MPH, , , , , , , , , Leave a comment

Yes! Heyde’s syndrome, characterized by aortic stenosis and GI angiodysplasia1, appears to respond to SAVR or TAVR by reducing future risk of GI bleed.

Cessation of bleeding following SAVR or TAVR with gradual disappearance of angiodysplasia has been reported, in some cases despite long-term anticoagulant therapy. 2,3 In fact, GI bleed may cease in 95% of cases following AVR vs 5% in cases controlled with laparotomy with or without bowel resection.  Further supporting the potential role of valve replacement is the observation that in patients who have undergone SAVR, aortic valve restenosis usually leads to the recurrence of GI bleeding which again resolves after redo surgery.

The pathophysiology of Heyde’s syndrome involves not only increased number of angiodysplasias but higher risk of bleeding from them.  Although its exact  physiological link is unclear, hypo-oxygenation of intestinal mucosa—possibly related to cholesterol emboli with resultant vasodilatation—has been hypothesized, among many others.4   Bleeding from angiodysplasias appears related to the high shear stress across the stenotic aortic valve, leading to acquired von Willebrand’s disease (Type 2AvWF disease) and coagulopathy.4

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References

    1. Heyde EC. Gastrointestinal bleeding in aortic stenosis. N Engl J Med 1958;259:196. https://www.nejm.org/doi/full/10.1056/NEJM200209123471122
    2. Abi-akar R, El-rassi I, Karam N et al. Treatment of Heyde’s syndrome by aortic valve replacement. Curr Cardiol Rev 2011;  7:47–49. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131716/
    3. Pyxaras, SA, Santangelo S. Perkan A et al. Reversal of angiodysplasia-derived anemia after transcatheter aortic valve implantation. J Cardiol Cases 2012; 5: e128–e131. https://www.sciencedirect.com/science/article/pii/S187854091100079X
    4. Kapila A, Chhabra L, Khanna A. Valvular aortic stenosis causing angiodysplasia and acquired von Willebrand’s disease: Heyde’s syndrome. BMJ Case Rep 2014 doi:10.1136/bcr-2013-201890. http://casereports.bmj.com/content/2014/bcr-2013-201890.full.pdf

 

Contributed by Biqi Zhang, Medical Student,  Harvard Medical School

 

My elderly patient with aortic stenosis has iron deficiency in the setting of Heyde’s syndrome. Can surgical or transcatheter aortic valve replacement (SAVR, TAVR) reduce her risk of future gastrointestinal bleeding?

Is aspirin effective in reducing the risk of cancer?

FA Manian MD, MPH, , Leave a comment

Yes, at least for certain types of cancer! A recent report based on 2 ongoing prospective studies (Nurses’ Health Study and Health Professionals Follow-up Study) assessed the risk of cancer in non-regular and regular users of aspirin at a dose of at least 0.5-1.5 standard tablets (325 mg) per week or a low daily dose of 81 mg.  It involved nearly 136,000 subjects while taking into account many potential confounders, including age and cancer screening1.

Compared to non-regular use, aspirin use for at least 6 years was associated with a 3% lower risk of overall cancer, and 15% lower incidence of gastrointestinal cancers, especially colorectal cancers (19% risk reduction); the incidence of breast, advanced prostate or lung cancer was not affected. The irreversible inhibition of cyclooxygenase-2 (COX-2), the principle enzyme that produces pro-inflammatory prostaglandins such as prostaglandin E2 (PGE2) found in human colorectal adenomas and carcinomas2, may explain aspirin’s protective effect1.

 

References

  1. Cao Y, Nishihara R, Wu K, et al. The population impact of long-term use of aspirin and risk of cancer. JAMA Oncol 2016;2:762-769
  2. Greenhough A, Smartt HJM, Moore, et al. The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis 2009;30:377-386.

 

Contributed by Katarzyna Orlewska, Medical Student, Warszawski Uniwersytet Medyczny

Is aspirin effective in reducing the risk of cancer?

My patient is being treated for a urinary tract infection with trimethoprim-sulfamethoxazole (TMP-SMX) and has developed hypoglycemia. Can it be related?

