925
Outbreaks of multiresistant Haemophilus influenzae infection SIR,-Dr Sturm and colleagues (Jan 27, p 214) report an outbreak multiresistant non-encapsulated Haemophilis influenzae infections among patients in a pulmonary rehabilitation centre in of
separation of those with other respiratory infections, exclusion of staff with respiratory infections, and more diligent hygiene procedures might reduce the extent of such an outbreak. This approach is impracticable because of restricted amenities in the present economic climate. G. M. SCOTT R. THOMSON M. P. REBEC C. C. KIBBLER M. D. SMITH J. HOLTON
Holland. We are investigating a similar outbreak on acute admission wards of a teaching hospital, with evidence of spread to two other
hospitals in the district. The first isolate was from a sputum sample obtained from a patient on ward A on Jan 9, 1990. Organisms with the same sensitivity pattern were cultured from sputa collected over the next 8 days from a further four patients on ward A. One further patient nursed on ward A was transferred to a care-of-the-elderly unit (ward B) in another hospital on Jan 8 and her sputum taken on Jan 13 proved positive. On ward B, sputum from another patient taken on Jan 22 was positive. Another patient from another ward (C) in the main hospital provided positive sputum on Jan 12. One of the index cases on ward A had been on ward C until mid-December and although these wards are geographically close, no other infected patient or carrier could be found to account from this crossinfection. All these patients from whom sputum was obtained were frail ellerly women (age range 72-92 years), most of who had mild chronic respiratory disease and had new non-specific respiratory symptoms, including productive cough with malaise and fever after admission. Three patients died, 3, 6, and 16 days after a positive sputum had been obtained. In two of these (and in one other),
different strains of Branhamella catarrhalis in addition to H influenzae were found in the sputum. Screening of patients and staff by throat and high nose swabs was undertaken every week from Jan 17. Four patients (out of eighteen) and three staff members on ward A, one patient on ward B, and one patient on ward D (also close to wards A and C) proved to be carriers. Virtually all staff members and most patients had had acute upper respiratory tract infections during January. All the isolates were indistinguishable: they were non-encapsulated H influenzae biotype 3," and produced B-lactamase (by nitrocefin colour change) and chloramphenicol acetyltransferase.2 Antibiotic sensitivities were done by disc diffusion and minimum inhibitory concentrations (MICs) were measured by the agar dilution method on ’Isosensitest’ agar with 5% lysed horse blood with inocula of 104 and 105 colony-forming units. All isolates were resistant to amoxycillin (MIC 4-16 mg/1), tetracycline (16-32), sulphamethoxazole (32-64), and chloramphenicol (4-16). They were sensitive to rifampicin (0-25), cefuroxime (0-5-1-0), trimethoprim (less than 0-03), and ciprofloxacin (less than 0.03). Resistance could be transferred from 14 of 21 outbreak strains to a recA recipient strain of H influenzae. Agarose gel electrophoresis3 failed to show a plasmid in each of the original isolates, but a 45MD plasmid has been demonstrated in six transconjugant strains studied so far. Preliminary work shows that outer membrane protein profiles are identical. A single dose of 500 mg ciprofloxacin given to two staff members failed to eradicate the organism. However, follow-up screening of patients and staff showed that the organism became undetectable spontaneously within 2 weeks. No carriers were found on the outbreak ward on Feb 9. However, an elderly man with severe chronic obstructive airways disease was admitted from home to another hospital in the district on Feb 5 and sputum taken on Feb 8 was positive for H influenzae that was indistinguishable from the outbreak strain. This outbreak shows that H infuenzae may spread among patients and staff in open general medical wards especially during a period of high prevalence of presumed viral respiratory infections. This event is probably not uncommon but would not usually be recognised unless, as here, the organism had particular characteristics. The morbidity associated with this infection was high and three of fourteen infected or colonised patients died. The organism spread beyond the confines of the outbreak ward either because patients were transferred or it was transmitted by unidentified intermediate carriers. There are no isolation facilities sufficient to cope with this type of outbreak. However, strict infection control measures with cohort nursing of infected patients,
Infection Control Team, Clinical Microbiology, Bloomsbury Health District, London WC1 E 6AU, UK
1. Kilian M. A taxonomic study of the genus Haemophilus with proposal of a new species.
J Gen Microbiol 1976; 93: 9-62. 2. Slack MBE, Wheldon BD, Turk DC. Rapid detection of chloramphenicol resistance in Haemophilus influenzae. Lancet 1977; ii: 1366. 3. Kado CI, Liu S-T. Rapid procedure for detection and isolation of large and small
plasmids. J Bacteriol 1981; 145:
1365-73.
