278
Proc. roy. Soc. Med. Volume 70 April 1977
sometimes calcification of necrotic tumour (Hsieh & Hsieh 1936). Metastatic spread occurs in only 10% of cases and the condition is usually fatal because of local invasion. Treatment by complete surgical removal offers the best chance of cure (MacCarty et al. 1961), but resectability is often limited by involvement of the sacral plexus, the upper nerve roots of which must be preserved to maintain sphincter control. Radiotherapy has been recommended where complete excision is not possible (Pearlman & Friedman 1970), and it is useful for palliation of pain due to recurrent disease, which may be delayed for many years (Sennett 1953).
Table I Investigations ESR varied between 26 and 56 mm (Westergren) in the 1st hour Chest X-ray, IVP, liver function tests, white cell count, urea and electrolytes were all normal Barium meal and follow-through showed a large duodenal diverticulum but no other pathology Latex test, ANF, LE cells and stool for examination and culture were all negative Agglutination tests for salmonella and brucella, 1: 20 Toxoplasma dye test negative Cytomegalovirus CF antibody titre, 1: 32 BSP excretion test: 5 % dye retained after 45 min Liver biopsy failed Sternal marrow normal Lymphangiogram: non-specific normal appearances No acid-fast bacilli seen or grown from urine or sputum Laparotomy was carried out on 5 February 1975
REFERENCES Freier D T, Stanley J C & Thompson N W (1971) Surgery, Gynecology and Obstetrics 132, 681-686 Gray S W, Singhabhandhu B, Smith R A & Skandalakis J E (1975) Surgery 78, 573-582 Hennig L (1900) Beitrage zur pathologischen Anatomie und zur allgemeinen Pathologie 28, 593 Hsieh C K & Hsieh H H (1936) Radiology 27, 101 MacCarty C S, Waugh J M & Coventry M B (1961) Surgery, Gynecology and Obstetrics 113, 551-554 Pearhnan A W & Friedman M (1970) American Journal of Roentgenology 108, 333-341 Sennett E J (1953) American Journal of Roentgenology 69, 613-622 Utne & Pugh (1955) American Journal of Roentgenology 74, 593
rheumatic mitral valve disease and had previously been treated for infective endocarditis, due to Streptococcus viridans, in 1953. On admission he was pyrexial (38°C) with splenomegaly, and gave a history of night sweats and Weight loss. His hemoglobin fell from 11.5 to 9.7 %. Seven successive blood cultures grew a diphtheroid species, which was also grown from skin swab cultures. The organism was identified by the National Collection of Type Cul-tures at Colindale as a lactobacillus, and dismissed as a contaminant. Multiple investigations (see Table 1) to find an alternative etiology were undertaken, but all proved negative. Eventually laparotomy was performed, proceeding to splenectomy, in the expecLactobacillus Infective Endocarditis tation of finding a lymphoma. David Isenberg MRCP Histology, however, showed a normal spleen (for A B S Mitchell MRCP) apart from one infarct (Fig 1). A postoperative (St Ann's Hospital, Tottenham, London N15) urinary tract infection was treated with a two-week course of ampicillin. A S, man aged 50 His pyrexia and night sweats settled and he was This patient, who worked as a clerical officer for the Post Office, was admitted into the Prince of discharged; remaining well until early 1976, when Wales's Hospital in November 1974 with suspected infective endocarditis. He was known to have Table 2 Classification of lactobacilli (Bergey 1957) (1) Homofermentative (producing lactic acid only from glucose) (2) Heterofermentative (producing other end-products such as CO2, alcohol and acetic acid, besides lactic acid, from glucose)
Fig 1 Splenic infraction (small circle shown is an artifact)
Optimum temperature 37-60C L. caucalasicus L. lactis L. helveticus L. acidophilus L. bifidus L. bulgarius L. delbrueckii
Optimum temperature 28-320C L. pastorianus
Optimum temperature 28-320C L. casei L. Ieichannii L. plantarum
Optimum temperature 35-40°C L. fermenti
L. buchner L. brevis
279
Clinical Section
