The impact of methicillin- and aminoglycoside-resistant Staphylococcus aureus on the pattern of hospital-acquired infection in an acute hospital

Journal

of Hospital

Infection

(1990) 16, 231-239

The impact of methicillinand aminoglycoside-resistant Staphylococcus aureus on the pattern of hospital-acquired infection in an acute hospital P. D. Meers Microbiology

and K. Y. Leong*

Department, National *National University

Univkrsity of Singapore Hospital, Singapore

Accepted for publication

31 May

and the

1990

Summary: Infections due to methicillinStaphylococcus aureus (MARSA) appeared

and aminoglycoside-resistant in a new teaching hospital shortly after it opened. The effect this had on the pattern of hospital-acquired infections in the four years that followed is described. No control measures were applied and MARSA became endemic. New infections appeared at a rate of about four for each 1000 patients discharged. It established itself at different levels of incidence in various specialist units, patients under intensive care being most severely affected. MARSA was implicated in half of all hospital-acquired infections due to S. aureus but it was not more pathogenic than its more sensitive counterpart. It had little impact on the life of the hospital.

Keywords:

MARSA;

hospital-acquired

infections;

risk

factors;

control.

Introduction

Although strains of Staphylococcus aweus resistant to methicillin (MRSA) were reported shortly after the drug was introduced (Jevons, 1961), when strains simultaneously resistant to methicillin and an aminoglycoside (MARSA) emerged (Perceval, McLean & Wellington, 1976; Shanson, Kensit & Duke, 1976) they were thought to pose a special problem. Many publications have recorded outbreaks of infection due to the strain and most describe more or less vigorous counter-measures (Haley et al., 1982; Casewell, 1986; Brumfitt & Hamilton-Miller, 1989). The need for radical action to control MARSA has been contested (Lacey, 1987). It seemed useful to record events following the introduction of MARSA into a hospital where control measures (Working Party, 1986) were not applied. MARSA first emerged as an important pathogen in hospitals in Correspondence to: Dr Singapore 05 11. 019556701/90/070231+09

P. D. Meers,

SO3.00/0

Microbiology

Department,

National

University

0 1990 The Hospital

231

of Singapore,

Infection

Society

232

P. D. Meers

and K. Y. Leong

Singapore in 1985, though occasional strains had been detected in earlier years (Yeo, personal communication). Methods The National University Hospital (NUH) is a teaching hospital admitting patients to the usual range of acute specialities, though it has no burns unit. It opened in mid-1985, and grew slowly to reach peak utilization of its 700 beds by the beginning of 1989. A system for the collection of data on the incidence of hospital-acquired infection (HAI) operated from the outset. This was a function of the Infection Control Team (ICT) made up of the Control of Infection Officer (the hospital’s medical microbiologist) and an Infection Control Nurse (ICN), who was originally employed on a part-time basis, but was employed full-time as the hospital expanded. The ICT reported to a Control of Infection Committee. The surveillance system was partial, as it derived about 95% of its data from specimens examined in the microbiology laboratory. When the result of a culture indicated the possibility of an infection the ICN visited the ward concerned. If an infection was present it was recorded as hospital- or community-acquired, and categorized by site, speciality and causative microbe. The definitions and criteria applied were from Meers et al. (1981). Specimens from patients were collected for clinical indications, as determined by the attending physician or surgeon. Other than in the limited way indicated below neither patients nor staff were screened for MARSA. Clinical specimens were examined conventionally on the usual range of media, including 5% horse blood agar. Staphylococci were subjected to a tube coagulase test, using human plasma. Staphylococcus aweus was tested for methicillin resistance using a 5 ug disc on Mueller-Hinton agar with 5 % NaCl, incubated at 35°C or 37°C. The methods were controlled by internal and external quality assessment. A few pilot experiments were performed in which hand-rinsings collected from members of staff were examined for the presence of MARSA. Each hand was clenched and un-clenched repeatedly inside a plastic bag containing 50 ml of quarter-strength Ringer’s solution. The solution was then filtered through a 47 mm, 0.45 urn pore-size membrane. The filter was placed on the surface of 10% NaCl agar, which was incubated at 37” for 48 h. Colonies that developed were subcultured onto blood agar for further study. Small lesions on the hands of staff were sampled with a swab and examined in the same way as other clinical specimens. If MARSA was identified, further tests were done using the hand-rinsing technique usually at weekly intervals until it disappeared. A proposal to extend the pilot study was not accepted. Representative MARSA strains were collected and stored. These are being subjected to more detailed study, to be reported in due course.

