ZYGOMYCETIC GANGRENOUS CELLULITIS

ZYGOMYCETIC GANGRENOUS CELLULITIS

1337 0 Type IY E3 Type I DtMPUOOuU . Retinal Extract + The reaction ceased when vancomycin was stopped, recurred on re-challenge, and was succ...

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1337

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The reaction ceased when vancomycin was stopped, recurred on re-challenge, and was successfully treated with corticosteroid eyedrops. The patients’ eosinophil count increased to 58 % during treatment (6-3 x 109 1). There were no other features of a hypersensitivity or other reaction. The septic arthritis responded

favourably to therapy. Although this side-effect had some features of a dose-related toxic response we feel an allergic reaction is likely, bearing in mind the response to corticosteroids and especially the eosinophilia. Allergic reactions to vancomycin are not rare and are potentially serious, leading in some cases to discontinuation of therapy. Our experience suggests that vancomycin-associated lacrimation may be controlled by local steroids and essential therapy may be continued.

Dr Steevens’ Hospital and Trinity College Medical Dublin 8, Ireland 1.

Fig 2-Inhibition of endothelial collagenolysis by DIMP. with normal and benign breast tissues, a 2-5 fold decrease (p < 0-01) in capillary number/mm2 was present in desmoplastic (scirrhous) carcinomas (table). Furthermore, DIMP significantly abolished (p < 002) endothelial collagenolysis (fig 2); DIMP exerted no effect on endothelial viability, [3H]thymidine uptake, or attachment. Since most tumours would be expected to stimulate angiogenesis via the release of endothelial growth and chemotactic factors and therefore manifest increased numbers of capillaries, the decrease in capillary number in desmoplastic breast carcinoma suggests an anti-angiogenesis function for the desmoplastic response. Furthermore, the ability of DIMP to abolish endothelial collagenolysis during in-vitro endothelial chemotaxis may represent the mechanism by which the desmoplastic response exerts its anti-angiogenesis function in vivo.

Supported by US Public Health

Service grant CA 40225.

Department of Pathology, UCLA School of Medicine,

Los

Angeles, California 90024, USA

SANFORD H. BARSKY L. LEE NELSON VERONICA A. LEVY

Increased invasion and spontaneous metastasis of BL6 melanoma with inhibition of the desmoplastic response m C57 BL6 mice Cancer Res 1987, 47: 1663-67. 2. Barsky SH, Gopalakrishna R. High metalloproteinase inhibitor content of human cirrhosis and its possible conference of metastasis resistance. JNCI (in press) 3 Folkman J. How is blood vessel growth regulated in normal and neoplastic tissue? G. H. A. Clowes memorial award lecture. Cancer Res 1986; 46: 467-73 4 Kalebic T, Garbisa S, Glaser B, Liotta LA. Basement membrane collagen Degradation by migrating endothelial cells. Science 1983, 221: 281-83. 1

Barsky SH, Gopalakrishna R.

VANCOMYCIN-ASSOCIATED LACRIMATION

SIR,—Vancomycin is widely used in Dublin hospitals because of high incidence of infection with methicillin-resistant Staphylococcus aureus. It is a toxic drug, its main side-effects being nephrotoxicity, proteinuria, ototoxicity, tinnitus, neutropenia, thrombophlebitis, and allergic reactions. The "red man’s syndrome" (hypotension and maculopapular rash on the upper part of the body) is associated with the rapid administration of vancomycin and is thought to be mediated through a histaminergic response.’ We report another adverse effect of vancomycin. A 49-year-old man with rheumatoid arthritis and normal renal function was treated with intravenous vancomycin for septic arthritis of his second right metatarsophalangeal joint, caused by Staph aureus resistant to other antibiotics. The patient had profuse tears within two days of starting treatment. The reaction began within 1 h of starting a 75-minute infusion of vancomycin (750 mg twice a day), reached a peak after 2 h, and continued for up to 10 h. There was associated conjunctivitis but no rash, and vital signs the

DAVID TEMPERLEY EOIN CASEY ROISIN CONNOLLY SUSAN FITZSIMON ERIC MULVIHULL JOHN FEELY

School,

Garrelts JC, Peterie JD. Vancomycm and the

"red man’s

syndrome". N Engl J Med

1985;312: 245.

