- Email: [email protected]
Staphylococci in Wards
LEADING ARTICLES
THE LANCET LONDON
9
MARCH
1963
Staphylococci in Wards RECENT studies have gone some way towards
answering
several important questions about hospital staphylococci. Are all coagulase-positive staphylococci equally dangerous ? If not, how may we recognise those more likely to cause harm ? What are their principal breedingplaces, and how may they be eliminated ? How do they spread, and how may spread be prevented ? Different strains of Staphylococcus aureus now clearly vary in pathogenic activity. The notorious phage-type 80181 strains, described in Australia by ROUNTREE and FREEMANand subsequently in many other countries, provide the most striking example of a strain with exceptional virulence and infectivity.2 Penicillin-resistant staphylococci have predominated in hospitals for over fifteen years; but this property is no longer the hallmark of a hospital staphylococcus since, unfortunately, similar strains have become common outside hospital. Resistance to antibiotics besides penicillin, notably tetracycline, is a striking feature of strains which abound in many surgical wards.3 Most belong to phagegroup III, but type 80/81 members of group I are also common.2 SHOOTER et a1.4reported that, of 186 different types which they isolated in a surgical ward, only 13 caused disease and only 3 types-all multiresistant members of group 111—spread to more than one patient. Strains causing epidemics in maternity wards more often belong to group i and are less often multiresistant.2 The ease with which multiresistant staphylococci spread in surgical wards, causing wound infections and other complications such as postoperative pneumonia, is presumably related to the favourable environment created for them by the use of a variety of antibiotics in the wards. Several observers have recorded a correlation between the amount of cross-infection in wards and the proportion of the patients who receive antibiotics. The frequently proffered advice to exercise discretion in the use of antibiotics is certainly justified, but can anything more be done ? MARY BARBER and her colleagues5 reported a reduction in the numbers of drug-resistant staphylococci in surgical wards after deliberate limitation of antibiotics to certain combinations, as far as possible
excluding penicillin. Admittedly, special hygienic measures which had previously been initiated may have played a part; 1. 2 3 4. 5.
but this result showed what
might
Rountree, P. M., Freeman, B. M. Med. J. Aust. 1955, ii, 157. Williams, R. E. O. Lancet, 1959, i, 190. Alder, V. G., Gillespie, W. A., Thompson, M. E. M. J. Path.
be
Bact.
1955, 70, 503. Shooter, R. A., Smith, M. A., Griffiths, J. D., Brown, M. E. A. Williams, R. E. O., Rippon, J. E., Jevons, M. P. Brit. med. J. 1958, i, 607. Barber, M., Dutton, A. A. C., Beard, M. A., Elmes, P. C., Williams, R. ibid. 1960, i, 11.
537
achieved by a planned antibiotic policy-though it might be difficult to apply such a policy on a wide scale. The substitution of a penicillinase-insensitive penicillin for the benzylpenicillin now commonly used would greatly change the situation; but such a step would not be justified with any of the new penicillins. In contrast to the preponderance of multiresistant staphylococcal infections in their surgical wards, GILLESPIE et al.6 found that wounds infected at operation contained a wider variety of staphylococci, including several fully sensitive strains. Presumably these were derived from recently admitted patients and from theatre personnel as well as from the wards. These workers concluded that suppuration in closed wounds was nearly always attributable to theatre infection, and HOWE and MARSTONcame to the same conclusion. The most likely way of preventing staphylococcal cross-infection would be to eliminate the sources in which they breed; but in practice many sources are difficult to detect. Patients with wound infections and other open lesions are important sources, who should be isolated whenever possible.8 Infections of the chest, skin, and bowel are especially liable to disseminate large numbers of the pathogens.9 WILLIAMS et apo reported that isolation of all patients known to be sources reduced the incidence of cross-infection in a surgical ward to some extent. But, as they point out, the value of isolation is likely to be limited by the presence commonly of other sources, chiefly nasal carriers,11 which are not clinically evident and can be detected only by systematic bacteriological study. Superficial lesions, including bedsores, are also often colonised by staphylococci without evident inflammation, and constitute hidden sources of infection.12 Nasal carriage of hospital staphylococci by patients and staff is usually demonstrated whenever cross-infection is investigated,13 but the part played by the carrier in causing infection in himself and others has been difficult to assess. WILLIAMS et al.1o have provided valuable information. They showed that patients who acquired staphylococci in their noses while in hospital developed staphylococcal wound sepsis five times as often as those who did not, and that nasal carriers were almost as important in generating cross-infection as patients with open lesions. Since isolation of known sources cannot prevent all cross-infection, other methods have been investigated. GILLESPIE et al. 12 working in surgical wards, studied the effect of prophylactic disinfection of patients’ noses and of lesions liable to staphylococcal colonisation. These measures alone were disappointing, but when they were combined with other hygienic precautions (which also were ineffective by themselves) there was a distinct reduction in cross-infection by multiresistant staphy6.