Screening for cystic fibrosis:
use
of
&Dgr;F508
mutation SIR,-Neonatal screening for cystic fibrosis (CF) remains a subject of some debate." Measurement of immunoreactive trypsin (IRT) in blood collected on day 4 is followed by a repeat test (generally at about day 28) in those with the highest IRT concentrations, followed by a sweat test on those with persistently high IRT values. Most groups have found it necessary to do between 8 and 20 second blood tests and 2 or 3 sweat tests per case detected to achieve a final sensitivity of 90-95%. The anxiety induced in parents of babies with false-positive results is a serious problem with this screening programme.
The LiF 508 mutation is present in 45-75 % of CF genes5-7 in most European derived populations and is easily detected by polymerase chain reaction methods, which can easily handle 10 to 20 samples a week. It would, therefore, be possible to replace the second blood test by a direct test for this mutation in the dried blood spot available from the babies with This procedure will
Flow chart
an
initial IRT result above the usual cut-off.
identify: (a) babies homozygous for LiF 508’
comparing present and proposed strategies.
The reduction in sensitivity from 90-95% to 85-95% seems an acceptable price to pay for the elimination of anxiety-provoking second IRT test, and we are proceeding with pilot programmes. With either strategy paediatricians need to remain alert to the possibility of CF in babies with relevant symptoms but a negative screening test. Sensitivity of the new strategy should improve if other frequent mutations are detected, permitting a cocktail of primers to be used to test for multiple mutations. Such knowledge is needed more pressingly in Italy or Spain where &Dgr;F508. is less frequent, and especially in Ashkanazi Jewish populations.
Outbreaks of multiresistant Haemophilus influenzae infection SIR,-Dr Sturm and colleagues (Jan 27, p 214) report an outbreak multiresistant non-encapsulated Haemophilis influenzae infections among patients in a pulmonary rehabilitation centre in of
separation of those with other respiratory infections, exclusion of staff with respiratory infections, and more diligent hygiene procedures might reduce the extent of such an outbreak. This approach is impracticable because of restricted amenities in the present economic climate. G. M. SCOTT R. THOMSON M. P. REBEC C. C. KIBBLER M. D. SMITH J. HOLTON
Holland. We are investigating a similar outbreak on acute admission wards of a teaching hospital, with evidence of spread to two other
hospitals in the district. The first isolate was from a sputum sample obtained from a patient on ward A on Jan 9, 1990. Organisms with the same sensitivity pattern were cultured from sputa collected over the next 8 days from a further four patients on ward A. One further patient nursed on ward A was transferred to a care-of-the-elderly unit (ward B) in another hospital on Jan 8 and her sputum taken on Jan 13 proved positive. On ward B, sputum from another patient taken on Jan 22 was positive. Another patient from another ward (C) in the main hospital provided positive sputum on Jan 12. One of the index cases on ward A had been on ward C until mid-December and although these wards are geographically close, no other infected patient or carrier could be found to account from this crossinfection. All these patients from whom sputum was obtained were frail ellerly women (age range 72-92 years), most of who had mild chronic respiratory disease and had new non-specific respiratory symptoms, including productive cough with malaise and fever after admission. Three patients died, 3, 6, and 16 days after a positive sputum had been obtained. In two of these (and in one other),
different strains of Branhamella catarrhalis in addition to H influenzae were found in the sputum. Screening of patients and staff by throat and high nose swabs was undertaken every week from Jan 17. Four patients (out of eighteen) and three staff members on ward A, one patient on ward B, and one patient on ward D (also close to wards A and C) proved to be carriers. Virtually all staff members and most patients had had acute upper respiratory tract infections during January. All the isolates were indistinguishable: they were non-encapsulated H influenzae biotype 3," and produced B-lactamase (by nitrocefin colour change) and chloramphenicol acetyltransferase.2 Antibiotic sensitivities