54
sphenoidal adenomectomy. Complete remission of Cushing’s disease was seen, apart from osteoporosis. The patient resumed work on her farm and was well. She took hydrocortisone (20-30 mg daily) only when she was stressed. In September, 1990, serum cortisol concentration and 24-h urinary17-OHCS excretion were at the lower normal range. We believe that immunosuppression due to endogenous high blood cortisol was the main factor predisposing our patient to altemariosis. This infection is also an occupational hazard in farmers. Mitotane is not an antifungal drug, so we believe that alternarioris resolved because of the inhibitory effect of mitotane on steroidogenesis. A direct action of mitotane on A alternata infection seems
unlikely.
Department of Endocrinology, Centre of Postgraduate Medical Education, 01-809 Warsaw, Poland
A. A. KASPERLIR-ZALUSRA
of
Department Dermatology, Academy of Medicine,
SABINA BIELUŃSKA
Warsaw
1. Aznar R, Margil J, Puig de la Bellacase J, et al Cutaneous alternariosis ketocenazole Lancet 1989, i. 667-68
responding to
Peritonitis due to
vancomycin-resistant Staphylococcus epidermidis
SIR,-Vancomycin and teicoplanin are glycopeptide antibiotics active against most species of gram-positive bacteria. Vancomycin is often the antibiotic of choice for infections due to coagulasenegative staphylococci, especially if the organisms are resistant to methicillin. However, gram-positive bacteria resistant to glycopeptide antibiotics are emerging. We report a case of continuous ambulatory peritoneal dialysis (CAPD) peritonitis due to Staphylococcus epidermidis resistant to vancomycin and teicoplanin. A 51-year-old man, treated with CAPD for end-stage renal failure, presented with symptoms of CAPD peritonitis. He was given intraperitoneal vancomycin (25 mg/1) and gentamicin (4 mg/1). Response was poor, and culture of the CAPD fluid yielded S epidermidis (’API Staph’, BioMerieux, France). The isolate was non-typable with phage (Staphylococcus Reference Laboratory, Public Health Laboratory Service, UK). The organism was also isolated from the Tenchkoff cannula exit site. Initial antimicrobial sensitivity testing by the breakpoint method showed the isolate to be resistant to vancomycin (minimum inhibitory concentration [MIC] >4 mg/1). On subsequent MIC testing the isolate was resistant to vancomycin (MIC = 16 mg/1), > 32 teicoplanin (MIC > 16 mg/1), gentamicin mg/1), tobramycin (MIC 32 mg/1), and trimethoprim (MIC > 8 mg/l, and sensitive to methicillin, erythromycin, fusidic acid, and tetracycline. The MICs for vancomycin and teicoplanin were not affected by presence or absence in the medium (’Isosensitest’ agar) of 2% lysed blood. The patient was started on oral erythromycin and his symptoms resolved slowly. However, he was readmitted 3 weeks later with CAPD peritonitis; cloudy bags yielded vancomycin-resistant S epiderrraidis. Swabs of the nose, axilla, and perineum taken during both admissions failed to grow vancomycinresistant S epidermidis. During the second admission, the Tenchkoff cannula, which was the probable focus of infection, was removed and the patient was started on haemodialysis. The patient had had ten previous episodes in 3 years of CAPD peritonitis caused by coagulase-negative staphylococci. All episodes had been treated with intraperitoneal vancomycin. It is possible that repeated exposure to vancomycin caused emergence of resistance to this antibiotic. Although the genetic and biochemical basis for resistance to vancomycin and teicoplanin in this isolate is not known, it is unlikely to be plasmid-mediated, because plasmids could not be detected by repeated analysis in 0’7-0’8% agarose gels. That the isolate seemed to be sensitive to vancomycin and teicoplanin by Stokes’ methodz (30 µg discs) with NCTC 6571 as control is worrying; this was seen with both isosensitest and ’Diagnostic Sensitivity Test’ agar with and without lysed horse blood. It is possible, therefore, that similar strains might not be
(MIC
detected in laboratories that use only this method for routine testing. 5 µg vancomycin discs gave a zone size of 2 mm for the patient isolate and 5 mm for NCTC 6571, indicating resistance. Vancomycin resistance of the order reported here has been