Gillespie, W. A., Alder, V. G., Ayliffe, G. A. J., Bradbeer, J. W.,
Wypkema, W. Lancet, 1959, ii, 781. 7. Howe, C. W., Marston, A. T. Surg. Gynec. Obstet. 1962, 115, 266. 8. Allan Gray, J. D., Chandler, G. N., Roberts, J. G., Lambert, R. A. Lancet, 1962, ii, 1251. 9. Hare, R., Cooke, E. M. Brit. med. J. 1961, ii, 333. 10. Williams, R. E. O., Noble, W. C., Jevons, M. P., Lidwell, O. M., Shooter, R. A., White, R. G., Thom, B. T., Taylor, G. W. ibid. 1962, ii, 275. 11. Green, K. G. Lancet, 1961, ii, 921. 12. Gillespie, W. A., Alder, V. G., Ayliffe, G. A. J., Powell, D. E. B., Wypkema, W. ibid. 1961, i, 1299. 13. Jarvis, A. W., Wigley, R. D. ibid. 1961, ii, 1168.
538
lococci. PHYLLIS ROUNTREE and her colleagues 14 also obtained a reduction of wound infection when a nasal disinfectant cream was used in conjunction with measures aimed at reducing staphylococcal spread. HENDERSON and WILLIAMS 15 reported failure to influence wound infection by means of nasal disinfectant cream alone, though nasal carriage was reduced. WEINSTEIN6 had a similar failure, taking all his cases together; but, among a few patients whom he was able to swab for a second time before operation, those whose nose swabs were converted to negative had less wound infection than those whose swabs stayed positive after treatment. These conflicting reports probably reflect differences in routes of infection, which may vary from ward to ward and from time to time. Apparently no one precaution can be relied on to control staphylococcal cross-infection in surgical patients: a combination of methods, including isolation, is required. The value of disinfecting potential sources is more evident in maternity units."-19 The cross-infecting staphylococci, derived initially from adults, multiply chiefly in carriage sites on the infants’ bodies-notably the umbilical cord stumpy the groin, perineum, and axilla,21 22 and the nose.23 These sites, being mostly superficial, are accessible to disinfectants, and staphylococcal colonisation and sepsis have been much reduced by bathing the infants in dilute solutions of hexachlorophane.24-26 Hexachlorophane powder has also been used successfully, with reduction of skin sepsis in infants and of breast abscesses in mothers. 21 28 Others have reported favourably on the use of nasal disinfectant cream alone 29 or with hexachlorophane powder.30 31 It is therefore well established that the diligent application of simple antiseptic procedures can greatly reduce staphylococcal disease in maternity hospitals. Control of cross-infection by preventing the spread of staphylococci is difficult because the organism may be conveyed by several routes. The hospital blanket has long been regarded as one vehicle which may transfer staphylococci, by contact if not disinfected between successive users, and by contaminating the air with bacteria-laden dust. RUBBO et a1.32 showed that the dispersion of organisms was largely due to friction between counterpane and underlying blanket, and might be reduced by dispensing with counterpanes or by pinning them to the blanket. DAVIS and NOBLE 33 made the interesting observation that most of the bacteria shed by blankets and by carriers were carried on desquamated 14.
15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33.