his nights sweats recurred. He was admitted to St Ann's Hospital in April 1976 after the sudden onset of sensory dysphasia, which was followed whilst he was in the ward by two Jacksonian-type epileptic fits. Carotid angiography and EEG on this occasion showed that he had had a left
temporoparietal infarct. He was again pyrexial, and blood and skin swab cultures again grew lactobacilli. On this occasion they were differentiated by varying rates of growth and sensitivities. He was treated for infective endocarditis with penicillin G, 12 megaunits i.m. daily, streptomycin
Fig 2 Lactobacillus casei var. rhamnosus,from blood culture ( x 1000)
Table 3 Tabulated details of case reports of Lactobacillus Infective Endocarditis Country of
Duration of symptoms before
admission I month
Dental disease
Prior cardiac history Acute rheumatic fever
M
I month
F
2 months
High blood pressure with enlarged heart Acute rheumatic fever with aortic and mitral disease
64
M
3 months
Abscess drained 3 months earlier 'Granulomatous' teeth extracted 2 months earlier Poor teeth
34
F
I month
England 1964
31
M
2 weeks
No, but parturition 5 weeks earlier Poor teeth which later required extraction
Acute rheumatic fever with mitral stenosis and aortic incompetence Acute rheumatic fever followed by mitral incompetence
France 1969
9
M
3 months
No, but tonsillectomy prior to relapse
Ventricular septal defect
Canada 1970 America 1973 England 1973
36
F
2 weeks
44
F
3 weeks
62
M
3 months
Tenenbaum & Warner
America
63
M
10 months
(This case)
England 1975
60
M
4 weeks
Age 21
Sex F
42
32
Germany 1955 France 1963
National Collection of Type Cultures (NCTCm) Horeau et al. NCTC
Authors Marschall Biocca & Reitano Biocca &
Seppilli Dietzsch Jeandet
Axelrod et al. NCTC
origin
Germany 1938 Brazil 1943 Brazil 1947
1975
Scaling procedure 3 weeks earlier Teeth extracted just prior to onset of symptoms Severe tooth decay Poor teeth, subsequently extracted
* Extension of table by Axelrod et al. (1973) * Case reports and personal communications
Aortic coarctation resected age 27; aortic aneurysm resected age 29 None Mitral valve disease and atrial fibrillation present for at least 5 years
Acute rheumatic fever. Previous infective endocarditis due to Streptococcus viridans
280
Proc. roy. Soc. Med. Volume 70 April 1977
500 mg i.m. daily and probenecid 500 mg orally twice daily. His pyrexia and night sweats settled and his white cell count, 20 000/mm3 on admission, returned to normal. Further epileptic fits in September 1976 have warranted his starting long term anticonvulsants.
Discussion It seems certain that the cause of this patient's pyrexia in November 1974 was the same as that in April 1976: a lactobacillus infective endocarditis. On the first occasion this was partially, albeit
inadvertently, treated by the surgical houseman
Table 4 Details of Lactobacilius Infective Endocarditis case reports-continued
Back pain No No No No No No No
Mitral
ArthraYgia
Dietzsch Jeandet
No
NCTC Horeau et al. NCTC Axelrod et al. NCTC Tenenbaum & Warner (This case)
Valvular
involvement Mitral Aortic Aortic and mitral Mitral Aortic and mitral Mitral No No Mitral Mitral Mitral
Authors Marschall Biocca & Reitano Biocca & Seppilli
Yes Yes
No
Enlarged spleen
Fever Anemia
0C(OF)
? Yes Yes
Yes 40 (104) 39.4 (103)
Cerebral Right femoral
Yes Yes
38.9 (102) 39.8 (103.6)
No No No Yes No No
No No No No Retinal No
No Yes ? Yes Yes Yes
99 (one occasion only) 40 (104) Yes 39.4 (103) 38.9 (102) No
Yes
Cerebral splenic
Yes
38.0 (100.5)
Emboli Cerebral Cerebral No
No No
Yes
Table S Details of Lactobacillus Infective Endocarditis case reports-continued Authors Marschall Biocca & Reitano
Biocca & Seppilli Dietzsch Jeandet NCTC Horeau et al.
Positive blood cultures I Ante mortem I Post mortem 8 (L. acidophilus)
Duration outcome of illness 1 month/fatal
2 (L. acidophilus) 4 (L. casei); first 8 all negative 5 (initial cultures were negative) 3 (L. case!) 1 (2 negative)
3 months/fatal 8 months/fatal
3 months/fatal
3 months/survived 7 weeks/survived 6 weeks/survived but later relapsed
3 with recurrence
6 weeks/survived Survived
Axelrod et al.
7 out of 8 grew L. casei 9 (L. plantarum)
9 weeks/survived
NCTC
10 (L. case!)