ZYGOMYCETIC GANGRENOUS CELLULITIS

SiR,—We report a case of gangrenous cellulitis caused by the rare saprophytic zygomycete Saksenaea vaszformis’ secondary to a compound fracture. A 55-year-old woman fell from the fourth floor of an hotel in Spain and sustained multiple injuries which included a compound supracondylar fracture of the left knee. The fracture was reduced and the wound sutured, but no formal debridement of the wound was done and no prophylactic antibiotics were given. 4 days later she was transferred to Newcastle upon Tyne by air ambulance, by which time the wound was inflamed and gangrenous. Two debridements involving removal of necrotic skin, subcutaneous tissue, and muscle to the level of the bone were done during the next 10 days. Microbiological cultures of wound swabs and blood cultures were negative. The patient remained pyrexial and her condition deteriorated while the lesion failed to improve despite high-dose broad-spectrum antibiotic treatment. 14 days after the accident, examination of the now 50 cm ulcer showed a covering of white fibres at the wound edge, especially in the adipose tissue (figure). A biopsy specimen revealed the fibres to be fungal elements and intravenous amphotericin was started. S vasiformis was cultured from this specimen. The lesion continued to extend and histological examination of biopsy specimens from above the ulcer revealed invasion of blood-vessels by fungal hyphae. The affected leg was amputated at the hip as a life-saving measure. The patient improved rapidly after this operation and the stump appeared free of infection at 5-week follow-up, by which time she had received a total of 2gof amphotericin B. Zygomycetes are opportunistic fungal pathogens which may cause fatal invasive rhinocerebral, pulmonary, or disseminated infections, especially in patients with impaired host defences from causes including malignancy, immunosuppressive therapy, and

including blood pressure did not alter.

The reaction occurred after all doses of vancomycin (even after the dose was reduced to 500 mg) and when plasma levels were within the therapeutic range, although the reaction was stronger when levels were above this range. Patient-blinded placebo administration did not lead to lacrimation.

White fibres at wound edge.

1338 diabetes mellitusZygomycosis is also an unusual cause of gangrenous cellulitis associated with surgical, traumatic, or burn wounds.3 The genera Rhizopus, Mucor, Basidiobolus, and Absidia are often reported as pathogenic in this situation, while there have been only two reports of infection caused by S vasiformis.4,S This case illustrates the potential for fulminating gangrenous cellulitis to develop after inadequate surgical debridement of compound fractures. Zygomycetic infection should be included in the differential diagnosis of necrotising skin and soft-tissue infection, especially when these fail to respond to adequate conventional antibacterial therapy. This case also illustrates that microbiological investigation of surface swabs may be inadequate and that microscopy and culture of excised necrotic tissue is necessary for the diagnosis. Without such an approach this type of zygomycete infection may be overlooked and life-saving treatment with radical debridement combined with antifungal drugs may be

delayed. We thank Prof D. W. R. Mackenzie of the P.H.L.S. mycology reference laboratory and Dr R. J. Hay, St Johns Hospital for Diseases of the Skin, London, for help in identification of the organism and advice on management.

Department of Microbiology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP Department of Microbiology, University of Newcastle Medical School, Newcastle upon Tyne Department of Orthopaedics, Royal Victoria Infirmary, Newcastle upon Tyne 1. Saksena SB. A new genus of the Mucorales. 2. Marchevsky AM, Bottone EJ, Geller SA,

D. G. NEWELL M. J. HUDSON A. BASKERVILLE

PHLS Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wiltshire SP4 0JG

1. Newell DG, Baskerville A. Experimental and natural Campylobacter pylori infections in the Rhesus monkey. In Proc IVth Int Workshop Campylobacter Infections (in

press) 2. Baskerville A, Newell DG Chronic

pylori dis infection

a

gastritis in the Rhesus monkey associated with C histological study of the natural and expenmental disease. J

Pathol 1987; 152: 229. 3. Baskerville A, Newell DG.

Naturally occurring chronic gastritis and C pylori infection the Rhesus monkey: a potential model for gastritis in man Gut (in press). 4. Hudson MJ, Bhavsar P, Wait R. Chemotaxonomy of the Campylobacters. In Proc IVth Int Workshop Campylobacter Infections (in press). 5. Bronsdon MA, Schoenknecht FD. Pyloric campylobacter isolated from non-human primate stomach In: Proc IVth Int Workshop Campylobacter Infections (in in

6.

press) Curry A, Jones DM, Eldndge J. Sprial organisms in the baboon stomach. Lancet 1987; ii:634-35

C. CEFAI SHUNT TREATMENT FOR FETAL OBSTRUCTIVE UROPATHY T. S.

J. ELLIOTT

R. W. NUTTON A. E. LOCKETT

J. POOLEY Mycologia 1953, 45: 426-36. Giger DK. The changing spectrum of

disease, etiology and diagnosis of mucormycosis. Hum Pathol 1981; 11: 457-63. G, Foley FD, et al. Opportunistic infection of the burn wound with phycomycetes and Aspergillus. Arch Surg 1971; 102:476-82. 4. Ajello L, Dean DF, Irwm RS. The zygomycete Saksenaea vasiformis as a pathogen of humans with a critical review of the etiology of mucormycosis. Mycologia 1953; 45: 3. Bruck HM, Nash

426-36. 5

from the primates Macaca nemestrma5 and baboon,6 the rhesus monkey appears to be the only animal, apart from man, in which naturally occurring gastritis has been associated with C pylori. As we have suggested,1.3 this infection in the rhesus monkey could be useful as a model of the human disease.

