Streptococcus pneumoniae

My patient with acute onset headache, photophobia, and neck stiffness does not have CSF pleocytosis. Could she still have meningitis?

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

Although the clinical diagnosis of meningitis is often supported by the presence of abnormal number of WBCs in the CSF (AKA pleocytosis), meningitis may be present despite its absence.

Among viral causes of meningitis in adults, enteroviruses are associated with lower CSF WBC count compared to herpes simplex and varicella zoster, with some patients (~10%) having 0-2 WBC’s/mm31,2.  Of interest, among children, parechovirus (formerly echovirus 22 and 23) meningitis is characterized by normal CSF findings3.

Though uncommon, bacterial meningitis without CSF pleocytosis has been reported among non-neutropenic adults,  including Neisseria meningitidis, Streptococcus pneumoniae, Hemophilus influenzae, Listeria monocytogenes, E. coli, and Proteus mirabilis4.  A European study also reported normal CSF WBC in nearly 10% of patients with Lyme neuroborreliosis (including meningitis) caused primarily by Borrelia garinii5.

Cryptococcal meninigitis may also be associated with normal CSF profile in 25% of patients with HIV infection6.

 

References

  1. Ihekwaba UK, Kudesia G, McKendrick MW. Clinical features of viral meningitis in adult:significant differences in cerebrospinal fluid findings among herpes simplex virus, varicella zoster virus, and enterovirus infections. Clin Infect Dis 2008;47:783-9. https://www.ncbi.nlm.nih.gov/pubmed/18680414
  2. Dawood N, Desjobert E, Lumley J et al. Confirmed viral meningitis with normal CSF findings. BMJ Case Rep 2014. Doi:10.1136/bcr-2014-203733. http://casereports.bmj.com/content/2014/bcr-2014-203733.abstract
  3. Wolthers KC, Benschop KSM, Schinkel J, et al. Human parechovirus as an important viral cause of sepsis like illness and meningitis in young children. Clin Infect Dis 2008;47:358-63. https://www.ncbi.nlm.nih.gov/pubmed/18558876
  4. Hase R, Hosokawa N, Yaegashi M, et al. Bacterial meningitis in the absence of cerebrospinal fluid pleocytosis: A case report and review of the literature. Can J Infect Dis Med Microbiol 2014;25:249:51. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211346/pdf/idmm-25-249.pdf
  5. Ogrinc K, Lotric-Furlan S, Maraspin  V, et al. Suspected early Lyme neuroborreliosis in patients with erythema migrans. Clin Infect Dis 2013; 57:501-9. https://www.ncbi.nlm.nih.gov/pubmed?term=23667259
  6. Darras-Joly C, Chevret S, Wolff M, et al. Cryptococcus neoformans infection in France: epidemiologic features of and early prognostic parameters for 76 patients who were infected with human immunodeficiency virus. Clin Infect Dis 1996;23:369-76. https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cid/23/2/10.1093/clinids/23.2.369/2/23-2-369.pdf?Expires=1501035620&Signature=FhHMHUHAMmT3rz4ld8QAMet-weu-BWgm5YR6nA4jjSGVGIeaVlMNPgeOkW2fniiel54HQhIs1Kkp3PpzT1glxhJeZvQiGXQCSOoF-jS1SK7S~kBb-oHs4qsIJzN0OJxNAXfoJi4bl7OeKaLTyIE3P8~slwH0BBi7RncSYVgVR4NkOnFpYgn27~wY7pDSUNWvzGFKoSeYGeM0TsAqna-QmXzodITB5bgr1mO6Q6OGUxCsqRwhr6xNb~4G93oqRcsO19gyUluCE0xYt0KbKWuQxJeh8AbtJkNrS08~XInMR50bQZOUb80j0~dtg9jRTGzXQaDllVByoX2Alr48hlhogw__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q
My patient with acute onset headache, photophobia, and neck stiffness does not have CSF pleocytosis. Could she still have meningitis?

Is treatment of pneumococcal pneumonia with bacteremia any different than pneumococcal pneumonia without bacteremia?

FA Manian MD, MPH, , , Leave a comment

In the absence of disseminated infection such as meningitis or endocarditis, there is no convincing evidence that bacteremic pneumococcal pneumonia (BPP) requires either longer course of IV or oral antibiotics.

