My patient with COPD exacerbation on corticosteroids has an elevated white blood cell and neutrophil count. How can I tell if his elevated neutrophil count is caused by the corticosteroids or an acute infection?

The most helpful lab data favoring corticosteroid-induced granulocytosis (CIG) is the absence of a shift to the left in the peripheral WBC (ie, no more than 6% band forms) and toxic granulation.1 Although the total WBC itself is less helpful, experimental studies have reported a mean maximum neutrophil counts 2.4 times the base line after IV injection of hydrocortisone (200 mg) 2, and a mean increase of 4,000 neutrophils/mm3 after prednisone (20-80 mg). 3

Several possible mechanisms for CIG revolving around altered neutrophil characteristics and dynamics have been proposed4, including

  • Reduced egress from blood into tissues
  • Demargination from vascular endothelial surfaces
  • Delayed apoptosis
  • Enhanced release from the bone marrow.

An experimental animal study reported that only 10% of CIG is related to bone marrow release of neutrophils with the rest related to demargination (61%) and reduced egress from blood or delayed apoptosis (29%).4 This study may explain why high percentage of band forms would not be expected CIG.

References

  1. Shoenfeld Y, Gurewich Y, Gallant LA, et al. Prednisone-induced leukocytosis: influence of dosage, method, and duration of administration on the degree of leukocytosis. Am J Med 1981;71:773-78. Link
  2. Bishop CR, Athens JW, Boggs DR, et al. Leukokinetic studies: A non-steady-state kinetic evaluation of the mechanism of cortisone-induced granulocytosis. J Clin Invest 1986;47:249-60. https://www.ncbi.nlm.nih.gov/pubmed/5638121
  3. Dale DC, Fauci AS, Guerry DuPont, et al. Comparison of agents producing a neutrophilic leukocytosis in man. J Clin Invest 1975;56:808-13. PDF
  4. Nakagawa M, Terashma T, D’yachkova YD, et al. Glucocorticoid-induced granulocytosis: Contribution of marrow release and demargination of intravascular granulocytes. Circulation 1998;98:2307-13. PDF

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My patient with COPD exacerbation on corticosteroids has an elevated white blood cell and neutrophil count. How can I tell if his elevated neutrophil count is caused by the corticosteroids or an acute infection?

Can native valve infective endocarditis be associated with hemolytic anemia?

Yes, but it’s rare!  Hemolytic anemia (HA) in the setting of infective endocarditis (IE) has only been described in a few case reports (1-3).  Although diseased valves may cause shearing stress that fragments RBCs, similar to that associated with mechanical heart valves, an autoimmune hemolytic process has also been implicated. 

A 2018 case report describes a patient with hypertrophic obstructive cardiomyopathy (HOCM) with left ventricular outflow tract (LVOT) obstruction who had HA secondary to subacute IE due to Actinomyces israelii (1).   The anemia completely resolved after treating the IE (1). The cause was most likely mechanical shearing (schistocytes or fragmented RBCs present on peripheral smear) by the diseased valves; autoimmune hemolysis was considered unlikely in this case due to consistently negative Coombs tests and failure to respond to corticosteroids (1). 

An autoimmune mechanism was invoked by a 1999 report reviewing 6 cases of HA associated with IE (3).  All patients had fragmented erythrocytes, but several also demonstrated an immune-mediated mechanism for their HA, supported by the presence of spherocytes, splenomegaly, and + Coombs test (2,3).  The production of anti-erythrocyte antibodies, modification of antigenicity of erythrocyte antigens, or unmasking of antigens in IE may play a role (1,3). Additional evidence in support of an immune-mediated mechanism of HA in IE has been provided by an experimental study demonstrating significantly shorter RBC half-life in rabbits with intact spleen compared to that of splenectomized animals (4).