reported previously in coagulase-negative staphylococci,3,4 although susceptibility to teicoplanin was not determined. Teicoplanin-resistant, vancomycin-susceptible, coagulase-negative staphylococci have also been described,5,6 as has CAPD peritonitis caused by a strain of S haemolyticus that was initially only teicoplanin-resistant (MIC = 16 mg/1) but developed vancomycin resistance (MIC =8 mg/1).’ It is possible that glycopeptideresistant, coagulase-negative staphylococci will be seen with increasing frequency, particularly if such infections are treated with repeated courses of vancomycin. Additionally, the observation of probable cross-colonisation of CAPD patients with ciprofloxacinresistant coagulase-negative staphylococci8 suggests that a similar cross-colonisation might occur with glycopeptide-resistant organisms. Laboratories may need to review methods for testing susceptibility to vancomycin, particularly if they examine specimens from patients exposed to repeated courses of vancomycin. Such strains may be more readily detected by breakpoint testing at 4 mg/1’ or 5 pg vancomycin discs. The poor clinical response to intraperitoneal vancomycin therapy in our patient suggests that low-level resistance is important, even though the therapeutic concentration used (25 mg vancomycin per litre dialysate) exceeded the in-vitro MIC. We thank Dr C. Brown for permission to report on this patient; Dr R. R. and Dr J. F. Richardson for confirming the identity of the isolate; and Ms Marina Warner for the Stokes test.
Marples
Public Health Laboratory, Northern General Hospital, Sheffield
D. SANYAL
Division of Hospital Infection, Central Public Health Laboratory, London NW9 5HT, UK
A. P. JOHNSON R. C. GEORGE B. D. COOKSON
Department of Renal Medicine, Northern General Hospital, Sheffield
A.
J. WILLIAMS
1 Johnson AP, Uttley AHC, Woodford N, George RC. Resistance to vancomycin and teicoplanin an emerging clinical problem Clin Microbiol Rev 1990; 3: 280-91. 2 Stokes EJ, Ridgway GL. Clinical microbiology 6th ed. London Edward Arnold, 1987 204-21. 3 Cherubin CE, Corrado
ML, Sierra MF, et al Susceptibility of gram-positive cocci to antibiotics, including cefotaxime, moxalactam and N-formimidoyl thienamycin Antimicrob Agents Chemother 1981, 20: 553-55. various
CU, Miller H. Clinical and microbiologic aspects of serious infections caused by Staphylococcus epidermidis. ScandJ Infect Dis 1983; 15: 347-60 Arioli V, Pallanza R Teicoplanin-resistant coagulase negative staphylococci Lancet
4. Tuazon 5
1987, i. 39 6 Wilson APR, O’Hare MD,
=
7. 8.
Felmingham D, Gruneberg RN Teicoplanin-resistant coagulase-negative staphylococcus Lancet 1986, ii: 973 Schwalbe RS, Stapleton JT, Gilligan PH Emergence of vancomycin resistance in coagulase-negative staphylococci N Engl J Med 1987; 316: 927-31 Dryden MS, Ludlam HA, Phillips I. 4-Quinolone-resistant staphylococci J Antumcrob Chemother 1990; 26: 448-49
9
Report by a Working Party of the British Society for Antimicrobial Chemotherpay Breakpoints in in-vitro antibiotic sensitivity testing J Antimicrob Chemother 1988, 21: 701-10
Determinants of
pancreatic and pulmonary cystic fibrosis
status of
SIR,-In their study of pancreatic and pulmonary status among siblings with cystic fibrosis (CF), Dr Santis and colleagues (Nov 3, p 1081) conclude that genetic factors are more important than non-genetic factors in the determination of severity of disease in pancreas and lungs, and that the genetic factors are independent of each other. They suggest that genes at loci other than that for the CF transmembrane conductance regulator (CFTR) might be responsible. I feel that there is no need to invoke other genetic contributions, and that Santis et al too readily dismiss the role of "non-genetic" factors, having examined only a few of these. Important determining factors that are difficult to measure include the adequacy of care given in early life, as well as later, and the degree of compliance with treatment regimens. Cross-infection with virulent
sphenoidal adenomectomy. Complete remission of Cushing’s disease was seen, apart from osteoporosis. The patient resumed work on her farm and was well. She took hydrocortisone (20-30 mg daily) only when she was stressed. In September, 1990, serum cortisol concentration and 24-h urinary17-OHCS excretion were at the lower normal range. We believe that immunosuppression due to endogenous high blood cortisol was the main factor predisposing our patient to altemariosis. This infection is also an occupational hazard in farmers. Mitotane is not an antifungal drug, so we believe that alternarioris resolved because of the inhibitory effect of mitotane on steroidogenesis. A direct action of mitotane on A alternata infection seems
unlikely.