In fact, although previously thought to have a worse prognosis, recent data have failed to demonstrate any difference in time to clinical stability, duration of hospital stay or community-associated pneumonia (CAP)-related mortality with BPP when other factors such as patient comorbidities and severity of disease are also considered1,2. 

Although many patients with CAP receive 7-10 days of antibiotic therapy, shorter durations as little as 5 days may also be effective3,4.  Generally, once patients with BPP have stabilized on parenteral therapy, a switch to an appropriate oral antibiotic (eg, a β-lactam or a respiratory quinolone such as levofloxacin) can be made safely5. 

Although large randomized-controlled studies of treatment of BPP are not available, a cumulative clinical trial experience with levofloxacin for patients with BPP reported a successful clinical response in >90% of patients (median duration of therapy 14 d)6. Resistance to levofloxacin and failure of treatment in pneumococcal pneumonia (with or without bacteremia), however, has been rarely reported7.

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References

  1. Bordon J, Peyrani P, Brock GN. The presence of pneumococcal bacteremia does not influence clinical outcomes in patients with community-acquired pneumonia. Chest 2008;133;618-624.
  2. Cilloniz C, Torres A. Understanding mortality in bacteremic pneumococcal pneumonia. J Bras Pneumol 2012;38:419-421.
  3. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44:S27-72.
  4. Shorr F, Khashab MM, Xiang JX, et al. Levofloxacin 750-mg for 5 days for the treatment of hospitalized Fine Risk Class III/IV community-acquired pneumonia patients. Resp Med 2006;100:2129-36.
  5. Ramirez JA, Bordon J. Early switch from intravenous to oral antibiotics in hospitalized patients with bacteremic community-acquired Streptococcus pneumonia pneumonia. Arch Intern Med 2001;161:848-50.
  6. Kahn JB, Bahal N, Wiesinger BA, et al. Cumulative clinical trial experience with levofloxacin for patients with community-acquired pneumonia-associated pneumococcal bacteremia. Clin Infect Dis 2004;38(supp 1):S34-42.
  7. Davidson R, Cavalcanti R, Brunton JL, et al. Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N Engl J Med 2002;346:747-50.
Is treatment of pneumococcal pneumonia with bacteremia any different than pneumococcal pneumonia without bacteremia?

When should I pay attention to the minimum inhibitory concentration (MIC) of an antibiotic despite the lab reporting it to be in the “Susceptible” range?

FA Manian MD, MPH, , , , , , , , 1 Comment

In most situations, you will most likely choose an antibiotic based on the laboratory reporting of “Susceptible” (vs “Resistant”), not the actual MIC value of the drug and that’s fine.  

However, there may be a few instances when you may need to pay more attention to the actual MICs. Many experts recommend caution when “high” MICs within a susceptible range are observed in the following situations:   

  1. Vancomycin MIC >1 ug/ml in Staphylococcal aureus (methicillin-sensitive or –resistant) infections because of its possible association with clinical failure and, at times, increased mortality1,2.
  2. Ciprofloxacin or levofloxacin MIC>0.25 ug/ml in bacteremia caused by Gram-negative bacilli (including Enterobacteriacae as well as Pseudomonas aeruginosa) because of its association with an adverse outcome (eg, longer average hospital stay post-culture and duration of infection) but not necessarily mortality3-5.
  3. Levofloxacin MIC ≥ 1.0 ug/ml in Streptococcus pneumoniae infections, because of its association with an adverse clinical outcome based on drug pharmacodynamics and anecdotal reports of treatment failure6,7.

 