 

References

1. Toom S, Xu Y. Hemolytic anemia due to native valve subacute endocarditis with Actinomyces israellii infection. Clin Case Rep 2018;6: 376-79. https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccr3.1333 

2. Hsu CM, Lee PI, Chen JM, et al. Fatal Fusarium endocarditis complicated by hemolytic anemia and thrombocytopenia in an infant. Pediatr Infect Dis 1994;13:1146-48. https://www.ncbi.nlm.nih.gov/pubmed/7892087 

3. Huang HL, Lin FC, Hung KC, et al. Hemolytic anemia in native valve infective endocarditis. Jpn Circ J 1999;63:400-403. https://www.ncbi.nlm.nih.gov/pubmed/10943622 

4. Joyce RA, Sand MA. Mechanism of anaemia in experimental bacterial endocarditis. Scand J Haematol 1975;15:306-11. https://www.ncbi.nlm.nih.gov/pubmed/1198067 

 

Contributed by Scott Goodwin, Medical Student, Harvard Medical School, Boston, MA. 

 

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Can native valve infective endocarditis be associated with hemolytic anemia?

How can I tell if my febrile patient who uses IV drugs had cotton fever?

Although IV drug use (IVDU) is associated with febrile illness of numerous etiologies (eg, soft tissue infections, pneumonia, bacteremia, endocarditis), certain features of a febrile illness may be helpful in considering cotton fever (CF) as the cause.1-3

First, onset of fever—often associated with chills, shortness of breath, nausea, vomiting, headache, abdominal pain and myalgias—in CF is usually manifest within 10-30 minutes of drug injection. Second, infectious disease workup, including blood cultures and chest radiograph, are unrevealing despite clinical signs of systemic inflammatory response syndrome (SIRS), such as leukocytosis, tachypnea and tachycardia. Third, symptoms and clinical signs of inflammation usually resolve or improve within 6-12 h of onset (less commonly up to 24-48 h). Nevertheless, CF remains a diagnosis of exclusion.

As for the cause of CF, the most widely-held theory revolves around the endotoxin of Pentoea agglomerans (formerly Enterobacter agglomerans), a gram-negative rod that colonizes cotton plants. Since cotton is often used as a filter during injection of illicit substances, any endotoxin present in the cotton is also injected resulting in abrupt onset of a febrile illness. Of note, the toxin is water soluble and heating (often part of the preparation of the drug) enhances its toxic effect.3

References

  1. Zerr AM, Ku K, Kara A. Cotton Fever: a condition self-diagnosed by IV drug users. JABFM 2016;29: 276-279.PDF
  2. Xie Y, Pope BA, Hunter AJ. Cotton fever: does the patient know best? J Gen Intern Med 31:442-4. PDF
  3. Torka P, Gill S. Cotton fever: an evanescent process mimicking sepsis in an intravenous drug abuser. J Emerg Med 2013;44:e385-e387. PDF
How can I tell if my febrile patient who uses IV drugs had cotton fever?

Why has my patient with Clostridium difficile diarrhea developed Klebsiella bacteremia?

Although there are many potential sources for Klebsiella sp. bacteremia, C. difficile infection (CDI) itself may be associated with GI translocation of enteric organisms.

A retrospective study of over 1300 patients found an incidence of 1.8% for CDI-associated bacteremia. E. coli, Klebsiella sp. , or Enterococcus sp. accounted for 72% of cases. History of malignancy, neutropenia (at the time of CDAD), and younger age (mean 59 y) were among the risk factors.1 Another study reported over 20 cases of bacteremia caused by C. difficile plus other bacteria often of enteric origin such the aforementioned organisms, Bacteroides sp, Candida sp, and Enterobacter sp.2

CDI is thought to predispose to bacterial translocation through the GI tract by alteration of mucosal indigenous microflora, overgrowth of certain pathogens, and presence of inflammation in the mucosa.3 Interestingly, C. difficile toxin A or B may play an active role in the bacterial adherence and penetration of the intestinal epithelial barrier.4  

Bonus pearl: Did you know that C. difficile may be found in the normal intestinal flora of 3% of healthy adults, 15-30% of hospitalized patients, and up to 50% of neonates? Why neonates seem immune to CDI is another fascinating story!

