An elderly man with a background of ischaemic heart disease, severe aortic stenosis and type 2 diabetes mellitus presented following recent travel from Hong Kong with shortness of breath and hypoxia. A chest X-ray confirmed left lower lobe consolidation (CRP 502, WCC 22) and he was commenced on broad spectrum antibiotics (Tazocin and Clarithromycin). Over the following 12 hours he deteriorated on the ward, with worsening hypoxia, hypotension and anuria.

He required emergency admission to intensive care for intubation and ventilation, and required inotropic support. He developed a severe metabolic acidosis and rising lactate, for which  haemofiltration was commenced. Vasopressin was added, followed by dobutamine, and hydrocortisone started for inotrope resistant hypotension. He remained ventilated on 100% oxygen, with high pressure support. He had a positive pneumococcal antigen, and high dose benzylpenicillin was added to his antibiotic regime, along with Oseltamivir (Tamiflu). Despite 12 hours of intensive therapy his acidosis worsened and he failed to respond to increasing doses of inotropic support, dying 30 hours after presentation to hospital.

What are the clinical features of pneumococcal sepsis?

Katherine Francis

Streptococcus pneumoniae continues to be the leading infective organism of adult community-acquired pneumonia (CAP), accounting for approximately 30% of episodes of CAP in most series.¹ Mortality from pneumococcal pneumonia despite effective antimicrobial treatment has remained unchanged in the past decade, and is about 10% in non-bacteraemic pneumonia and up to 30% in bacteraemic pneumonia, in the elderly, and in severe pneumonia.

Pneumococcal pneumonia carries a high mortality and morbidity rate and national vaccination programmes have been introduced to try to reduce this in those thought to be susceptible to pneumococcal disease. This group includes babies and infants, adults over 65 years old, post-splenectomy or asplenic patients, those with chronic disease or immunosuppressed patients.

A report by Van der Poll and Opal² in 2009 states pneumococcus is still the leading cause of community acquired pneumonia worldwide due to versatility in the genome and it’s polygenic virulence capabilities, meaning that a multi-faceted approach with vaccination, combinations of antibiotics and immunoadjuvant therapies are all needed to control it.

There are suggestions there may be genetic differences in susceptibility to pneumococcal infection. Sun et al³ found differences in alveolar macrophage bacterial killing and hence a reduced bacterial clearance from the respiratory tract between two genetically different varieties of mice. Studies in human populations have identified a number of genes that carry phenotype associated polymorphisms. Jonczyk et al⁴ also found that gene expression in pulmonary vasculature and immune cells play an important role in resisting pneumococcal infection. They propose that a mediated regulation of fibroblast differentiation is important in the susceptibility to invasive pneumococcal disease.

Harbarth et al⁵ report a 20% mortality in a retrospective case cohort study of nearly 2000 patients who were admitted with severe pneumococcal sepsis or septic shock and treated with antibiotic monotherapy, although this figure hardly changed (19.5%) when antibiotic combination therapy was used.

A prospective study in Spain in 1996-98 looked at 101 patients admitted with probable or confirmed pneumococcal pneumonia trying to identify factors predictive of outcome.¹ Overall, 26% of patients were admitted to the ICU and mortality was 11%. Factors significantly associated with mortality in univariate analysis included systolic blood pressure < 90 mm Hg and confusion at admission, as well as septic shock, renal failure, and requirement for mechanical ventilation at any time (mortality 25%). In multivariate analysis including the five variables significantly associated with death, confusion and renal failure were shown to be independently associated with death. Antibiotic resistance (to penicillin or cephalosporins) had little effect on overall mortality, hospital stay, APACHE II score on admission to ICU or the need for mechanical ventilation.

Both Norway and the United States of America have implemented and reported on vaccination programmes for pneumococcal disease in children, showing that the incidence of invasive pneumococcal disease declined rapidly in the 2 years after introduction of the vaccine⁶, and hospital pneumonia admission rates declined in the USA by 39% in children under the age of 2, equivalent to 506 per 100,000 children.⁷ The admission rate specifically for pneumococcal disease declined by 65%.

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Lessons learnt

This patient fitted all the criteria for immunization, given his age and co-morbidities. On presentation to hospital, he was treated with broad spectrum antibiotics within one hour of presentation to hospital, but continued to deteriorate into multi-organ failure over the course of the next 12 hours on the ward. This potentially could have been recognized sooner, although may not have altered the outcome. His severe aortic stenosis created a fixed cardiac output state, with no compensatory mechanisms, on top of long standing immuno-suppression from the diabetes mellitus. Despite maximal therapy, overwhelming pneumococcal sepsis caused vasopressor resistant shock and acidosis and he died. Perhaps both primary and secondary care need to be involved in identifying patients at risk and targeting primary prevention strategies.

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References

1. S Ewig, M Ruiz, A Torres et al. Pneumonia Acquired in the Community Through Drug-Resistant Streptococcus pneumonia. American Journal of Respiratory and Critical Care Medicine, Vol. 159, No. 6 (1999), pp. 1835-1842
2. Van Der Poll T, Opal S. Pathogenesis, treatment and prevention of pneumococcal pneumonia. Lancet (Oct 2009), 374:1543-56
3. Sun K, Gan Y Metzger D. Analysis of Murine Genetic Predisposition to Pneumococcal Infection revelas a Critical Role of Alveolar macrophages in Maintaining sterility of the Lower Respiratory Tract. Infect. Immun. May 2011; 79(5):1842-1847
4. Jonczyk M, Simon M, Kumar S. Genetic Factors Regulating Lung Vasculature and Immune Cell Functions Associated with Resistance to Pneumococcal Infection. Mar 3  2014. DOI 10.1371/journal.pone.0089831
5. Harbarth S, Garbino J, Pugin J et al. Lack of effect of combination antiobiotic therapy on mortality in patients with pneumococcal sepsis. Eur J Clinical Microbiology and Infectious Diseases (Oct 2005), 24: 688-90
6. Vestrheim D, Lovell O, Aaberge I. Effectiveness of a 2+1 dose schedule pneumococcal conjugate vaccination programme on invasive pneumococcal disease among children in Norway. Vaccine (2008) 26; 3277-81
7. Grijalva C, Nuorti J, Arbogast P et al. Decline in pneumonia admissions after routine childhood immunization with pneumococcal conjugate vaccine in the USA. Lancet 2007 369; 1179-86.