Clinical aspects of Mycoplasma pneumoniae infection

301

LETTERSEDITOR to the

Case against antibiotic prophylaxis for dental treatment of patients with joint

adverse reactions to antibiotics when there is no evidence that such

prophylaxis is of any benefit is unacceptable.

prostheses SIR,-In 1991 the British Society for Antimicrobial Chemotherapy set up a working-party to consider whether patients with prosthetic joint implants (especially total hip replacements) should be given antibiotic cover to prevent late joint infection when undergoing dental treatment. The views of the working-party are reported here. Infection of prosthetic joints has been arbitrarily classified as early (within 3 months of joint replacement) or late.1 Most early infections are thought to be due to bacterial contamination of the site at operation, and perioperative systemic antibiotic prophylaxis reduces the infection rate. Late infections may be caused by the delayed growth of bacteria which gained entry at the time of operation or by bacteria carried in the blood to the joint from a distant site. Haematogenous spread has been demonstrated in animals. Blomgren and Lindgrenzinjected Staphylococcus aureus into the blood of rabbits and produced infection in cemented knee endoprostheses. However, to achieve these results it was necessary to inject inocula so large that 56-5% of the rabbits died. We and many others question the relevance of these findings to infection in man. Nevertheless, haematogenous infections have been known to follow active infections elsewhere in the body.3’ Patients with prosthetic joints who develop any intercurrent infection, especially of the skin, should therefore be treated promptly with antibiotics to which the infecting organisms are sensitive. Although many investigators have found no acceptable scientific evidence to support routine antibiotic prophylaxis for dental treatment for patients with prosthetic joints, the subject has remained controversial. Those who advise prophylaxis justify it on the basis that dental procedures can cause bacteraemia and bacteraemia can cause prosthetic joint infection. They point out that it is the accepted practice for prophylactic antibiotics to be given before some dental procedures to prevent endocarditis, and they believe that it is logical to do the same for patients with prosthetic hip replacements.s We do not agree: there are major differences between the two groups of patients and between the levels of risks

involved.

Joint infections have rarely been shown to follow dental procedures and are even more rarely caused by oral streptococci.6-8 In contrast there is clear evidence that bacteraemia induced by dental manipulations can cause endocarditis. First, up to 15% of cases of endocarditis follow dental procedures. Second, and more convincing, oral streptococci are the single largest group of infecting bacteria.9

Nevertheless, advocates of prophylaxis for patients with prosthetic joints may argue that even the faintest risk of infection after dentistry justifies their use because the consequences of infection can be devastating. Again we do not agree. Antibiotics may have severe side-effects and this cannot be ignored when administration of the drugs is unlikely to be beneficial. It has been estimated that 50 000 total hip replacements are carried out annually in the UK,1° and since these operations were introduced some 30 years ago the total number of patients with prosthetic joints must be substantial. Although some are old and edentulous, many still visit their dentists. Exposing them to risks of

N. A. SIMMONS, Department of Clinical Bacteriology, Guy’s Hospital, London SE1 9RT, UK Infectious Diseases Unit, Cameron Hospital, Fife

Chairman, Working Party of the British Society for Antimicrobial

Chemotherapy

A. P. BALL

of

Department Surgery, Guy’s Hospital, London

R. A. CAWSON

St Thomas’

Department of Clinical Microbiology, Hospital, London

S.

Orthopaedic Surgery Unit, Royal Postgraduate Medical School, London

S. P. F. HUGHES

Department of Oral Surgery, University of Glasgow

D. A. MCGOWAN

J. EYKYN

Department of Medical Microbiology, Charing Cross and Westminster Medical School, London

D. C. SHANSON

JW. The need for antibiotic coverage for dental treatment of patients with joint replacements. Oral Surg 1983, 55: 20-23. Blomgren G, Lindgren U. Late haematogenous infection in total joint replacement. studies of gentamicin and bone cement m the rabbit. Clin Orthop 1981; 155:

1. Little

2

244-48. 3. Ainscow DAP, Denham RA. The risk of

haematogenous infection in total joint replacements. J Bone Joint Surg 1984; 66B: 580-82. 4. Bell SM, Gatus BJ, Shepherd BD Antibiotic prophylaxis for the prevention of late infections of prosthetic joints. Aust NZJ Surg 1990; 60: 177-81. 5. Cioffi GA, Terezhalmy GT, Taybos GM. Total joint replacement: a consideration for antimicrobial prophylaxis. Oral Surg Oral Med Oral Pathol 1988; 66: 124-29. 6. Ching DWT, Gould IM, Rennie JAN, Gibson PH. Prevention of late haematogenous infection in major prosthetic joints. J Antimicrob Chemother 1989; 23: 676-80. 7. Lindqvist C, Slatis P. Dental bacteremia: a neglected cause of arthroplasty infections? three hip cases. Acta Orthop Scand 1985; 56: 506-08. 8. McGowan DA, Hendrey ML. Is antibiotic prophylaxis required for dental patients with joint replacements? Br Dent J 1985; 158: 336-38 9. Bayliss R, Clarke C, Oakley CM, Somerville W, Whitfield AGW, Young SEJ. The microbiology and pathogenesis of infective endocarditis. Br Heart J1983; 50: 10.