FA Manian MD, MPH1 Comment

Yes! The sulfamethoxazole component of TMP-SMX contains the identical sulfanilamide structural group as sulfonylureas used as oral hypoglycemics1.  It appears to act through mimicking the action of sulfonyureas on the pancreatic islet cells by acting as an insulin secretagogue leading to increased insulin secretion1.   Increased levels of plasma insulin dropping  following interruption of TMP-SMX has been reported,  and is thought to be dose and time dependent1,2.

A major risk factor for this complication is impaired renal function, but poor hepatic function, and concurrent use of drugs that decrease plasma glucose levels have also been implicated (1,2).  Occasionally there are no obvious risk factors.

sulfapiced

 Bonus Pearl: Did you know that sulfonamides were first noted to cause hypoglycemia in 1942, when they were used for treatment of typhoid, paving the way for the development of sulfonylureas as the original oral hypoglycemic agents . The Power of observation strikes again!

References

  1. Forde DG, Aberdein J, Tunbidge A, et al. Hypoglycemia associated with co-trimoxazole use in a 56-year-old caucasian woman with renal impairment. BMJ Case Reports 2012;doi:101136/bcr-2012-007215.
  2. Nunnai G, Celesia BM, Bellissimo F, et al. Trimethoprim-sulfamethoxazole-associated severe hypoglycemia: a sulfonylurea-like effect. Eur Rev Med Pharmacol Sci 2010;14:1015-18.
My patient is being treated for a urinary tract infection with trimethoprim-sulfamethoxazole (TMP-SMX) and has developed hypoglycemia. Can it be related?

How should patients with hospital-associated pneumonia (HAP) be empirically treated under the 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society?

FA Manian MD, MPH, , , , , Leave a comment

Although empiric selection of antibiotics should be based on the local distribution of pathogens associated with HAP and their antimicrobial susceptibilities, routine coverage of Staphylococcus aureus (not necessarily methicillin-resistant S. aureus [MRSA]) and Pseudomonas aeruginosa or other gram-negative bacilli is recommended1.

In patients not at high risk of mortality (including ventilatory support and septic shock) or risk for MRSA (i.e.prior IV antibiotic use within 90 days, hospitalization in a unit where >20% of S. aureus isolates are MRSA or the prevalence of MRSA is unknown), piperacillin-tazobactam, cefepime, levofloxacin, imipenem or meropenem alone is suggested.

In patients not at high risk of mortality but with factors that increase the likelihood of MRSA, piperacillin-tazobactam, cefepime/ceftazidime, ciprofloxacin/levofloxacin, imipenem/meropenem, or aztreonam, plus vancomycin or linezolid should be considered.

In patients at high risk of mortality or receipt of IV antibiotics during the prior 90 days vancomycin or linezolid plus 2 of the following should be used: piperacillin-tazobactam, cefepime/ceftazidime, ciprofloxacin/levofloxacin, imipenem/meropenem, amikacin/gentamicin/tobramycin, or aztreonam are recommended (avoid double β-lactams).

In patients with structural lung disease increasing the risk of gram-negative infections (ie, bronchiectasis or cystic fibrosis), double anti-pseudomonal coverage is recommended.

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Reference

  1. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis, Advance Access published July 14, 2016.https://www.ncbi.nlm.nih.gov/pubmed/27418577  
How should patients with hospital-associated pneumonia (HAP) be empirically treated under the 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society?

What are some of the major changes in the 2016 Infectious Diseases Society of America and the American Thoracic Society guidelines on pneumonia in hospitalized patients?

FA Manian MD, MPH, , , , , , , , , , Leave a comment

The most noticeable change is the elimination of the concept of health-care associated pneumonia (HCAP) altogether1. This action is in part related to the fact that many patients with HCAP were not at high risk for multi-drug resistant organisms (MDROs) , and that individual patient risk factors, not mere exposure to healthcare facilities, were better determinant of  the need for broader spectrum antimicrobials.

Other noteworthy points in the guidelines include:

  • Although hospital-associated pneumonia (HAP) is still defined as a pneumonia not incubating at the time of admission and occurring 48 hrs or more following hospitalization, it now only refers to non-VAP cases; VAP cases are considered a separate category.
  • Emphasis is placed on each hospital generating antibiograms to guide providers with respect to the optimal choice of antibiotics.
  • Despite lack of supportive evidence, the guidelines recommend obtaining respiratory samples for culture in patients with HAP.
  • Prior intravenous antibiotic use within 90 days is cited as the only consistent risk factor for MDROs, including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas sp.