Department of Endocrinology, Centre of Postgraduate Medical Education, 01-809 Warsaw, Poland
A. A. KASPERLIR-ZALUSRA
of
Department Dermatology, Academy of Medicine,
SABINA BIELUŃSKA
Warsaw
1. Aznar R, Margil J, Puig de la Bellacase J, et al Cutaneous alternariosis ketocenazole Lancet 1989, i. 667-68
responding to
Peritonitis due to
vancomycin-resistant Staphylococcus epidermidis
SIR,-Vancomycin and teicoplanin are glycopeptide antibiotics active against most species of gram-positive bacteria. Vancomycin is often the antibiotic of choice for infections due to coagulasenegative staphylococci, especially if the organisms are resistant to methicillin. However, gram-positive bacteria resistant to glycopeptide antibiotics are emerging. We report a case of continuous ambulatory peritoneal dialysis (CAPD) peritonitis due to Staphylococcus epidermidis resistant to vancomycin and teicoplanin. A 51-year-old man, treated with CAPD for end-stage renal failure, presented with symptoms of CAPD peritonitis. He was given intraperitoneal vancomycin (25 mg/1) and gentamicin (4 mg/1). Response was poor, and culture of the CAPD fluid yielded S epidermidis (’API Staph’, BioMerieux, France). The isolate was non-typable with phage (Staphylococcus Reference Laboratory, Public Health Laboratory Service, UK). The organism was also isolated from the Tenchkoff cannula exit site. Initial antimicrobial sensitivity testing by the breakpoint method showed the isolate to be resistant to vancomycin (minimum inhibitory concentration [MIC] >4 mg/1). On subsequent MIC testing the isolate was resistant to vancomycin (MIC = 16 mg/1), > 32 teicoplanin (MIC > 16 mg/1), gentamicin mg/1), tobramycin (MIC 32 mg/1), and trimethoprim (MIC > 8 mg/l, and sensitive to methicillin, erythromycin, fusidic acid, and tetracycline. The MICs for vancomycin and teicoplanin were not affected by presence or absence in the medium (’Isosensitest’ agar) of 2% lysed blood. The patient was started on oral erythromycin and his symptoms resolved slowly. However, he was readmitted 3 weeks later with CAPD peritonitis; cloudy bags yielded vancomycin-resistant S epiderrraidis. Swabs of the nose, axilla, and perineum taken during both admissions failed to grow vancomycinresistant S epidermidis. During the second admission, the Tenchkoff cannula, which was the probable focus of infection, was removed and the patient was started on haemodialysis. The patient had had ten previous episodes in 3 years of CAPD peritonitis caused by coagulase-negative staphylococci. All episodes had been treated with intraperitoneal vancomycin. It is possible that repeated exposure to vancomycin caused emergence of resistance to this antibiotic. Although the genetic and biochemical basis for resistance to vancomycin and teicoplanin in this isolate is not known, it is unlikely to be plasmid-mediated, because plasmids could not be detected by repeated analysis in 0’7-0’8% agarose gels. That the isolate seemed to be sensitive to vancomycin and teicoplanin by Stokes’ methodz (30 µg discs) with NCTC 6571 as control is worrying; this was seen with both isosensitest and ’Diagnostic Sensitivity Test’ agar with and without lysed horse blood. It is possible, therefore, that similar strains might not be
(MIC
detected in laboratories that use only this method for routine testing. 5 µg vancomycin discs gave a zone size of 2 mm for the patient isolate and 5 mm for NCTC 6571, indicating resistance. Vancomycin resistance of the order reported here has been