were done by disc diffusion and minimum inhibitory concentrations (MICs) were measured by the agar dilution method on ’Isosensitest’ agar with 5% lysed horse blood with inocula of 104 and 105 colony-forming units. All isolates were resistant to amoxycillin (MIC 4-16 mg/1), tetracycline (16-32), sulphamethoxazole (32-64), and chloramphenicol (4-16). They were sensitive to rifampicin (0-25), cefuroxime (0-5-1-0), trimethoprim (less than 0-03), and ciprofloxacin (less than 0.03). Resistance could be transferred from 14 of 21 outbreak strains to a recA recipient strain of H influenzae. Agarose gel electrophoresis3 failed to show a plasmid in each of the original isolates, but a 45MD plasmid has been demonstrated in six transconjugant strains studied so far. Preliminary work shows that outer membrane protein profiles are identical. A single dose of 500 mg ciprofloxacin given to two staff members failed to eradicate the organism. However, follow-up screening of patients and staff showed that the organism became undetectable spontaneously within 2 weeks. No carriers were found on the outbreak ward on Feb 9. However, an elderly man with severe chronic obstructive airways disease was admitted from home to another hospital in the district on Feb 5 and sputum taken on Feb 8 was positive for H influenzae that was indistinguishable from the outbreak strain. This outbreak shows that H infuenzae may spread among patients and staff in open general medical wards especially during a period of high prevalence of presumed viral respiratory infections. This event is probably not uncommon but would not usually be recognised unless, as here, the organism had particular characteristics. The morbidity associated with this infection was high and three of fourteen infected or colonised patients died. The organism spread beyond the confines of the outbreak ward either because patients were transferred or it was transmitted by unidentified intermediate carriers. There are no isolation facilities sufficient to cope with this type of outbreak. However, strict infection control measures with cohort nursing of infected patients,
Infection Control Team, Clinical Microbiology, Bloomsbury Health District, London WC1 E 6AU, UK
1. Kilian M. A taxonomic study of the genus Haemophilus with proposal of a new species.
J Gen Microbiol 1976; 93: 9-62. 2. Slack MBE, Wheldon BD, Turk DC. Rapid detection of chloramphenicol resistance in Haemophilus influenzae. Lancet 1977; ii: 1366. 3. Kado CI, Liu S-T. Rapid procedure for detection and isolation of large and small
plasmids. J Bacteriol 1981; 145:
1365-73.
Screening for cystic fibrosis:
use
of
&Dgr;F508
mutation SIR,-Neonatal screening for cystic fibrosis (CF) remains a subject of some debate." Measurement of immunoreactive trypsin (IRT) in blood collected on day 4 is followed by a repeat test (generally at about day 28) in those with the highest IRT concentrations, followed by a sweat test on those with persistently high IRT values. Most groups have found it necessary to do between 8 and 20 second blood tests and 2 or 3 sweat tests per case detected to achieve a final sensitivity of 90-95%. The anxiety induced in parents of babies with false-positive results is a serious problem with this screening programme.
The LiF 508 mutation is present in 45-75 % of CF genes5-7 in most European derived populations and is easily detected by polymerase chain reaction methods, which can easily handle 10 to 20 samples a week. It would, therefore, be possible to replace the second blood test by a direct test for this mutation in the dried blood spot available from the babies with This procedure will
Flow chart
an
initial IRT result above the usual cut-off.
identify: (a) babies homozygous for LiF 508’
comparing present and proposed strategies.
The reduction in sensitivity from 90-95% to 85-95% seems an acceptable price to pay for the elimination of anxiety-provoking second IRT test, and we are proceeding with pilot programmes. With either strategy paediatricians need to remain alert to the possibility of CF in babies with relevant symptoms but a negative screening test. Sensitivity of the new strategy should improve if other frequent mutations are detected, permitting a cocktail of primers to be used to test for multiple mutations. Such knowledge is needed more pressingly in Italy or Spain where &Dgr;F508. is less frequent, and especially in Ashkanazi Jewish populations.