References

  1. Jacob JT, DiazGranados CA. High vancomycin minimum inhibitory concentration and clinical outomces in adults with methicillin-resistant Staphylococcus aureus infections: a meta-analysis. Int J Infect Dis 2013;17:e93-e100.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780595/
  2. Kalil AC, Van Schooneveld TC, Fey PD, et al. Association between vancomycin minimum inhibitory concentration and mortality among patients with Staphylococcus aureus bloodstream infections: A systematic review and meta-analysis. JAMA 2014;312:1552-1564. https://www.ncbi.nlm.nih.gov/pubmed/25321910
  3. DeFife R, Scheetz MH, Feinglass J, et al. Effect of differences in MIC values on clinical outcomes in patients with bloodstream infections caused by Gram-negative organisms treated with levofloxacin. Antimicrob Agents Chemother 2009;53:1074-79. http://aac.asm.org/content/53/3/1074.full
  4. Falagas ME, Tansarli GS, Rafailidis PI, et al. Impact of antibiotic MIC on infection outcome in patients with susceptible Gram-negative bacteria a systematic review and meta-analysis. Antimicrob Agents Chemother 2012;56:4214-22. https://www.ncbi.nlm.nih.gov/pubmed/22615292
  5. Zelenitsky SA, Harding GKM, Sun S, et al. Treatment and outcome of Pseudomonas aeruginosa bacteremia: an antibiotic pharmacodynamics analysis. J Antimicrob Chemother 2003;52:668-674. https://www.ncbi.nlm.nih.gov/pubmed/12951354
  6. Davidson R, Cavalcanti R, Brunton JL, et al. Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N Engl J Med 2002;346:. 2002;346:747-50. https://www.ncbi.nlm.nih.gov/pubmed/11882730
  7. De Cueto M, Rodriguez JM, Soriano MJ, et al. Fatal levofloxacin failure in treatment of a bacteremic patient infected with Streptococcus pneumoniae with a preexisting parC mutation. J Clin Microbiol 2008;46:1558-1560.  http://jcm.asm.org/content/46/4/1558.full

Contributed in part by Nick Van Hise, Pharm.D., BCPS, Infectious Diseases Clinical Pharmacist, Edward-Elmhurst Hospitals, Naperville, Illinois.

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When should I pay attention to the minimum inhibitory concentration (MIC) of an antibiotic despite the lab reporting it to be in the “Susceptible” range?

What is the significance of Howell-Jolly bodies in the peripheral smear of my patient with a spleen who presents with pneumonia?

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

Howell-Jolly bodies (HJBs, Figure) are often indicative of asplenia (either post-splenectomy or congenital absence) or hyposplenism associated with a variety of conditions, including  sickle cell disease, autoimmune disorders, celiac disease, inflammatory bowel disease (particularly ulcerative colitis), HIV, cirrhosis, primary pulmonary hypertension, splenic irradiation, amyloidosis, sarcoidosis, bone marrow transplantation, and high-dose corticosteroid therapy1-4.

Patients with pneumonia and HJBs on peripheral smear may be hyposplenic and at risk of potentially serious infections, predominantly caused by encapsulated bacteria eg, Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis3.  Such patients should be immunized against these organisms, including sequential receipt of both conjugated and polysaccharide pneumococcal vaccines3,5.

HJBs are nuclear remnants in circulating mature red blood cells which are usually pitted by the spleen under normal physiological conditions. 

Final Fun Pearl:  Did you know that  HJBs were named after Henry Howell, an American physiologist who pioneered the use of heparin as an anti-coagulant and Justin Jolly, a French hematologist who was among the first to film mitotic activity in cells?

howelljollymgh

Figure. Howell-Jolly body in an RBC. Photo courtesy of Michael S. Abers, MD

Contributed by Katarzyna Orlewska, Medical Student, Warszawski Uniwersytet Medyczny, Poland

 

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References

  1. Di Sabatino, A, Carsetti R, Corazza G. Post-splenectomy and hyposplenic states. Lancet 2011;378:86–97. https://www.ncbi.nlm.nih.gov/pubmed/21474172
  2. Brousse, V, Buffet P, Rees D. The spleen and sickle cell disease: the sick(led) spleen. Br J Haematol 2014;166: 165–176. https://www.ncbi.nlm.nih.gov/pubmed/24862308
  3. Mathew H, Dittus C, Malek A, Negroiu A. Howell-Jolly bodies on peripheral smear leading to the diagnosis of congenital hyposplenism in a patient with septic shock. Clin Case Rep 2015;3:714-717. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551333
  4. Ryan FP, Smart RC, Holdsworth CD, et al. Hyposplenism in inflammatory bowel disease 1978;19:50-55. https://www.ncbi.nlm.nih.gov/pubmed/624506
  5. Kuchar E, Miśkiewicz K , Karlikowska M. A review of guidance on immunization in persons with defective or deficient splenic function. Br J Haematol 2015; 171:683-94.  http://onlinelibrary.wiley.com/doi/10.1111/bjh.13660/full

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What is the significance of Howell-Jolly bodies in the peripheral smear of my patient with a spleen who presents with pneumonia?

Is cefpodoxime an appropriate oral antibiotic substitute for ceftriaxone when treating patients with respiratory tract infections caused by penicillin-resistant Streptococcus pneumoniae (PRSP)?

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

Short answer: No!