Rountree, P. M., Loewenthal, J., Tedder, E., Gye, R. Med. J. Aust. 1962, ii, 367. Henderson, R. J., Williams, R. E. O. Brit. med. J. 1961, ii, 330. Weinstein, H. J. New Engl. J. Med. 1959, 260, 1303. Beaven, D. W., Burry, A. F. Lancet, 1956, ii, 211. Beaven, D. W. ibid. 1958, i, 869. Elias-Jones, T. F., Gordon, I., Whittaker, L. ibid. 1961, i, 571. Jellard, J. Brit. med. J. 1957, i, 925. Gillespie, W. A., Simpson, K., Tozer, R. C. Lancet, 1958, ii, 1075. Hurst, V. Pœdiatrics, 1960, 25, 204. Williams, R. E. O. Lancet, 1961, ii, 173. Farquharson, C. D., Penny, S. F., Edwards, H. E., Barr, E. Canad. med. Ass. J. 1952, 67, 247. Baldwin, J. N., Rheins, M. S., Sylvester, R. F., Shaffer, T. E. Amer. J. Dis. Child, 1957, 94, 107. Gluck, L., Wood, H. F. New Engl. J. Med. 1961, 265, 1177. Simpson, K., Tozer, R. C., Gillespie, W. A. Brit. med. J. 1960, i, 315. Hughes, M. H. J. Hyg., Camb. 1961, 59, 419. Jennison, R. F., Komrower, G. M. Brit. med. J. 1961, i, 89. Cope, A., Shooter, R. A., Green, S. M., Noble, W. C. ibid. 1961, ii, 329. Stokes, E. J., Milne, S. E. J. Hyg., Camb. 1962, 60, 209. Rubbo, S. D., Stratford, B. C., Dixson, S. Brit. med. J. 1962, ii, 282. Davis, R. R., Noble, W. C. Lancet, 1962, ii, 1295.
skin-scales and not on textile fibres. But, although bacteria may be spread by bedding, the proportion of the total staphylococcal traffic for which they are responsible is by no means clear. HowE and MARSTON concluded that blankets and other inanimate objects do not play a major part in initiating infection in surgical patients, and WILLIAMS et al.1o observed no reduction of crossinfection after introducing regular disinfection of cotton blankets. On the other hand, ROUNTREE and BEARD3í obtained evidence that in some patients the route of infection is from bedclothes to wound; and GILLESPIE et al. 21 suggested that the disinfection of bedding con. tributed to the reduction of cross-infection which followed their combination of precautions. These discrepancies probably arise from the fact that routes of spread are many, and that the interruption of one, how. ever important, may have little observable effect. Probably, too, the speed with which blankets become recontaminated is such that they must be disinfected very frequently if much benefit is to be obtained. We badly need more investigation of this problem, and of the economics of frequently disinfecting blankets by the several methods now available.35 Without dependable statistics it is impossible to assess the size of the staphylococcal problem or to determine the value of control measures. Insufficient attention has been given to ascertainment of infections, except in the few hospitals where research on cross-infection is pursued. The detection and recording of all infections, trivial and serious, the identification of important sources of cross-infection, the correlation of clinical and laboratory findings, and the supervision of special precautions all take more time than can be spared by busy doctors and nurses. GARDNER et al.36 met these difficulties by appointing a full-time sister to work with their control-of-infection team. This approach might be considered in hospitals where staphylococci are causing serious trouble
Mineral or Matrix ? THE problem of the pathogenesis of osteoporosis continues to exercise clinicians, radiologists, pathologists, and others. First distinguished histologically from osteomalacia by POMMER in 1885,37 it was not clearly defined clinically until ALBRIGHT and his associates reported their first series of cases in 1941.38 ALBRIGHT’S concept that osteoporosis was due to diminished osteoblastic activity or to a primary disorder of the protein matrix of bone was only slowly accepted, but finally became firmly established. As usual, the heterodoxy of yesterday has become the orthodoxy of today, and now it is the challengers of this hypothesis who are regarded as the rebels. But new techniques have appeared which enable widely held views to be put to the test, and the result is controversy where ten years ago there was only dogma. 34. Rountree, P. M., Beard, M. A. J. Hyg., Camb. 1962, 60, 387. 35. The Sterilisation of Hospital Wool Blankets. International Wool Secretariat, London, 1962. A. M. 36. Gardner, N., Stamp, M., Bowgen, J. A., Moore, B. Lancet, 1962, ii, 710. 37. Pommer, G. Rachitis und Osteomalacie. Leipzig, 1885. 38. Albright, F., Smith, P. H., Richardson, A. M. J. Amer. med. Ass. 1941, 116, 2465.