513-19. SPF. 10-15

Hughes

Prophylactic antibiotics in total joint replacement. Sem Orth 1986, 1:

Clinical aspects of Mycoplasma pneumoniae infection SIR,-Dr Alshafi and Dr Ironton (Dec 14, p 1519) describe two patients with Mycoplasma pneumoniae infection as unusual presentations in the absence of respiratory symptoms. These manifestations are well recognisedl but we agree that the infrequent reporting of such cases may be due to lack of awareness and possible misdiagnosis rather than to low incidence rates of non-respiratory M pneumoniae infection. Our interest in these infections, both from clinical and laboratory aspects, prompted us to examine retrospectively the clinical histories of 60 patients, 51 of whom attended hospital (45 as inpatients), with serologically diagnosed2 M pneumoniae infection during the 1990-91 epidemic. 7 patients (12%) referred to hospital had no respiratory symptoms. 3 had erythema multiforme, 2 had unexplained rashes,1 had gastroenteritis, and 1 had prolonged weight loss. None of the 7 was on appropriate therapy. Cough was predominant in 53 patients and skin manifestations were noted in 15 (25%). The rash was transient and truncal, spreading to the limbs but rarely affecting the face. A higher frequency of rash in males (60%) and in patients

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younger than 15 years (66%) accords with previous reports.3 6 patients had Stevens-Johnson syndrome, lesions appearing predominantly in the buccal cavity 10-14 days after onset. 3 patients older than 25 years were most seriously affected and readmission was necessary in 1 case because of prolonged inability to eat and drink due to severe mouth and oesophageal ulceration. One study suggests the prevalence of this syndrome may be at least 16%.’

Haemorrhagic labial crusting, previously reported as a prominent feature in many M pneumoniae cases, may be easily misdiagnosed as cold sores. Indeed, 2 patients in our series were diagnosed as having herpes simplex infection, despite the lack of substantive laboratory evidence, and were discharged on acyclovir. Only 2 patients with skin involvement were on appropriate therapy, indicating that M pneumoniae infection was not suspected. 6 patients had eye involvement (4 with Stevens-Johnson syndrome) and of 5 patients with ear symptoms, 2 had no respiratory involvement. CNS features were absent although in an earlier series we reported 1 patient with meningitis. CNS symptoms are regarded as immune-mediated rather than due to direct invasion or toxin production and, although brain antibodies are found in 71% of M pneumoniae cases with CNS symptoms compared with 45% without CNS involvement,5 no pathogenetic role has yet been attributed to them. We agree that clinicians should be aware of the protean manifestations of M pneumoniae infections, with or without respiratory involvement. We emphasise the importance of submitting clinical information to the laboratory so that investigations can be well directed. An audit of the notes of 25 patients revealed important omissions in the information submitted on laboratory request forms. The laboratory was notified of skin manifestations in only 44% of cases so affected and of eye and ear involvement in 0% and 20%, respectively. Respiratory symptoms were not mentioned for 14% of patients with them. Epidemics of M pneumoniae are periodic (every 4 years in the UK) and are predictable. Let us hope that increased awareness by clinicians and microbiologists will improve the management of patients in 1994-95. Virology Department, Public Health Laboratory, Norwich NR2 3TX, UK

MARGARET SILLIS

Department of Respiratory Medicine, West Norwich Hospital

BRIAN D. W. HARRISON

1. Ali NJ, Sillis M, Andrews BE, et al. The clinical spectrum and diagnosis of M pneumoniae infections. Q J Med 1986; 227: 241-51. 2. Sillis M. The limitations of IgM assays in the serological diagnosis of M pneumoniae infections. J Med Microbiol 1990; 33: 253-58. 3. Sontheimer RD, Garibaldi RA, Krueger GG. Stevens-Johnson syndrome associated with M pneumomae infection. Arch Dermatol 1978; 114: 241-44. 4. McCormack JG. M pneumoniae and the erythema multiforme-Stevens-Johnson syndrome. J Infect 1981; 3: 32-36. 5. Sillis M. The humoral response to Mycoplasma pneumoniae infections: some diagnostic implications. PhD thesis, University of East Anglia, Norwich, 1986.

