Department of Microbiology Bacteraemia Guideline

Pneumococcal (Streptococcus pneumoniae) bacteraemia

• Aim
• Background
• About Streptococcus pneumoniae
• Antimicrobial susceptibilities
• Clinical differential diagnosis
• Antimicrobial treatment
• Supplementary Information

Quick reference guide to the management of Pneumococcal bacteraemia

This document provides guidelines for doctors on the management of patients with confirmed bacteraemias (blood cultures). This document is supplementary to, and should be used in conjunction with, the antimicrobial guidelines.

Species: Streptococcus pneumoniae

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Aim

The aim of this guideline is to:

• Provide education to junior microbiology registrars
• Support communication of blood culture results from microbiologists to ward doctors
• Support ward doctors in treating and investigating bacteraemic patients

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Background

The blood culture process: Timings of culture, identification, susceptibility tests and clinical liaison.
How to use this guideline: This guideline should be used to help in the management of patients with a confirmed bacteraemia. The guideline should be used to support interaction with specialist advice e.g. Microbiology.

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About Streptococcus pneumoniae

The organism:
Streptococcus pneumoniae (also called Pneumococci) are encapsulated Gram positive organisms. They are usually seen in pairs (diplococci) on microscopy. There are more than 90 different serotypes.

Natural habitat:
The normal habitat of pneumococci is the nasopharynx of humans; most children and a minority of adults will be asymptomatically colonised with pneumococci. In the UK colonisation prevalence amongst children is approximately 50%. The duration of colonisation is variable but in most instances it is between 1 and 6 months.

Virulence factors:
The polysaccharide capsule is the major virulence factor. It inhibits phagocytosis of the organism by macrophages. Pneumococci produce a protease (IgA1) which helps them evade the protective functions of mucosal antibodies (IgA) in the upper respiratory tract. Pneumococci also produce a toxin called Pneumolysin. This inhibits neutrophil chemotaxis, phagocytosis, lymphocyte proliferation and immunoglobulin synthesis.

Risk factors for disease:
The risk of pneumococcal disease is highest in infancy, declining throughout the first 5 years of life. The risk of disease rises again from the age of 50 years onwards. Risk of disease is related to exposure, development of colonisation and the hosts own resistance to invasion. Increased exposure is seen in crowded environments (military barracks, homeless shelters, prisons etc..). Chronic medical conditions predispose to invasion of the organism. Alcoholism is consistently associated with pneumococcal disease. HIV infection increases the risk of invasive pneumococcal disease and is also associated with recurrent pneumococcal disease. Influenza and other respiratory viral infections also increase the risk of invasive pneumococcal disease. Asplenic or patients with a dysfunctional spleen are at increased risk of pneumococcal disease. Encapsulated organisms such as pneumococci need to undergo opsonisation by antibody in order for the host’s immune system to remove them; the spleen plays a vital role in this process.

Transmission of disease:
Pneumococcus is transmitted by those colonised, particularly pre-school children. This is through direct contact with nasal secretions or infected fomites (i.e. hands). Outbreaks of pneumococcal pneumonia do occur; this suggests that airborne dissemination, facilitated by coughing is another mechanism of spread.

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Antimicrobial susceptibilities

Pneumococci are usually susceptible to the β-lactam antibiotics (Penicillin, Cephalosporin’s, Carbapenens) and Macrolides (Erythromycin, Clarithromycin). Alternative agents includeLevofloxacin and Vancomycin.

Penicillin Resistance:
Pneumococci are characterised as being either:

• Fully susceptible
• Intermediately resistant
• Fully resistant

Your antibiotic choice under these circumstances will depend on the source of the pneumococcal infection.
For CNS sources (i.e. meningitis) Penicillin should not be used unless the isolate is fully susceptible.
For non-CNS sources (i.e. pneumonia) Benzylpenicillin/Amoxicillin may still be used for treatment if the isolate is intermediately resistant.

For isolates which are not fully susceptible it is advised to discuss antimicrobial therapy with a microbiologist.

Epidemiology of Penicillin resistance:
Surveillance data from the European centre for disease control (eCDC) demonstrates that in 2012, there were three countries with high rates (25-50%) of Penicillin resistant Pneumococci. Spain, Romania and Bulgaria. Countries with moderate levels of resistance (5-10%) were Portugal, Italy, Latvia and Slovakia. In the UK <1% of="" our="" pneumococcal="" isolates="" are="" penicillin="" resistant. It is important to highlight that this data comes from participating countries only; submission of isolates to the European surveillance scheme is voluntary. Up to date European resistance rates are available at the ECDC website: http://www.ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/database/Pages/database.aspx

Global prevalence and distribution of Penicillin Resistant Pneumococci is patchy. Developing countries can rarely conduct population based surveillance for Pneumococcal resistance and adequate demographic detail is not always available. Data from the SENTRY antimicrobial surveillance program highlighted that in North America 20-35% of Pneumococcal isolates were non-susceptible to Penicillin. In Latin America 15-60% of pneumoccoal isolates were non-susceptible with the highest rates seen in Mexico and Uruguay. Non-susceptible includes isolates which are intermediately resistant and fully resistant. *

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Clinical differential diagnosis

The differential diagnosis for Pneumococcal bacteraemia includes the following:
Note: These conditions do not necessarily occur in isolation; pneumococcal meningitis is quite frequently accompanied by pneumonia.

• Pneumonia
• Empyema - This occurs in 2-5% of patients with established pneumococcal pneumonia.
• Meningitis
• Otitis media
• Sinusitis
• Septicaemia – Acute septicaemia is an uncommon manifestation of Pneumococcal disease; it is encountered most frequently in immunocompromised or asplenic/hyposplenic patients.
• Endocarditis & Pericarditis – Cardiac manifestations are well described but rare, occurring in less than 1% of all pneumococcal infections.
• Peritonitis – This is an uncommon condition encountered in three risk groups. Patients with cirrhosis of the liver or nephrotic syndrome. Patients with gastrointestinal disease such as appendicitis or peritoneal dialysis and otherwise healthy young girls, possibly as a complication of pelvic infection.
• Osteomyelitis and Septic Arthritis
• Catheter related bloodstream infections
• Austrian syndrome: An uncommon triad of pneumonia, endocarditis and meningitis. When pneumoccal meningitis and pneumonia are diagnosed consideration should be given to investigating for endocarditis.

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Antimicrobial treatment

It is important to determine whether the patient has risk factors for Penicillin resistance to ensure appropriate empirical antimicrobial therapy is selected, see Epidemiology of Penicillin resistance. Empirical regimens for patients with risk factors for penicillin resistant pneumococci should be discussed with microbiology. Please note antibiotic guidance for meningitis in patients with risk factors for Penicillin resistance can be found in the meningitis guidelines. Antibiotic therapy should always be reviewed with results of susceptibility tests. Allergy status and the likely source of infection should always be considered when prescribing antibiotics.

The table below outlines some of the common infections associated with each of the clinical syndromes. Please be aware that pneumococci can present in unusual ways, and that this list is by no means exhaustive

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Supplementary Information

Consider further investigations as appropriate to elicit the source of infection, please see relevant guidelines.

Vaccination:
Two vaccines for the prevention of pneumococcal disease are available:
Pneumococcal polysaccharide vaccine (PPV) & Pneumococcal conjugate vaccine (PCV)
Further information and guidance on indications for vaccination is available from The Green Book:
https://www.gov.uk/government/publications/pneumococcal-the-green-book-chapter-25