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S. pneumoniae

Streptococcus pneumoniae

Based on available data, the World Health Organization (WHO) estimates that Streptococcus pneumoniae (S. pneumoniae) kills close to half a million children under 5 years old worldwide every year, with most of these deaths occurring in developing countries.1  There are more than 90 strains (serotypes) of pneumococcus bacteria and it is the leading cause of community-acquired pneumonia (CAP) world-wide.2 It is also responsible for a myriad of other more common diseases including otitis media, sinusitis, and non-bacterimic pneumonia in addition to serious invasive pneumococcal diseases (IPD) such as bacteremia and meningitis.

Historically, the bacteria was first independently described by U.S. Army physician, George Sternberg, and the French chemist, Louis Pasteur, as roughly lancet-shaped pairs of coccoid bacteria identified  in human saliva. Previous reports identifying diplococci could be found in the literature, but only Sternberg and Pasteur established the pathogenic nature of these bacteria in animals. Later, the capsular polysaccharide of the bacterial cell wall was first detected in the urine of patients with pneumococcal pneumonia in 1917 by Dochez and Avery working at the Rockfeller Institute in New York City.3 It’s role in the serological activity of the bacteria has kept it as an important target used in the identification of the bacteria and diagnosis of the disease.

Although early and accurate diagnosis and treatment of pneumonia are associated with improved survival as well as significant reductions in the costs associated with unnecessary investigations and complications due to inappropriate treatments,4  the  currently available microbiological tests (e.g. sputum and blood cultures) remain  limited in clinical utility due to the both low sensitivity (reported  diagnostic yields as < 30% )5 and the delay in the availability of  culture results which can extend beyond 24 hours in some studies.2,5,6  Moreover, prior antibiotic use can reduce the relative diagnostic yield of blood cultures by 67% and sputum by 34%.4

Since studies indicate that patients who receive early antibiotic treatment (within 8 hours of hospital arrival) have a lower 30-day mortality4 and that early and precise antibiotic treatment may also decrease the community prevalence of antibiotic resistant bacteria and individual risks associated with Clostridium difficile infection,5 the increased sensitivity and rapid TAT (10 minutes or less) of next generation urinary antigen rapid tests as compared to culture and conventional rapid tests is of increasing clinical importance.

Transmission

Pneumococcal bacteria is spread from person to person by direct contact with respiratory secretions, like saliva or mucus. Approximately 4% of healthy adults and over 50% of children in some reports7,8 have S. pneumoniae as part of their commensal flora of their upper respiratory tracts,7,9 and thereby are considered asymptomatic carriers. Though colonization with pneumococci is mostly symptomless, it can progress to respiratory or even systemic disease if they are inhaled and is an important source of horizontal spread of the infection.1,9

Diagnosis

Routine laboratory diagnosis is performed by sputum gram stains and hemoculture for identifying pneumococcal pneumonia and determining antibiotic susceptibility. However, these conventional methods are relatively slow (over 24 hours) and insensitive, and show limited specificity. Other diagnostic tools include urinary antigen rapid tests for teichoic acid (polysaccharide of the cell wall of the bacteria).4

Treatment

Treatment will usually include a broad-spectrum cephalosporin, and often vancomycin, until results of antibiotic sensitivity testing are available which can take up to 24 hours or beyond. Data show that pneumococcal bacteria are resistant to one or more antibiotics in 30% of cases.9

Resistance to penicillin and other antibiotics was previously very common. However, as result of a re-evaluation that showed the response of the bacteria to penicillin is preserved in clinical studies despite reduced susceptibility response in vitro, susceptibility breakpoints for S. pneumoniae  (CLSI) January 2008 ) have been revised and implemented.9 U.S. and international guidelines continue to recommend penicillin or amoxicillin as drugs of choice for pneumococcal pneumonia as opposed to community acquired pneumonia without etiological identification for which broad spectrum  antibiotics are still used.8, 10  For this reason, rapid detection of S. pneumoniae to enable the immediate administration of targeted, specific antibiotic treatment has become crucial in the reduction of the unnecessary usage of powerful broad spectrum antibiotics, thereby potentially decelerating the emergence of antibiotic resistant strains of bacteria to these important therapies.

References

  1. http://www.who.int/mediacentre/factsheets/fs331/en/
  2. Rello, J. Lisboa, T, Luan M., Gallego, M., Kee, C., Kay I., Lopez, D., Waterer, GW, 2015. Severity of Pneumococcal Pneumonia Associated with Genomic Bacterial Load. Chest. 832-840.
  3. Watson, D. Musher M., Jacoboson J, and Verhoef, J. A Brief History of the Pneumococcus in Biomedcal Research a Panopoly of Scientific Discovery.  Clinical Infectious Disesases 1993; 17;913-924.
  4. Song, JY, Eun, BW, Nahm, M., 2013. Diagnosis of pneumococcal Pneumonia: Current Pitfalls and the Way Forward. Infect Chemother 45(4);351-366
  5. Sinclair, A., Xie, X., Teltscher, M., Dendukurie, N. 2013. Systematic review and Meta-Analysis of a Urine Based Pneumonococcal Antigen Test for Diagnosis of Community Acquired Pneumonia Caused by Strpetocococcus pneumoniae. Journal Clin Micr. 2303-2310.
  6. Neuman M, Harper, M., 2001. Time to positivity of blood cultures for children with Streptococcus pneumoniae bacteremia. CID 33.1324-8.
  7. Harboe, Z., Slotved H., Knonradsen, H., Kaltoft, S.  A Pneumococcal Carriage Study in Danish Pre-school Chinldren before the Introduction of Pneumococcal Conjugate Vaccination. The Open Microbiology Journal, 2012, 6 40-44
  8. Matta, M., Kerneis, S. et al.  Do clinicians consider the results of the Binax NOW Streptococcus pneumoniae urinary antigen test when adapting Antibiotic regmines for pneumonia patients?, Clin Microbiol infect 2010.; 16 1389-1393.
  9. Bogaert, D., de Goot R de, and PW M Hermans.  Streptococcus pneumoniae colonization: the Key to pneumococcal disease.  The Lancet. Vol 4 March 2004.
  10. Mandell LA, Wunderink  RG, Anzueto A. et. Al. Infectious Disease Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect. Dis 2007; 44(suppl)S27-72