 

References

  1. Censullo A, Grein J, Madhusudhan M, et al. Bacteremia associated with Clostridium difficile colitis: incidence, risk factors, and outcomes. Open Forum Infectious Diseases, Volume 2, Issue suppl_1, 1 December 2015, 943, https://doi.org/10.1093/ofid/ofv133.659 https://academic.oup.com/ofid/article/2/suppl_1/943/2635179
  2. Kazanji N, Gjeorgjievski M, Yadav S, et al. Monomicrobial vs polymicrobial Clostridum difficile bacteremia: A case report and review of the literature. Am J Med 2015;128:e19-e26. https://www.amjmed.com/article/S0002-9343(15)00458-1/abstract
  3. Naaber P, Mikelsaar RH, Salminen S, et al. Bacterial translocation, intestinal microflora and morphological changes of intestinal mucosa in experimental models of Clostridium difficile infection. J Med Microbiol 1998; 47: 591-8. https://www.ncbi.nlm.nih.gov/pubmed/9839563 
  4. Clostridium difficile toxins may augment bacterial penetration of intestinal epithelium. Arch Surg 1999;134: 1235-1242. https://jamanetwork.com/journals/jamasurgery/fullarticle/390434
Why has my patient with Clostridium difficile diarrhea developed Klebsiella bacteremia?

Should Aerococcus urinae growth from the urine of my elderly patient be considered a pathogen?

Although for many years Aerococcus urinae was considered a urinary contaminant, increasingly it is recognized as an emerging pathogen capable of causing not only urinary tract infection (UTI) but also secondary bacteremia and endocarditis, among others.1   

The proportion of patients with aerococcal bacteriuria with symptoms suggestive of UTI ranges from 55-98%.1 So A. urinae can no longer be assumed to be a contaminant, particularly in the presence of symptoms suggestive of UTI.

A. urinae UTI often affects the elderly (median age 79 y) and those with pre-existing urinary tract pathologies, such as prostatic hyperplasia, urethral stricture, renal calculi, and prior urinary tract surgery.2,3 Many patients also have underlying comorbidities such as diabetes, heart disease, dementia, and chronic renal failure.3

One clue to the presence of A. urinae in the urine is its particularly pungent odor reminiscent of that of patients with trimethylaminuria (fish odor syndrome).4

Once you decide you should treat A. urinae, keep in mind that it is NOT predictably susceptible to trimethoprim-sulfamethoxazole, fluoroquinolones, or fosfomycin!  Instead, consider penicillin, ampicillin, cephalosporin, or nitrofurantoin to which most strains are susceptible.5,6.

 

References

  1. Rasmussen M. Aerococcus: an increasingly acknowledged human pathogen. Clin Microbiol Infect 2016;22:22-27. https://www.ncbi.nlm.nih.gov/pubmed/26454061
  2. Tathireddy H, Settypalli S, Farrell JJ. A rare case of aerococcus urinae infective endocarditis. J Community Hosp Intern Med Perspectives 2017; 7:126-129. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473194/
  3. Higgins A, Garg T. Aerococcus urinae: An emerging cause of urinary tract infection in older adults with multimordidity and urologic cancer. Urology Case Reports 2017;24-25. https://www.ncbi.nlm.nih.gov/pubmed/28435789
  4. Lenherr N, Berndt A, Ritz N, et al. Aerococcus urinae: a possible reason for malodorus urine in otherwise healthy children. Eur J Pediatr. 2014;173:1115-7 https://www.ncbi.nlm.nih.gov/pubmed/24913181
  5. Christensen JJ, Nielsen XC. Aerococcus urinae. Antimicrobe @ http://www.antimicrobe.orgb75.asp , accessed June 14, 2018.
  6. Dimitriadi D, Charitidou C, Pittaras T, et al. A case of urinary tract infection caused by Aerococcus urinae. J Bacteriol Mycol 2016; 2: 00041. https://pdfs.semanticscholar.org/a1cf/048d8444ce054ca9a332f7c2b4a218325ff6.pdf

 

Should Aerococcus urinae growth from the urine of my elderly patient be considered a pathogen?

Should I be concerned about the umbilical hernia in my patient with cirrhosis and ascites?