reported previously in coagulase-negative staphylococci,3,4 although susceptibility to teicoplanin was not determined. Teicoplanin-resistant, vancomycin-susceptible, coagulase-negative staphylococci have also been described,5,6 as has CAPD peritonitis caused by a strain of S haemolyticus that was initially only teicoplanin-resistant (MIC = 16 mg/1) but developed vancomycin resistance (MIC =8 mg/1).’ It is possible that glycopeptideresistant, coagulase-negative staphylococci will be seen with increasing frequency, particularly if such infections are treated with repeated courses of vancomycin. Additionally, the observation of probable cross-colonisation of CAPD patients with ciprofloxacinresistant coagulase-negative staphylococci8 suggests that a similar cross-colonisation might occur with glycopeptide-resistant organisms. Laboratories may need to review methods for testing susceptibility to vancomycin, particularly if they examine specimens from patients exposed to repeated courses of vancomycin. Such strains may be more readily detected by breakpoint testing at 4 mg/1’ or 5 pg vancomycin discs. The poor clinical response to intraperitoneal vancomycin therapy in our patient suggests that low-level resistance is important, even though the therapeutic concentration used (25 mg vancomycin per litre dialysate) exceeded the in-vitro MIC. We thank Dr C. Brown for permission to report on this patient; Dr R. R. and Dr J. F. Richardson for confirming the identity of the isolate; and Ms Marina Warner for the Stokes test.
Marples
Public Health Laboratory, Northern General Hospital, Sheffield
D. SANYAL
Division of Hospital Infection, Central Public Health Laboratory, London NW9 5HT, UK
A. P. JOHNSON R. C. GEORGE B. D. COOKSON
Department of Renal Medicine, Northern General Hospital, Sheffield
A.
J. WILLIAMS
1 Johnson AP, Uttley AHC, Woodford N, George RC. Resistance to vancomycin and teicoplanin an emerging clinical problem Clin Microbiol Rev 1990; 3: 280-91. 2 Stokes EJ, Ridgway GL. Clinical microbiology 6th ed. London Edward Arnold, 1987 204-21. 3 Cherubin CE, Corrado
ML, Sierra MF, et al Susceptibility of gram-positive cocci to antibiotics, including cefotaxime, moxalactam and N-formimidoyl thienamycin Antimicrob Agents Chemother 1981, 20: 553-55. various
CU, Miller H. Clinical and microbiologic aspects of serious infections caused by Staphylococcus epidermidis. ScandJ Infect Dis 1983; 15: 347-60 Arioli V, Pallanza R Teicoplanin-resistant coagulase negative staphylococci Lancet
4. Tuazon 5
1987, i. 39 6 Wilson APR, O’Hare MD,
=
7. 8.
Felmingham D, Gruneberg RN Teicoplanin-resistant coagulase-negative staphylococcus Lancet 1986, ii: 973 Schwalbe RS, Stapleton JT, Gilligan PH Emergence of vancomycin resistance in coagulase-negative staphylococci N Engl J Med 1987; 316: 927-31 Dryden MS, Ludlam HA, Phillips I. 4-Quinolone-resistant staphylococci J Antumcrob Chemother 1990; 26: 448-49
9
Report by a Working Party of the British Society for Antimicrobial Chemotherpay Breakpoints in in-vitro antibiotic sensitivity testing J Antimicrob Chemother 1988, 21: 701-10
Determinants of
pancreatic and pulmonary cystic fibrosis
status of
SIR,-In their study of pancreatic and pulmonary status among siblings with cystic fibrosis (CF), Dr Santis and colleagues (Nov 3, p 1081) conclude that genetic factors are more important than non-genetic factors in the determination of severity of disease in pancreas and lungs, and that the genetic factors are independent of each other. They suggest that genes at loci other than that for the CF transmembrane conductance regulator (CFTR) might be responsible. I feel that there is no need to invoke other genetic contributions, and that Santis et al too readily dismiss the role of "non-genetic" factors, having examined only a few of these. Important determining factors that are difficult to measure include the adequacy of care given in early life, as well as later, and the degree of compliance with treatment regimens. Cross-infection with virulent
