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Antibiotic susceptibility of streptococci and related genera causing endocarditis: analysis of UK reference laboratory referrals, January 1996 to March 2000

Alan P Johnson, clinical scientist ^a, Marina Warner, biomedical scientist ^a, Karen Broughton, biomedical scientist ^b, Dorothy James, data administrator ^a, Androulla Efsratiou, clinical scientist ^b, Robert C George, consultant microbiologist ^b, David M Livermore, clinical scientist ^a. 

^a Antibiotic Resistance Monitoring and Reference Laboratory, Central Public Health Laboratory, Colindale, London NW9 5HT, ^b Streptococcus and Diphtheria Reference Unit, Respiratory and Systemic Infection Laboratory, Central Public Health Laboratory

Correspondence to: A P Johnson Ajohnson{at}phls.nhs.uk

A combination of penicillin and gentamicin is recommended for streptococcal endocarditis by both the Endocarditis Working Party of the British Society for Antimicrobial Chemotherapy and the American Heart Association, with vancomycin replacing penicillin for those who are allergic to penicillin. ^{1 2} The Public Health Laboratory Service's Antibiotic Resistance Monitoring and Reference Laboratory and Streptococcus and Diphtheria Reference Unit routinely test bacteria referred from cases of endocarditis from a wide range of hospitals, representing about 15% of all UK isolates from endocarditis. We retrospectively analysed the species distribution and antimicrobial susceptibility of streptococci and related bacteria from patients with endocarditis received over 4.25 years; enterococci have been reviewed previously.³

	Methods and results

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Isolates from confirmed cases of endocarditis referred between January 1996 and March 2000 were identified from the reference laboratory's database, which provides antibiotic susceptibility as minimum inhibitory concentrations of each antibiotic for each isolate. Isolates were categorised as susceptible or resistant using published criteria.⁴

Data were available for 607 non-duplicate isolates, comprising 26 genera or species, referred from 168 UK hospitals (table). Most (86%) of the isolates were "viridans" group streptococci, which are documented as the commonest agents of endocarditis.⁵ Five species accounted for over two thirds of the isolates. Among these, 13% of Streptococcus oralis isolates, 14.5% of S sanguis, and 5.5% of S gordonii had reduced penicillin susceptibility (minimum inhibitory concentrations greater than 0.125 mg/l), whereas all S bovis type I and S mutans isolates were susceptible. Other species and genera comprised fewer than 20 isolates each, precluding meaningful calculation of percentage resistance. None the less, it was notable that both isolates of Abiotrophia defectiva and six of 15 isolates of A adjacens had reduced susceptibility to penicillin. All isolates of S pneumoniae and Lancefield groups A, B, C, and G streptococci were susceptible to penicillin.

Overall, 88.8% of the isolates were susceptible to penicillin (minimum inhibitory concentrations 0.125 mg/l), and minimum inhibitory concentrations of 0.25 mg/l were seen for another 4.4%. Minimum inhibitory concentrations of 4-8 mg/l were seen for only seven isolates (1.2%). All of the isolates were susceptible to vancomycin and teicoplanin (minimum inhibitory concentrations 0.5 to 2 mg/l) and none had high level resistance (minimum inhibitory concentration greater than 2000 mg/l) to gentamicin.

	Comment

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Although the clinical data available to our reference laboratory are sometimes limited and there is a potential for submission bias, we believe that our analysis is the most comprehensive possible for streptococcal endocarditis. The data confirm the dominance of "viridans" streptococci and indicate that whereas a few (1.2%) have substantial penicillin resistance, most remain fully susceptible. Some guidelines advocate that endocarditis of a native valve caused by streptococci that are susceptible to penicillin should be treated for two weeks with penicillin plus gentamicin, provided patients lack thromboembolic disease and cardiac risk factors, have small vegetations, and respond clinically within the first week.¹ In patients not fulfilling these criteria or with infection of a prosthetic valve, four weeks of penicillin plus gentamicin is recommended. Treatment for at least four weeks is also advocated for patients with streptococci with reduced susceptibility to penicillin: the British Society for Antimicrobial Chemotherapy advocates penicillin plus gentamicin for four weeks when the minimum inhibitory concentration of penicillin exceeds 0.1 mg/l; the American Heart Association advocates penicillin for at least four weeks, with gentamicin for the first two weeks if the minimum inhibitory concentration of penicillin is 0.25 mg/l or for at least four weeks if it exceeds this value.

Although reduced susceptibility to penicillin was noted in about 11% of our isolates, with 1.2% substantially resistant, none showed resistance to vancomycin or high level resistance to gentamicin, which would abolish synergy in combined treatments. Although reduced susceptibility to penicillin has implications for the duration of treatment, penicillin and gentamicin remain appropriate for most patients, with vancomycin and gentamicin a universally active alternative for those who are allergic to penicillin or who have more resistant isolates.

	Acknowledgments

Contributors: APJ conceived the idea for the project, collected and analysed the data, and drafted the paper; he will act as guarantor for the paper. MW performed the antibiotic susceptibility tests. KB and AE speciated the bacterial isolates. DJ assisted in collection and collation of the data. DML and RCG contributed to discussions.

	Footnotes

Funding: Public Health Laboratory Service.

Competing interests: None declared.

This article is part of the BMJ's randomised controlled trial of open peer review. Documentation relating to the editorial decision making process is available on the BMJ's website

	References

Top Methods and results Comment References

1.	Working Party of the British Society for Antimicrobial Chemotherapy. Antibiotic treatment of streptococcal, enterococcal, and staphylococcal endocarditis. Heart 1998; 79: 207-210[Free Full Text].
2.	Wilson WR, Karchmer AW, Dajani AS, Taubert KA, Bayer A, Kaye D, et al. Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. JAMA 1995; 274: 1706-1713[Abstract/Free Full Text].
3.	Johnson AP, Warner M, Woodford N, Speller DCE, Livermore DM. Antibiotic resistance among enterococci causing endocarditis in the UK: analysis of isolates referred to a reference laboratory. BMJ 1998; 317: 629-630[Free Full Text].
4.	Working Party of the British Society for Antimicrobial Chemotherapy. A guide to sensitivity testing. J Antimicrob Chemother 1991; 27(suppl D): 1-50[Free Full Text].
5.	Dyson C, Barnes RA, Harrison GA. Infective endocarditis: an epidemiological review of 128 episodes. J Infect 1999; 38: 87-93[CrossRef][Medline].

(Accepted 27 October 2000)