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Reference

  1. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016 ;63:e61-e111.  Advance Access published July 14, 2016. https://www.ncbi.nlm.nih.gov/pubmed/27418577
What are some of the major changes in the 2016 Infectious Diseases Society of America and the American Thoracic Society guidelines on pneumonia in hospitalized patients?

What is the clinical relevance of “SPICE” organisms?

FA Manian MD, MPH, , , , , , , , , , , , , , , , Leave a comment

“SPICE” often stands for the following bacterial species: Serratia spp, Providencia spp, indole-positive Proteae (e.g. Proteus spp. [not mirabilis], Morganella spp., Providencia spp.), Citrobacter spp., and Enterobacter spp.  Some have also included Pseudomonas spp (“P”).

These organisms (as well as Acinetobacter spp., at times “A” in SP”A”CE organisms) often have inducible chromosomal AmpC ß-lactamase genes that may be derepressed during therapy, conferring in vivo ß-lactam resistance despite apparent sensitivity in vitro (1,2). Because AmpC genes in clinical isolates are not routinely screened for in the laboratory, the following treatment approach to these organisms is often adopted (1).

Third generation cephalosporins (e.g. ceftriaxone and ceftazidime) are usually avoided irrespective of in vitro susceptibility. For less serious infections (e.g. urinary tract infections) or severe infections in carefully monitored clinically stable patients, piperacillin-tazobactam and cefepime in particular may be used due to their lower risk of induced resistance. For severe infections (e.g. pneumonia and bacteremia) in seriously ill patients, carbapenems (e.g. meropenem, imipenem-cilastatin) are often the drugs of choice. 

A small retrospective study of patients with infection due to SPICE organisms (about 50% with bacteremia) found cefepime to be as effective as meropenem, but cautioned its use when adequate source control has not been achieved (3). Fluroroquinolones and aminoglycosides may also be considered.

References

  1. MacDougall C. Beyond susceptible and resistant, part I: treatment of infections due to Gram-negative organisms with inducible ß-lactamases. J Pediatr Pharmacol Ther 2011;16:23-30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136230/
  2. Jacoby GA. AmpC ß-lactamases. Clin Microbiol Rev 2009;22:161-182. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2620637/
  3. Tamma PD, Girdwood SCT, Gopaul R, et al. The use of cefepime for treating AmpC ß-lactamase-producing Enterobacteriaceae. Clin Infect Dis 2013;57:781-8. https://academic.oup.com/cid/article/57/6/781/330020

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Contributed in part by Avi Geller, Medical Student, Harvard Medical School, Boston, MA

 

What is the clinical relevance of “SPICE” organisms?

Is clindamycin an acceptable empiric monotherapy for Staphylococcus aureus (SA) infections in adults?

FA Manian MD, MPH, , Leave a comment

Clindamycin is active in-vitro against many strains of SA and is indicated in the treatment of SA mild-to-moderate skin and soft tissue infections (SSTIs), including some methicillin-resistant strains 1,2.  However, evidence for its use as monotherapy against SA infections in other body sites is limited or lacking.   For example, in adults with pneumonia, efficacy of clindamycin is based solely on case series that excluded monotherapy3.  For bone and joint infections, clindamycin has limited evidence of efficacy in adults, and is not recommended in the treatment of endovascular or central nervous system infections2.

 Emergence of resistance to clindamycin in previously susceptible SA isolates may also occur during therapy conferred by erythromycin resistance methylase (erm) gene which is typically screened for by the “D-zone” test2 (Figure).  Increasing resistance of SA to clindamycin has led to recommendation against its empiric use for severe or complicated SSTIs (e.g. large abscess or deep infections)4.  

dzoneclindapcrop

Fig. The “E” disk (on left) contains erythromycin; “CC” disk (on right) contains clindamycin. The test detects inducible clindamycin resistance in erythromycin-resistant , clindamycin- susceptible isolates (http://www.cdc.gov/groupbstrep/images/lab-positivegbs-lg.jpg).