4 months/survived
9 out of 12 L. casei
NCTC
Tenenbaum & Warner
grew
(This case)
7 initially grew L. cavei
5 months/survived but then relapsed 3 months/survived 3 months/survived but later relapsed
6 with recurrence
Survived
Treatment None
Sulphonamides for at least I week; sodium iodide for 5 days Sulphonamides for uncertain time Penicillin (up to 20 M. units i.v. for 8 weeks)+streptomycin 1.5 G i.m. for 9 weeks Penicillin (40 M. units i.v.); tetracycline 2 g orally; streptomycin I g i.m. for 5j weeks Erythromycin 2 g daily for 5 weeks Penicillin (up to 2.4 M. units i.m. for 6 weeks); sulphonamide (5 g daily for 6 weeks) + chloramphenicol (3 g daily for previous 10 days) 'Massive' antibiotic therapy with penicillin streptomycin and sulphonamide Cephaloridine (dose not known) Penicillin (up to 48 M. units i.v. for 3 weeks) + ampicillin (6 g i.m. for 2 weeks) Penicillin (up to 40 M. units daily); streptomycin I g daily + lincomycin. Neutropenia occurred and gentamicin and ampicillin were substituted Cephalothin 6 g daily for 7 days, 4 g for
26 days By accident ampicillin 1 g daily for 2 weeks. With recurrence, initially given erythromycin 2 g daily, then penicillin 12 M. units i.m. + streptomycin I g i.m. daily for 6 weeks
Clinical Section
prescribing a two-week course of ampicillin, postoperatively, for a urinary tract infection. The lactobacillus is not normally considered a pathogen except in its long accepted role in the wtiology of dental caries (Wilson & Miles 1975). Lactobacilli (Fig 2) are gram-positive rods, typically nonmotile and not producing spores. They are not acid fast but are wrobic and facultatively anmrobic. Many species grow better at a low oxygen tension, i.e. they are micro2rophilic. They grow best at about pH 6, but may be difficult to grow in vitro and require special culture media. A recent classification is shown in Table 2. Their bestknown function is the supplementing of host defences in the vagina, where they produce acid conditions unfavourable to many of the common pathogenic bacteria. Evidence for the pathogenicity of lactobacilli does however exist, both in animals and man. In 1930 Howitt and Van Meter produced joint lesions in rabbits by intravenous injections of living aciduric lactobacilli of both dental and intestinal origin. Sims in 1964 described a mucoid mutant of Lactobacillus casei that was pathogenic to mice and rats. In 1965 Rosan and Hammond showed that a capsulated variant of a strain of Lactobacillus casei had enhanced virulence in rabbits compared with a noncapsulated variant. There have been isolated reports of human endocarditis, septicmmia and meningitis, and it is the first of these three which I have collected and tabulated. These cases have been collected from the world literature (notably from the paper by Axelrod et al. 1973) and case reports sent to the National Collection of Type Cultures (Tables 3-5). The various symptoms shown in Tables 3-5 do not indicate any obvious features distinguishing the endocarditis in these patients from that due to more usual organisms (see for example Cates and Christie 1951). The first four patients described were all affected before the introduction of penicillin and they all died. The last eight patients have survived, though in three cases after relapses. No standard method of treatment has emerged, though penicillin and streptomycin, sometimes in very large doses, have proved successful in several cases. Hayward (1973) said that 'in spite of improved and more elaborate bacteriological techniques', in 30% of cases of infective endocarditis positive blood cultures are still not obtained. In conclusion,
281
it is tempting to suggest, that part of the explanation may lie with the lactobacillus, an organism difficult to grow in vitro and easy to dismiss as a contaminant.
Acknowledgment: I am grateful to DrA B S Mitchell for his encouragement and to Mrs P Gibson, Dr J A F McLean and Mr E Everest for technical assistance. REFERENCES Axelrod J, Keuseb G T et al. (1973) Annals of Internal Medicine 78, 33-37 Buchanan R E & Gibbons N E (eds) (1957) Bergey's Manual of Determinative Bacteriology, 7th ed. Williams & Wilkins, Baltimore Biocca E & Reitano D (1943) Arquivos de biologia, 27, 114-120 Biocca E & Seppifli A (1947) Journal ofInfectious Disease 81, 112-115 Cates J E & Christie R V (1951) Quarterly Journal of Medicine 20, 93-130 Dietzsch H L (1955) Monatsschrift fur Kinderheilkunde 103, 240-243 Hayward G W (1973) British Medical Journal ii, 708 Horeau J, Nicolas G, Courtieux A et al. (1969) Annales de medicine interne 120, 125-129 Howitt B & Van Meter M (1930) Journal of Infectious Diseases 46, 368 Jeandet J C (1963) MD Thesis, Paris. Editions AGEMP, Paris Marseball F (1938) Zentralblatt fur Bakteriologie 141, 153 Rosan B & Hammond B F (1965) Journal of Dental Research 44, 783 Sims W (1964) Journal ofPathology and Bacteriology 87, 99 Tenenbaum M J & Warner J F (1975) Annals ofInternal Medicine 82, 4 Wilson G S & Miles A A (1975) Topley and Wilson's Principles of Bacteriology and Immunity, 6th ed. Edward Arnold, London
The following cases were also presented: Idiopathic Orthostatic Hypotension Treated with Dihydroergotamine Dr S Winner (for Dr B I Hoffbrand) (Whittington Hospital, London N19) Bacteroides Septicemia following Anorectal Sepsis Mr G Sagor (for Mr Adam Lewis) (Royal Free Hospital, Pond Street, London NW3 2QG) Ankylosing Spondylitis and Pulmonary Fibrosis Dr A M Silas (for Dr A G White) (Whittington Hospital, London N19) Chronic Cervical Syphilitic Meningomyelitis Dr R J Greenwood (for Dr M Harington) (St Charles's Hospital, London WJO)