Hay RJ, Campbell CK, Marshall WM, Rees BI, Pincott J Disseminated zygomycosis (mucormycosis) caused by Saksenaea vasiformis. J Infect 1983; 7: 162-65.

NATURALLY OCCURRING GASTRITIS ASSOCIATED WITH CAMPYLOBACTER PYLORI INFECTION IN THE RHESUS MONKEY

SIR,-Contrary to the statements of Dr Berkowitcz and Dr Lee and Dr Mitchell and colleagues (Sept 19, p 680 and 681) that Campylobacter pylori has not been isolated from any animal species other than man, we have isolated campylobacter-like organisms (CLO) from the gastric mucosa of Rhesus monkeys at necropsy. I" Most of these animals had histological evidence of chronic gastritis, namely mild to heavy infiltration of the lamina propria of the antrum by lymphocytes, plasma cells, and histiocytes.2.3 Electron microscopy showed that in all cases this gastritis was accompanied by CLO in the lumen in intimate association with the apical plasma-cell membrane of gastric epithelial cells.3 The CLO isolates obtained from the monkeys were morphologically identical to C pylori, with multiple sheathed unipolar flagella. Biochemically these organisms were catalase and oxidase positive and produced large quantities of urease. The fatty acid methyl ester profiles, analysed by gas-liquid chromatography and mass spectrometry, were characteristic of C pylori. The protein antigen profiles, detected by western blotting with rabbit anti-C pylori and anti-C jejuni antisera, and the C pylori species-specific monoclonal antibody, CP 1, were also identical with C pylori strains. By all criteria the isolates from these Rhesus monkeys were characterised as C pylori. C pylori has, therefore, been isolated from a site other than the human gastric mucosa and a natural animal infection has now been found. Moreover the lesions associated with infection in the rhesus monkey are similar to those of chronic gastritis in man. It is possible that these animals acquired their infection from their frequent, though obviously not close, contact with their handlers during captivity. However, the chance of a common environmental source cannot be excluded at this stage. Although there have been previous reports of the isolation of CLOs, both morphologically and biochemically similar to C pylori,

!R,—retat

obstructive

uropathy

in

the

presence

of

oligohydramnios carries a very poor prognosis.1 Vesicoamniotic shunting is aimed at preventing progressive renal damage by decompressing the bladder2.3and reducing the risk of lung hypoplasia by restoring liquor volume.’ Despite some technical successes, the results of shunting given by the International Fetal Surgery Registry5 and reviewed by Dr Elder and colleagues (Oct 31, p 1007) are disappointing, with a perinatal mortality rate of 48-67%. Patient selection for shunting is crucial and fetuses with other abnormalities, with abnormal karyotypes, and with irreversible renal damage should be excluded.6 Several workers emphasise a role for ultrasound-guided bladder needling and urinary electrolytes in deciding management, a urinary sodium above about 100 mmol/1 being widely accepted as an indicator of poor renal function, suggesting dysplasia.v-9 Bladder urine is a mixture of urine from both kidneys, which need not be symmetrically affected by dysplasia. We report a successful case of shunting in which urine was selectively sampled from the bladder and both kidneys. The results indicated adequate renal function on one side, despite bladder electrolytes compatible with irreversible renal damage. The patient was referred at 23 weeks with anhydramnios, bilateral moderate hydronephrosis/hydroureter, and an enlarged bladder and proximal urethra. There were no other abnormalities and fetal blood sampling revealed a 46,XY karyotype. Biochemical tests on urine obtained by ultrasound-guided needling of bladder and the renal pelvis of both kidneys (table) suggested adequate left kidney function. One week later, repeat sampling confirmed these findings but showed possible deterioration of the left kidney (a rise **

in

sodium).

A non-valved double pigtail plastic vesicoamniotic shunt (Rocket) was inserted percutaneously. The bladder drained and liquor gradually reaccumulated. The right hydronephrosis disappeared, while mild left hydronephrosis/hydroureter persisted. Repeat left-sided sampling at 28 and 32 weeks confirmed satisfactory renal function (falling sodium). Normal growth, umbilical artery Doppler wave-forms, and fetal breathing movements were observed. A 3.3 kg infant, delivered vaginally in good condition at 36 weeks, did not require ventilation or supplementary oxygen. A catheter cystogram demonstrated right vesicoureteric reflux and a much dilated posterior urethra. After shunt removal on day 7, hook diathermy of urethral valves resulted in a normal stream. Serum creatinine fell below 100 jmol/1. After an Escherichia coli urinary tract infection and septicaemia a micturating cystourethrogram was done revealing incomplete resection of valves and persistent right-sided reflux. Scintigraphy showed no renal function on the right. Repeat valve resection and right nephroureterectomy were