Mood and

peak flow in asthma

SIR,-Ms Browne and Dr Highland (Jan 11, p 118) report a unique method to investigate the relation between mood and peak flow in asthma, but I think they come to the wrong conclusion. Both mood and peak flow improved for 2 days after the introduction of salbutamol (days 96 and 97), but deteriorated thereafter. The eventual improvement in both mood and peak flow took place from day 103 onwards. The onset of action of salbutamol is rapid, being within a few minutes of inhalation, and there is no evidence of a slower effect. This means that any benefit from the new treatment would be shown on the first day after its introduction, and there is no reason to believe that there is an increasing effect with time. If anything, the opposite might be true because of down-regulation of receptors. Thus, the evidence presented supports the opposite conclusion-namely, that a change in mood took place about a week after the introduction of salbutamol and that peak flow rose in association. Whatever the true explanation of these data, it is reassuring that the title of the report was neutral. Royal Brompton National Heart and Lung Hospital, London SW3 6NP. UK

DUNCAN M. GEDDES

Gallium

(aluminium) transferrin binding in Alzheimer’s disease

SIR,-DrMcGregor and colleagues (Nov 30, p 1394) state that in paper’ "no more than 20% [of gallium-67] was bound by transferrin, even in controls", implying that there was no difference between patients with Alzheimer’s disease (AD) and controls. We found that binding was 7-9% in AD and 17’ 1 % in controls, and it was this relative difference that was important, not the absolute levels of binding. These results could have been due to high transferrin-iron saturation, which was observed in the patients with low gallium-transferrin binding. There was no evidence that this was an "artifact" and, indeed, McGregor’s data confirm this in that they found that increasing iron saturation did reduce galliumour

transferrin binding. McGregor et al have studied few patients and their controls seem to be people screened for dementia as opposed to completely healthy individuals; they used serum where we used plasma; their incubation times were much longer; they used a Sephadex G100 column that is less sensitive; and they measured total iron-binding capacity (TIBC) not by measuring transferrin but by colorimetry, which could be affected by other factors. TIBC is itself a measure of the amount of transferrin in plasma and indirect assay methods are far from reliable ;2-4 direct measurement of transferrin is now the accepted standard method. Iron levels in the AD patients of McGregor et al were significantly less than those in their controls, unlike our results, and this would have influenced transferrin binding data. They also found no iron release from transferrin even at pH 4-7, which is at variance with other studies.6,7 Their citrate studies should not necessarily be interpreted as showing that citrate can displace aluminium or gallium from transferrin because they used concentrations 10-1000 times higher than those normally found in plasma. It is therefore not surprising that McGregor et al have not confirmed our results. We do not agree that our results can be ascribed to the way we did the measurements. Most gel-filtration systems cannot maintain truly physiological plasma conditions, and we accept that the conditions of our assay might not have been perfectly physiological. However, the same method was used for all samples, and no systematic methodological error of this type would consistently pick out particular groups of patients. Arbitrarily "correcting" pH or bicarbonate concentrations, for instance, before running such assays might eradicate the differences being investigated. We found only functional differences in transferrin, which need not necessarily be due to any intrinsic property of transferrin itself. In our original chromatographic method no bicarbonate was added. Subsequent studies in controls have shown that a bicarbonate concentration of 25 mmol/1 in the plasma and eluting buffer gives gallium-transferrin binding in the plasma of about 90%, as does pH 7-4, in keeping with other workers’ results, but the relative differences between controls and AD patients persist. Brammer et al9 followed our methodology precisely and confirmed our original observations. Dr Taylor and colleagues (Nov 30, p 1395) did not follow our methodology exactly. They do not state what sort of column was used; transferrin itself was not assayed; and serum, not plasma, was used. With gel-filtration their controls’ gallium binding was no different from their AD results, but these results were far lower than our controls’ results and very similar to our AD patients, which suggests a methodological problem. They also incubated samples with iron-55 for 36 days after the gallium studies but gallium-67 has got long-lasting beta activity, and this may have interfered with these results. Taylor et al claim that the order of samples on the column is important. This probably arose from failure to wash out the column completely and has not been a problem that we have encountered. We used control samples interspersed with study samples, and many of the measurements were done "blind".

McGregor, Taylor, and colleagues seem to agree that aluminium a greater extent in the brains of patients with

may accumulate to

mechanism for this is necessary. Our observations on gallium-transferrin binding in plasma provided one possible mechanism and neither of the above small studies constitute sound

AD,

so a