Although cefpodoxime is also a 3rd generation cephalosporin, its invitro activity against PRSP is not comparable to that of ceftriaxone.  In a study of 21,605 strains of S. pneumoniae collected internationally, whereas 89.1% of PRSP isolates were susceptible to ceftriaxone, only 35% were susceptible to cefpodoxime (1).  Among isolates resistant to penicillin and erythromycin, the susceptibility to ceftriaxone was 86.9% compared to that of 22.7% for cefpodoxime.

This information is important since 32%, and 17.6% of all S. pneumoniae isolates tested in this study  were either penicillin-resistant or penicillin- and erythromycin-resistant, respectively.  

So, when it comes to the coverage of PRSP, there is no oral cephalosporin “equivalent” to ceftriaxone and that includes cefpodoxime.  In fact, the package insert of cefpodoxime states that cefpodoxime is active against S. pneumoniae “excluding penicillin-resistant strains” (2).

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References

  1. Pottumarthy S. Fritsche TR, Jones RN. Comparative activity of oral and parenteral cephalosporins tested against multidrug-resistant Streptococcus pneumonia: report from SENTRY Antimicrobial Surveillance Program (1997-2003). Diag Microbiol Infect Dis 2005;51:147-150. https://www.sciencedirect.com/science/article/pii/S0732889304002081    
  2. http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/050674s014,050675s017lbl.pdf; accessed June 20, 2016.
Is cefpodoxime an appropriate oral antibiotic substitute for ceftriaxone when treating patients with respiratory tract infections caused by penicillin-resistant Streptococcus pneumoniae (PRSP)?

My 65 year old patient has had several bouts of bacterial pneumonia in the past 2 years. Her total serum immunoglobulins are within normal range. Could she still be immunodeficient?

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

Absolutely! Besides HIV infection which should be excluded in all patients with recurrent bouts of bacterial pneumonia irrespective of age, “selective polysaccharide antibody deficiency”, also known as “specific antibody deficiency” or SAD, should also be excluded (1-3). SAD in adults with recurrent pneumonia is not rare, having been reported in about ~8% of such patients (4).  

Think of SAD when your adult patient presents with recurrent bouts of bacterial pneumonia  despite having normal serum total immunoglobulin (IgG, IgA, and IgM) levels and IgG subtypes (1-3).  These patients have a normal response to tetanus toxoid (a protein) but cannot mount adequate antibody response against polysaccharide antigens of pathogens such as pneumococcus.  

One way to diagnose SAD in a suspected patient is through vaccination with 23-valent pneumococcal polysaccharide vaccine (PPSV23).  In patients with low baseline antibody titers to many of the capsular types of pneumococcus included in the PPSV23,  a suboptimal response (defined by the lab) 4 weeks after vaccination with PPSV23 is suggestive of SAD. Remember that if your patient has already been vaccinated with the 13 valent pneumococcal conjugate vaccine (PCV13), you can only evaluate for the response to serotypes included in the  PPSV23 only.

Although there are no randomized-controlled studies and treatment should be individualized, immunoglobulin replacement may reduce the risk of future bouts of pneumonia in SAD (2-3). 

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References

1. Cohn JA, Skorpinski E, Cohn JR. Prevention of pneumococcal infection in a patient with normal immunoglobulin levels but impaired polysaccharide antibody production. Ann Allergy Asthma Immunol 2006;97:603-5. https://www.ncbi.nlm.nih.gov/pubmed/17165266

2. Cheng YK, Kecker PA, O’Byrne MM, Weiler CR. Clinical and laboratory characteristics of 75 patients with specific polysaccharide antibody deficiency syndrome. Ann Alergy Asthma Immunol 2006;97:306-311. https://www.ncbi.nlm.nih.gov/pubmed/17042135

3. Perez E, Bonilla FA, Orange JS, et al. Specific antibody deficiency: controversies in diagnosis and management. Front Immunol 207;8:586. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439175/pdf/fimmu-08-00586.pdf

4. Ekdahl K, Braconier JH, Svanborg C. Immunoglobulin deficiencies and impaired immune response to polysaccharide antigens in adult patients with recurrent community acquired pneumonia. Scand J Infect Dis 1997;29:401-7. https://www.ncbi.nlm.nih.gov/pubmed/9360257

 

My 65 year old patient has had several bouts of bacterial pneumonia in the past 2 years. Her total serum immunoglobulins are within normal range. Could she still be immunodeficient?