THE LANCET LONDON
9
MARCH
1963
Staphylococci in Wards RECENT studies have gone some way towards
answering
several important questions about hospital staphylococci. Are all coagulase-positive staphylococci equally dangerous ? If not, how may we recognise those more likely to cause harm ? What are their principal breedingplaces, and how may they be eliminated ? How do they spread, and how may spread be prevented ? Different strains of Staphylococcus aureus now clearly vary in pathogenic activity. The notorious phage-type 80181 strains, described in Australia by ROUNTREE and FREEMANand subsequently in many other countries, provide the most striking example of a strain with exceptional virulence and infectivity.2 Penicillin-resistant staphylococci have predominated in hospitals for over fifteen years; but this property is no longer the hallmark of a hospital staphylococcus since, unfortunately, similar strains have become common outside hospital. Resistance to antibiotics besides penicillin, notably tetracycline, is a striking feature of strains which abound in many surgical wards.3 Most belong to phagegroup III, but type 80/81 members of group I are also common.2 SHOOTER et a1.4reported that, of 186 different types which they isolated in a surgical ward, only 13 caused disease and only 3 types-all multiresistant members of group 111—spread to more than one patient. Strains causing epidemics in maternity wards more often belong to group i and are less often multiresistant.2 The ease with which multiresistant staphylococci spread in surgical wards, causing wound infections and other complications such as postoperative pneumonia, is presumably related to the favourable environment created for them by the use of a variety of antibiotics in the wards. Several observers have recorded a correlation between the amount of cross-infection in wards and the proportion of the patients who receive antibiotics. The frequently proffered advice to exercise discretion in the use of antibiotics is certainly justified, but can anything more be done ? MARY BARBER and her colleagues5 reported a reduction in the numbers of drug-resistant staphylococci in surgical wards after deliberate limitation of antibiotics to certain combinations, as far as possible
excluding penicillin. Admittedly, special hygienic measures which had previously been initiated may have played a part; 1. 2 3 4. 5.
but this result showed what
might
Rountree, P. M., Freeman, B. M. Med. J. Aust. 1955, ii, 157. Williams, R. E. O. Lancet, 1959, i, 190. Alder, V. G., Gillespie, W. A., Thompson, M. E. M. J. Path.
be
Bact.
1955, 70, 503. Shooter, R. A., Smith, M. A., Griffiths, J. D., Brown, M. E. A. Williams, R. E. O., Rippon, J. E., Jevons, M. P. Brit. med. J. 1958, i, 607. Barber, M., Dutton, A. A. C., Beard, M. A., Elmes, P. C., Williams, R. ibid. 1960, i, 11.
537
achieved by a planned antibiotic policy-though it might be difficult to apply such a policy on a wide scale. The substitution of a penicillinase-insensitive penicillin for the benzylpenicillin now commonly used would greatly change the situation; but such a step would not be justified with any of the new penicillins. In contrast to the preponderance of multiresistant staphylococcal infections in their surgical wards, GILLESPIE et al.6 found that wounds infected at operation contained a wider variety of staphylococci, including several fully sensitive strains. Presumably these were derived from recently admitted patients and from theatre personnel as well as from the wards. These workers concluded that suppuration in closed wounds was nearly always attributable to theatre infection, and HOWE and MARSTONcame to the same conclusion. The most likely way of preventing staphylococcal cross-infection would be to eliminate the sources in which they breed; but in practice many sources are difficult to detect. Patients with wound infections and other open lesions are important sources, who should be isolated whenever possible.8 Infections of the chest, skin, and bowel are especially liable to disseminate large numbers of the pathogens.9 WILLIAMS et apo reported that isolation of all patients known to be sources reduced the incidence of cross-infection in a surgical ward to some extent. But, as they point out, the value of isolation is likely to be limited by the presence commonly of other sources, chiefly nasal carriers,11 which are not clinically evident and can be detected only by systematic bacteriological study. Superficial lesions, including bedsores, are also often colonised by staphylococci without evident inflammation, and constitute hidden sources of infection.12 Nasal carriage of hospital staphylococci by patients and staff is usually demonstrated whenever cross-infection is investigated,13 but the part played by the carrier in causing infection in himself and others has been difficult to assess. WILLIAMS et al.1o have provided valuable information. They showed that patients who acquired staphylococci in their noses while in hospital developed staphylococcal wound sepsis five times as often as those who did not, and that nasal carriers were almost as important in generating cross-infection as patients with open lesions. Since isolation of known sources cannot prevent all cross-infection, other methods have been investigated. GILLESPIE et al. 12 working in surgical wards, studied the effect of prophylactic disinfection of patients’ noses and of lesions liable to staphylococcal colonisation. These measures alone were disappointing, but when they were combined with other hygienic precautions (which also were ineffective by themselves) there was a distinct reduction in cross-infection by multiresistant staphy6.