Although umbilical hernia in patients with cirrhosis and ascites is common and often “expected” (a rate of 20% during the course of their disease), it can be associated with significant risk of complications such as incarceration, ascites drainage, peritonitis, and spontaneous rupture or evisceration from necrosis of overlying skin.1,2

A 2007 retrospective study involving patients with cirrhosis and umbilical hernia reported a complication rate of 77% and related mortality of 15% among those managed conservatively (mean period of observation ~ 5 years); MELD score could not predict failure of conservative management (median 22 in complicated vs 24 in uncomplicated).3

Because the risk of death with hernia repair in urgent settings is 7x higher than for elective hernia repair in cirrhotic patients, there has been increasing interest in elective repair in patients with well-compensated cirrhosis.3 Interestingly, the reported surgical complication rates among patients with well-compensated cirrhosis appear similar to those in noncirrhotic patients.3 If the patient is expected to undergo liver transplantation in the near future, elective hernia repair can be postponed and managed concomitantly.

Bonus pearl: Did you know that spontaneous umbilical hernia rupture is also known as “Flood syndrome” (should be easy to remember!), first described by Frank B Flood, a surgical resident back in 1961? 4

References

  1. Marsman HA, Heisterkamp J, Halm JA, et al. Management in patients with liver cirrhosis and an umbilical hernia. Surgery 2007;142:372-5. https://www.ncbi.nlm.nih.gov/pubmed/17723889
  2. Coelho, JCU, Claus CMP, Campos ACL, et al. Umbilical hernia in patients with liver cirrhosis: a surgical challenge. World J Gastrointest Surg 2016;8:476-82. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942747/
  3. Martens P, Laleman W. Umbilical hernia in a patient with cirrhosis. Cleveland Clin J Med 2015;82: 404-5. https://www.mdedge.com/ccjm/article/100682/hepatology/umbilical-hernia-patient-cirrhosis
  4. Nguyen ET, Tudtud-Hans LA. Flood syndrome: spontaneous umbilical hernia rupture leaking ascitic fluid-a case report. Perm J 2017;21:16-152. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499604/ 

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Should I be concerned about the umbilical hernia in my patient with cirrhosis and ascites?

How should I interpret the growth of “normal respiratory flora” from sputum of my patient with community-acquired pneumonia (CAP)?

Since the primary reason for obtaining a sputum culture in a patient with pneumonia is to sample the lower respiratory tract, you should first verify that the sputum was “adequate” by reviewing the gram stain. Absence of neutrophils (unless the patient is neutropenic) with or without epithelial cells on gram stain of sputum suggests that it may not be an adequate sample (ie, likely saliva)1, and therefore growth of normal respiratory flora (NRF) should not be surprising in this setting.  

Other potential explanations for NRF on sputum culture in patients with CAP include:2-5

  • Delay in sputum processing with possible overgrowth of oropharyngeal flora.
  • Pneumonia caused by pathogens that do not grow on standard sputum culture media (eg, atypical organisms, viruses, anaerobes).
  • Pneumonia caused by potential pathogens such as as Streptococcus mitis and Streptococcus anginosus group that may be part of the NRF.
  • Initiation of antibiotics prior to cultures (eg, in pneumococcal pneumonia).

Of note, since 2010, several studies have shown that over 50% of patients with CAP do not have an identifiable cause.3 So, growing NRF from sputum of patients with CAP appears to be common.

References

  1. Wong LK, Barry AL, Horgan SM. Comparison of six different criteria for judging the acceptability of sputum specimens. J Clin Microbiol 1982;16:627-631. https://www.ncbi.nlm.nih.gov/pubmed/7153311
  2. Donowitz GR. Acute pneumonia. In Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases (2010). Churchill Livingstone, pp 891-916.
  3. Musher DM, Abers MS, Bartlett JG. Evolving understanding of the causes of pneumonia in adults, with special attention to the role of pneumococcus. Clin Infect Dis 2017;65: 1736-44. https://www.ncbi.nlm.nih.gov/pubmed/29028977
  4. Abers MS, Musher DM. The yield of sputum culture in bacteremic pneumococcal pneumonia after initiation of antibiotics. Clin Infect Dis 2014; 58:1782. https://www.ncbi.nlm.nih.gov/pubmed/24604901
  5. Bartlett JG, Gorbach SL, Finegold SM. The bacteriology of aspiration pneumonia. Bartlett JG, Gorbach SL, Finegold SM. Am J Med 1974;56:202-7. https://www.ncbi.nlm.nih.gov/pubmed/4812076
How should I interpret the growth of “normal respiratory flora” from sputum of my patient with community-acquired pneumonia (CAP)?