MARSA

and hospital

infection

233

Results

In the four years from 1 January 1986, 113 331 in-patients passed through NUH. Of these 3275 were recorded as suffering 3888 episodes of HAI, with 4147 imputed pathogens. The annual rates of HA1 detected were 28, 27, 37 and 24 patients with one or more infections for each 1000 discharges and deaths. The types of infection and their distribution by speciality are shown in Table I, and their microbial causes are classified by the site of infection in Table II and by speciality in Table III. Strains of MARSA found in NUH were consistently resistant to methicillin, gentamicin, erythromycin and tetracycline, usually sensitive to chloramphenicol and cotrimoxazole, nearly always sensitive to fusidic acid and always sensitive to rifampicin and vancomycin. A single infection with MARSA was detected in December 1985. After a lull of two months MARSA reappeared in March 1986, when the monthly total of patient discharges and deaths had reached 1329, 473 beds were in use and three intensive care units had opened. New cases (2-21) then appeared every month. In the four years under review a total of 461 patients suffered 522 MARSA infections at annual rates of 41, 36, 41 and 43 new cases detected for every 10 000 patients. The distribution by speciality of patients who had MARSA infections is compared with the distribution of all patients with HA1 in Table I. Cultures of hand-rinsings of nurses led to the observation that minor paronychias or other trivial lesions on the hands sometimes allowed MARSA to become part of individuals’ resident flora. Carriage continued until the lesions healed, usually within 14-21 days. Another test was made on a group of nurses employed in a ward where there were patients infected with MARSA. Hand-rinsings collected without prior notice at the end of a shift contained MARSA in 2/12 day nurses and S/6 night nurses (P= 0.01, Fisher’s exact test, one-tailed). The ratio of microbiology specimens examined to patients discharged for each of the four years studied was 2.2, 2.3, 2.2 and 1.8.

Discussion

At the beginning of 1988 scrutiny of laboratory reports for evidence of HA1 was intensified. This increased the rate of detection by one-third. In 1989 the average number of specimens examined for each patient fell. This was also certainly the result of an official campaign designed to reduce hospital costs. Diagnostic laboratory tests were a particular target. Although these factors affected the quantity of HA1 detected by our laboratory-based system, the distribution of infections by anatomical site, by location in the hospital and, with one exception, by microbial cause, remained constant from year to year. The single exception was MARSA. The number of

* Ophthalmology, tract infection;

Totals:

(41)

113 331

throat & Oral OTH, other

1603

13 (45) 43 (28)

8 (6)

2 (6)

(0)

406 (53)

0

26 (15) 14(13) 11 (6) 28 (23) 289 (33) 171(43) 592 (66)

UT1

26 292 4 953 1440 12 993 4 256

676

860 785 1602 1437 19 135 10 809 28 093

Ear, nose and SEP, septicaemia;

Surgical intensive care Cardio-thoracic unit Special care baby unit Medical intensive care General Surgery Orthopaedics Obstetrics & gynaecology Paediatric intensive care General medicine Neonatal unit Coronary care Paediatrics Others*

Patients

surgery. infections;

992 (26) UTI,

(20)

77 (10) 9 (7) 0 (0) 27 (18) 18 (56)

5

43 (25) 37 (35) 9 (5) 6 (5) 372 (42) 171 (43) 218 (24)

SW1

urinary MARSA,

517(13)

2 (6)

102 (13) 13 (10) 13 (45) 21(14)

11 (44)

66 (38) 39 (37) 62 (35) 53 (43) lOl(l1) 1.5 (4) 19 (2)

RTI

Hospital-acquired

(4)

(7) (3) (3) (6) (0)

612 (16)

129 (17) 91(73) 2 (7) 51 (34) 10 (31)

6 (24)

(15) (11) (40) (25) (10) (9) (7)

OTH 26 12 70 30 86 36 63

(%)

3888

1:; 32

767 125

25

172 106 175 122 887 397 900

ALL

tract infection; SWI, surgical wound methicillinand aminoglycoside-resistant

164

53 4 1 9 0

3 (12)

8 (1)

4 (4) 23 (13) 5 (4) 39 (4) 4 (1)

11 (6)

SEP

infections

with

infection; RTI, S. aureus.