Gillespie, W. A., Alder, V. G., Ayliffe, G. A. J., Bradbeer, J. W.,
Wypkema, W. Lancet, 1959, ii, 781. 7. Howe, C. W., Marston, A. T. Surg. Gynec. Obstet. 1962, 115, 266. 8. Allan Gray, J. D., Chandler, G. N., Roberts, J. G., Lambert, R. A. Lancet, 1962, ii, 1251. 9. Hare, R., Cooke, E. M. Brit. med. J. 1961, ii, 333. 10. Williams, R. E. O., Noble, W. C., Jevons, M. P., Lidwell, O. M., Shooter, R. A., White, R. G., Thom, B. T., Taylor, G. W. ibid. 1962, ii, 275. 11. Green, K. G. Lancet, 1961, ii, 921. 12. Gillespie, W. A., Alder, V. G., Ayliffe, G. A. J., Powell, D. E. B., Wypkema, W. ibid. 1961, i, 1299. 13. Jarvis, A. W., Wigley, R. D. ibid. 1961, ii, 1168.
538
lococci. PHYLLIS ROUNTREE and her colleagues 14 also obtained a reduction of wound infection when a nasal disinfectant cream was used in conjunction with measures aimed at reducing staphylococcal spread. HENDERSON and WILLIAMS 15 reported failure to influence wound infection by means of nasal disinfectant cream alone, though nasal carriage was reduced. WEINSTEIN6 had a similar failure, taking all his cases together; but, among a few patients whom he was able to swab for a second time before operation, those whose nose swabs were converted to negative had less wound infection than those whose swabs stayed positive after treatment. These conflicting reports probably reflect differences in routes of infection, which may vary from ward to ward and from time to time. Apparently no one precaution can be relied on to control staphylococcal cross-infection in surgical patients: a combination of methods, including isolation, is required. The value of disinfecting potential sources is more evident in maternity units."-19 The cross-infecting staphylococci, derived initially from adults, multiply chiefly in carriage sites on the infants’ bodies-notably the umbilical cord stumpy the groin, perineum, and axilla,21 22 and the nose.23 These sites, being mostly superficial, are accessible to disinfectants, and staphylococcal colonisation and sepsis have been much reduced by bathing the infants in dilute solutions of hexachlorophane.24-26 Hexachlorophane powder has also been used successfully, with reduction of skin sepsis in infants and of breast abscesses in mothers. 21 28 Others have reported favourably on the use of nasal disinfectant cream alone 29 or with hexachlorophane powder.30 31 It is therefore well established that the diligent application of simple antiseptic procedures can greatly reduce staphylococcal disease in maternity hospitals. Control of cross-infection by preventing the spread of staphylococci is difficult because the organism may be conveyed by several routes. The hospital blanket has long been regarded as one vehicle which may transfer staphylococci, by contact if not disinfected between successive users, and by contaminating the air with bacteria-laden dust. RUBBO et a1.32 showed that the dispersion of organisms was largely due to friction between counterpane and underlying blanket, and might be reduced by dispensing with counterpanes or by pinning them to the blanket. DAVIS and NOBLE 33 made the interesting observation that most of the bacteria shed by blankets and by carriers were carried on desquamated 14.
15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33.
