Journal of Infection (I992) z5, 77-8x

CASE REPORT Prosthetic hip-joint infection associated with a penicillin-tolerant group B streptococcus R. C u n n i n g h a m , * C. Walker~ and E. Ridgway*

Departments of * Medical Microbiology and Jf Orthopaedic Surgery, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, U.K. Accepted for publication 27 November I991 Summary We report a case of prosthetic hip-joint infection with Streptococcus agalactiae (Lancefield group B streptococcus). The infection recurred after 3 months' treatment with amoxycillin. On further investigation, the isolate was found to be amoxycillintolerant. Addition of gentamicin abolished tolerance in vitro and the patient has remained asymptomatic since receiving a Io-day course of amoxycillin and gentamicin followed by amoxycillin alone.

Introduction G r o u p B streptococci are a c o m m o n cause of serious neonatal and maternal infection. R e c u r r e n t episodes of bacteraemia have been reported in neonates and some workers have ascribed the recurrence to penicillin tolerance} Such tolerance is defined as a minimal bactericidal concentration ( M B C ) which is 32 or m o r e times greater than the minimal inhibitory concentration ( M I C ) . T h e reported incidence of penicillin tolerance in group B streptococci varies from 4-13 0/O.i-2 Previous case reports have highlighted treatment failures despite standard doses of beta-lactam antibiotics. While it is reasonable to assume that penicillin tolerance m a y have c o n t r i b u t e d to treatment failure, the presence of an abscess, inadequate dosage or duration of treatment may have also been implicated. W e report a case of recurrent group B streptococcal infection in a prosthetic hip joint, the m a n a g e m e n t of which was influenced by the laboratory finding of penicillin tolerance.

Case report A 75-year-old m a n with osteoarthritis of both hip joints had a primary, cemented, left total hip-joint replacement in I98O without post-operative complications and with excellent function w h e n seen at s u b s e q u e n t reviews. In 1987 he u n d e r w e n t a similar p r o c e d u r e on the right hip joint. T e n years after his initial replacement he presented with a 12 hours' history of acute pain in the left hip without any preceding trauma. H e was febrile (38"4 °C) with a W B C count of 23"9 × IOg/1. Blood cultures grew a group B beta-haemolytic oi63-4453/92/o40o77 + 05 $03.00/0

© I992 The British Society for the Study of Infection

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R. C U N N I N G H A M

ET AL.

streptococcus. Intravenous treatment with amoxycillin 5oo mg 8-hourly was started. T h e r e was no evidence of a dental, urinary tract or endocardial focus for the infection. Clinically, the patient improved markedly within 3 days and by day 5 his WBC count had fallen to 9"8 × Iog/1. A Technetium 99 bone scan was normal but a Gallium 67 scan showed abnormal uptake related to the left hip prosthesis (Plate I). Nine days after his admission to hospital, antibiotic therapy was changed to amoxycillin 25o mg 8-hourly orally and he was discharged with this dose. Antibiotic therapy was continued with good compliance but 3 months later the patient presented with another episode of pain in the left hip, slight fever (37"5 °C) and a WBC count of I2"4 x IO9/1. He was still taking amoxycillin but this was stopped before blood cultures were repeated. T h e following day he developed a rigor with fever (38'5 °C) and increasing pain in the hip. Treatment with amoxycillin 5oo mg 8-hourly intravenously was resumed. Blood cultures taken on admission were sterile but those taken during the rigor again grew group B streptococci. Five days later, when the isolate was found to be amoxycillin-tolerant, the dose of amoxycillin was increased to I g 8-hourly and combined with gentamicin I6O mg daily. This combination was continued for Io days. T h e patient's clinical condition improved dramatically and he was discharged on oral amoxycillin 3 g twice daily. This was well tolerated and was continued for a further 3 weeks, after which the dose was reduced to 5oo mg, three times daily. T h e patient remained free of symptoms and with good function of the hip joints when seen at review 6 months later.

Microbiology Group B beta haemolytic streptococci were isolated from the aerobic bottle of a single set of blood cultures performed at the time of the patient's first admission to hospital. T h e isolate was grouped by means of the Streptex latex agglutination method (Wellcome Diagnostics, Dartford, Kent, U.K.). It was sensitive to penicillin, erythromycin, trimethoprim, vancomycin and gentamicin on disc testing. An identical organism was isolated from aerobic and anaerobic bottles of a set of blood cultures performed during the patient's second admission to hospital. M I C s and MBCs of amoxycillin alone and in combination with gentamicin o'5 mg/1 were determined by the broth-dilution method. Isosensitest broth (Oxoid, Basingstoke, U.K.) was used. T h e Oxford staphylococcus ( N C T C 675I) was tested in parallel and all estimations were done in duplicate. An inoculum of 5 x io ~ C F U was used and 20 #1 samples from tubes not showing growth after overnight incubation were inoculated on 5 % horse blood agar. T h e MBC was taken as the lowest concentration producing 99"9 % killing. M I C and MBC values are given in Table I. T h e MBC > 8 mg/1 indicates that killing of the organism would not be possible with clinically achievable concentrations of amoxycillin. T h e addition of gentamicin, even at ' t r o u g h ' concentrations of o"5 mg/1 abolished the tolerance completely~ so reducing the MBC to o'I2 5 mg/1.

7ournal of Infection

Plate I

Plate I. (a) T h i s isotope bone-scan of the pelvis and upper femora taken 3 h after injection of T e c h n e t i u m 99 does not show any increase in uptake at the site of the left hip prosthesis. T h e r e is marked activity in the region of the bladder, centrally, and some increase in uptake on the right in an area of bony n o n - u n i o n following trochanteric osteotomy for insertion of the right hip prosthesis. (b) T h i s Gallium 67 bone scan, which is more specific for infection t h a n that of Plate (a), shows an increase in uptake over the left hip prosthesis. T h e stippled area in the diagram identifies this in relation to the pelvis and hips.