References:

  1. Miller LG, Daum RS, Creech CB, Young D, Downing MD, Eells SJ, Pettibone S, Hoagland RJ, Chambers HF. Clindamycin versus trimethoprim–sulfamethoxazole for uncomplicated skin infections. N Engl J Med 2015;372:1093-103. 
  2. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, Rybak MJ. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011;52:e18-55. 
  3. Lobo LJ, Reed KD, Wunderink RG. Expanded clinical presentation of community-acquired methicillin-resistant Staphylococcus aureus pneumonia. Chest 2010; 138:130-6. 
  4. VanEperen AS, Segreti J. Empirical therapy in Methicillin-resistant Staphylococcus Aureus infections: An Up-To-Date approach. J Infect Chemother 2016;22:351-9.

Contributed by Nathan T. Georgette, 4th year, Harvard Medical School student

 

Is clindamycin an acceptable empiric monotherapy for Staphylococcus aureus (SA) infections in adults?

What is the mechanism of pericardial effusion formation in heart failure?

FA Manian MD, MPH, Leave a comment

Pericardial space contains 15-35 ml of fluid under physiologic conditions (1). Pericardial formation is dependent on the ultrafiltration of plasma across epidcardial and parietal pericardial capillaries a well as interstitial fluid traversing the epicardium, and is removed by the lymphatic system (1). The prevalence of pericardial fluid in congestive heart failure is 12-20%.

Experimental animal data and observations from human studies suggest that pericardial effusion in heart failure only occurs in the setting of high right-sided filling pressures. In a retrospective study of patients with primarily left ventricular dysfunction with or without pericardial effusion, enlarged right ventricular diastolic internal dimension on echocardiography was strongly correlated with the presence of pericardial effusion while systolic and diastolic internal dimensions were not (2).  Thus in patients with heart failure and pericardial effusion, high right-sided filling pressures should be suspected.

 

References

  1. Natanzon A, Kronzon I. Pericardial and pleural effusions in congestive heart failure—anatomical, pathophysiologic, and clinical considerations. Am J Med Sci 2009;338:211-216. https://www.ncbi.nlm.nih.gov/pubmed/19574887
  2. Kessler KM, Rodriguez D, Rahim A, et al. Echocardiographic observations regarding pericardial effusions associated with cardiac disease. Chest 1980;78:736-40. https://www.ncbi.nlm.nih.gov/pubmed/7428456
What is the mechanism of pericardial effusion formation in heart failure?

What is the mechanism of pleural fluid formation in congestive heart failure (CHF)?

FA Manian MD, MPH, , Leave a comment

The pleural fluid in CHF originates from increase filtration of plasma across the capillaries of the visceral pleura and, more importantly, excess fluid in the interstitial spaces of the lung, both related to the increased hydrostatic and capillary wedge pressures (1).

It is postulated that leak of edema fluid into the pleural space may serve as a “safety valve” to mitigate overflooding of alveoli (2). 

Interestingly, although the pleural effusion is commonly bilateral in CHF, when unilateral, it is more likely on the right (1). The reason for this finding is unclear but several hypotheses have been put forth including compression of the azygous vein (which drains a portion of the parietal pleura of right lung) due to the dilatation of the right heart, and compression of the right pulmonary veins by an enlarged right atrium (1).  

Bonus Pearl: A minimum of 50 ml and 200 ml of pleural fluid are required for visibility on lateral and posteroanterior views of a chest radiograph, respectively (3).

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References

  1. Natanzon A, Kronzon I. Pericardial and pleural effusions in congestive heart failure—anatomical, pathophysiologic, and clinical considerations. Am J Med Sci 2009;338:211-216. https://www.ncbi.nlm.nih.gov/pubmed/19574887
  2. Zocchi L. Physiology and pathophysiology of pleural fluid turnover. Eur Respir J 2002;20:1545-1558. http://erj.ersjournals.com/content/20/6/1545.short
  3. Mammarappallil JG, Anderson SA, Danelson KA, et al. Estimation of pleural fluid volumes on chest radiography using computed tomography volumetric analysis: an update of the visual prediction rule. J Thorac Imaging 2015;30:336-339.https://www.ncbi.nlm.nih.gov/pubmed/25811356

 

What is the mechanism of pleural fluid formation in congestive heart failure (CHF)?