Rountree, P. M., Loewenthal, J., Tedder, E., Gye, R. Med. J. Aust. 1962, ii, 367. Henderson, R. J., Williams, R. E. O. Brit. med. J. 1961, ii, 330. Weinstein, H. J. New Engl. J. Med. 1959, 260, 1303. Beaven, D. W., Burry, A. F. Lancet, 1956, ii, 211. Beaven, D. W. ibid. 1958, i, 869. Elias-Jones, T. F., Gordon, I., Whittaker, L. ibid. 1961, i, 571. Jellard, J. Brit. med. J. 1957, i, 925. Gillespie, W. A., Simpson, K., Tozer, R. C. Lancet, 1958, ii, 1075. Hurst, V. Pœdiatrics, 1960, 25, 204. Williams, R. E. O. Lancet, 1961, ii, 173. Farquharson, C. D., Penny, S. F., Edwards, H. E., Barr, E. Canad. med. Ass. J. 1952, 67, 247. Baldwin, J. N., Rheins, M. S., Sylvester, R. F., Shaffer, T. E. Amer. J. Dis. Child, 1957, 94, 107. Gluck, L., Wood, H. F. New Engl. J. Med. 1961, 265, 1177. Simpson, K., Tozer, R. C., Gillespie, W. A. Brit. med. J. 1960, i, 315. Hughes, M. H. J. Hyg., Camb. 1961, 59, 419. Jennison, R. F., Komrower, G. M. Brit. med. J. 1961, i, 89. Cope, A., Shooter, R. A., Green, S. M., Noble, W. C. ibid. 1961, ii, 329. Stokes, E. J., Milne, S. E. J. Hyg., Camb. 1962, 60, 209. Rubbo, S. D., Stratford, B. C., Dixson, S. Brit. med. J. 1962, ii, 282. Davis, R. R., Noble, W. C. Lancet, 1962, ii, 1295.
skin-scales and not on textile fibres. But, although bacteria may be spread by bedding, the proportion of the total staphylococcal traffic for which they are responsible is by no means clear. HowE and MARSTON concluded that blankets and other inanimate objects do not play a major part in initiating infection in surgical patients, and WILLIAMS et al.1o observed no reduction of crossinfection after introducing regular disinfection of cotton blankets. On the other hand, ROUNTREE and BEARD3í obtained evidence that in some patients the route of infection is from bedclothes to wound; and GILLESPIE et al. 21 suggested that the disinfection of bedding con. tributed to the reduction of cross-infection which followed their combination of precautions. These discrepancies probably arise from the fact that routes of spread are many, and that the interruption of one, how. ever important, may have little observable effect. Probably, too, the speed with which blankets become recontaminated is such that they must be disinfected very frequently if much benefit is to be obtained. We badly need more investigation of this problem, and of the economics of frequently disinfecting blankets by the several methods now available.35 Without dependable statistics it is impossible to assess the size of the staphylococcal problem or to determine the value of control measures. Insufficient attention has been given to ascertainment of infections, except in the few hospitals where research on cross-infection is pursued. The detection and recording of all infections, trivial and serious, the identification of important sources of cross-infection, the correlation of clinical and laboratory findings, and the supervision of special precautions all take more time than can be spared by busy doctors and nurses. GARDNER et al.36 met these difficulties by appointing a full-time sister to work with their control-of-infection team. This approach might be considered in hospitals where staphylococci are causing serious trouble
Mineral or Matrix ? THE problem of the pathogenesis of osteoporosis continues to exercise clinicians, radiologists, pathologists, and others. First distinguished histologically from osteomalacia by POMMER in 1885,37 it was not clearly defined clinically until ALBRIGHT and his associates reported their first series of cases in 1941.38 ALBRIGHT’S concept that osteoporosis was due to diminished osteoblastic activity or to a primary disorder of the protein matrix of bone was only slowly accepted, but finally became firmly established. As usual, the heterodoxy of yesterday has become the orthodoxy of today, and now it is the challengers of this hypothesis who are regarded as the rebels. But new techniques have appeared which enable widely held views to be put to the test, and the result is controversy where ten years ago there was only dogma. 34. Rountree, P. M., Beard, M. A. J. Hyg., Camb. 1962, 60, 387. 35. The Sterilisation of Hospital Wool Blankets. International Wool Secretariat, London, 1962. A. M. 36. Gardner, N., Stamp, M., Bowgen, J. A., Moore, B. Lancet, 1962, ii, 710. 37. Pommer, G. Rachitis und Osteomalacie. Leipzig, 1885. 38. Albright, F., Smith, P. H., Richardson, A. M. J. Amer. med. Ass. 1941, 116, 2465.