R. CUNNINGHAM ET AL.

(Facing p. 781

Group B streptococcal osteomyelitis

79

Table I MIC and MBC of amoxycillin alone and in combination with

gentamicin (o'5 mg/l) in respect of group B streptococcus Amoxycillin/gentamicin MIC

and MBC

Amoxycillin

MICMBc

Amoxycillin + gentamicin 0. 5 mg/1

MIC

0"06

MBC

o'I25J

> o'o68.o}

Ratio

~-

> I33

Ratio = 2

:-256

g gt~

128

i 3

.c ._o E

2

I6

] I0 pm

6am

2 pm

I0 pm

Post amoxyciltin Post omoxycillin Pre amoxycillin Pre omoxycillin O,5g

1.0 cJ Gentamicin

I-0 g

bOg

concentration I00 mg

Fig. I. Serial gentamicin concentrations as well as serum inhibitory and cidal titres to group B streptococcus. Samples were taken after the last dose of amoxycillin 5oo mg and throughout the first day of treatment with amoxycillin I g 8-hourly and gentamicin I6o m g once daily. ( ~ ) , cidal; (N), inhibitory; ('A'), gentamicin concentration.

Concentrations of gentamicin as well as serum inhibitory titres ( S I T ) and serum cidal titres ( S C T ) were estimated on a sample of blood taken I h after a dose of 50o m g amoxycillin alone and on serial samples obtained throughout the first day of treatment with gentamicin c o m b i n e d with the higher dose of amoxycillin (Fig. I). F o l l o w i n g a dose of 50o m g amoxycillin alone, the difference between the S C T and S I T was eight-fold, but no more than t w o - f o l d after the addition of gentamicin.

80

R. C U N N I N G H A M E T A L .

Discussion

Antibiotic tolerance of group B beta-haemolytic streptococci has been reported previously in isolates from both adults and neonates b u t has never conclusively been shown to affect therapeutic outcome. Siegal e t a l . , 3 reported two cases o f serious penicillin-tolerant group B streptococcal infection in neonates, one of w h o m had a cerebral abscess, the other septicaemia. In both cases, infection recurred despite standard doses of penicillin and gentamicin. Since the first patient r e s p o n d e d to drainage of the abscess and the second to a prolonged course of ampicillin and gentamicin in normal doses, however, failure of treatment cannot with certainty be ascribed to antibiotic tolerance. K i m and A n t h o n y 1 f o u n d four tolerant strains in their series of i o o cases but, since all four patients died within 2 4 h of the onset of illness, penicillin tolerance was unlikely to have been relevant. T h e only report o f tolerance to penicillin by group B streptococci in Britain is in the series published by Broadbent. 2 Isolates from blood or cerebrospinal fluid of 38 patients were tested. Five were f o u n d to be tolerant b u t details of treatment or o u t c o m e were not given. Total hip-joint replacement is a successful way of improving function by eliminating pain and allowing reasonable m o v e m e n t o f the joint. C e m e n t e d prostheses may, however, act as a nidus for recurrent infection. Careful operative technique, clean air systems in the operating theatre and prophylactic antibiotics m a y reduce the early infection rate to 0-6 %.4 Late haematogenous infection m a y also arise, often after dental or urological p r o c e d u r e s ) Although, initially, our patient appeared to respond to standard doses of amoxycillin, it is evident, in retrospect, that the focus of infection in his prosthesis was not eliminated. T h e treatment of choice in such a situation is removal and, ideally, exchange of the prosthesis. 6 U n f o r t u n a t e l y , this carries significant morbidity, so, in view of his age and poor general condition, it was felt that the risks to our patient were too great. Instead, he was treated with a higher dose of amoxycillin c o m b i n e d with gentamicin, followed b y amoxycillin alone, the intention being to continue this treatment indefinitely in the absence o f any adverse reactions. Infection of a prosthesis is a rare b u t disastrous complication of joint replacement. This case illustrates the importance of close liaison b e t w e e n surgeon and microbiologist in its management. W e suggest that for bacteria isolated from infected prostheses M I C s and M B C s o f beta-lactam antibiotics should always be determined. T r e a t m e n t of beta-lactam antibiotic-tolerant strains should be with an agent or a combination of agents k n o w n to achieve bactericidal concentrations in the serum. (We thank Mr I. C. M. Gray for allowing us to report on his patient as well as Dr G. Smith and Professor A. Percival for advice and assistance.)

References x. Kim Kwang S, Bascombe FA. Penicillin tolerance in group B streptococci isolated from infected neonates. 3* Infect Dis 1981; 144 : 411-419.

Group B streptococcal osteomyelitis

8I

2. Broadbent A. Penicillin tolerance in group B streptococci. J Antimicrob Chemother 1984; I3 : 396-397. 3. Siegel JD, Shannon KM, DePasse MT. Recurrent infection associated with penicillintolerant group B streptococci: a report of two cases. J Pediatr 1981; 99: 920-924. 4. Lidwell O, Lowbury E, Whyte E. Effect of ultraclean air in operating rooms on deep sepsis in the joint after total hip or total knee replacement. Br Med J 1982; z85: 928-932. 5. Stinchfield F, Biigliani L, Neu H, Goss T, Foster C. Late haematogenous infection of total joint replacement, ff Bone Joint Surg [Am] 198o; 6z-A: 1345-135o. 6 Buchholz HW, Elson R, Engelbrecht E. Management of deep infection of total hip replacement, ff Bone Joint Surg [Br] 1981; 63: 342-353.