29

25 24 17 10 5

28

4;

109 107 89 69 38

Patients with HA1 /lOOO

respiratory

41

2 14 17 5

89

233 217 306 167 62 72 1

Patients MARSA /10000

Table I. The distribution of hospital-acquired infections (HAI; one or more in each patient), of patients with HAI and of patients with infections due to methicillin- and aminoglycoside-resistant Staphylococcus aureus in the National University Hospital, Singapore, from January 198iGDecember 1989

cd

MARSA

and hospital

infection

235

Table II. The distribution of bacterial pathogens causing hospital-acquired infections (HAI) in the National University Hospital, Singapore, from January 1986 to December 1989, according to the type of infection Hospital-acquired

infection

HA1

-Causative

organisms

MSSA

MARSA

GNR

28 (2)

Urinary tract infection Surgical wound infection Respiratory tract infection Septicaemia Surface infection Other infections

1092 430 236 79 68 69

(64) (36) (44) (46) (2.5) (25)

258 40 18 68 79

Totals

1974

(48)

491 (12)

GNR, Gram-negative and aminoglycoside-resistant

Table

III.

the National

rod;

(22) (7) (11) (25) (28)

(W)

MARSA Others

% SAA

46 (3) 217 (18) 134 (25) 18(11) 7.5 (27) 32(11)

539 (32) 277 (23) 125 (23) 56 (33) 64(23) 99 (35)

62 46 77 50 52 29

522 (13)

1160

52

MSSA, methicillin-sensitive S. S. aureus; SAA, all S. aureus.

(28)

awe-us; MARSA,

methicillin-

The distribution of bacterial pathogens causing hospital-acquired infections (HAI) in University Hospital, Singapore, from January 1986 to December 1989, according to speciality HAI-Causative GNR

Surgical Intensive Care Cardio-thoracic Special care baby unit Medical Intensive Care General surgery Orthopaedics Obstetrics & gynaecology Paediatric intensive care General medicine Neonatal unit Coronary care Paediatrics Others* Totals: * Ophthalmology, methicillin-sensitive

Ear,

99 46 39 67 503 236 391

(52) (48) (20) (42) (51) (52) (46)

8 (28) 463 (57) 31 (21) 17 (53) 63 (40) 11(35) 1974 (48)

(%)

MSSA

MARSA

Others

8 (4) 9 (9) 29 (15)

30 (16) 18 (19) 66 (33) 26 (16) 130 (13) 90 (20) 7 (1) 9 (31) 102 (12) 16(11) 3 (9) 22 (14) 3 (10) 522 (13)

53 (28)

12 03) 97 (10) 39 (9) 122 (14) 4 (14)

62 (8) 66 (45) 3 (9) 32 (20)

8 (26) 491(12)

nose and throat & Oral S. aureus; MARSA,

organisms

surgery, methicillin-

GNR,

22 65 54 267 85 323

(23) (33) (34) (27) (19) (38)

Totals 190 1:; 159 997 450 843

8 (28) 192 33 9 40 9 1160

(23) (23) (28) (25) (29) (28)

8:; 146 32 157 31 4147

Gram-negative rod; MSSA, and aminoglycoside-resistant

S. aureus.

strains of this organism isolated did not change to reflect movements in the proportion of HA1 that was detected. One reason for this was that laboratory staff more readily drew attention to MARSA as a probable cause of HA1 than was the case with other bacteria. It may also be that MARSA infections were found in sites or in types of patient more likely to be examined bacteriologically, even when testing was discouraged. This evidence, together with the fact that clinical surveillance was carried

236

P. D. Meers

and K. Y. Leong

out throughout by the same ICN (KYL), leads us to believe that although the proportion of the total of HA1 detected varied over the period studied, the distribution of its components relative to each other did not. We have not been able to measure the proportion of total HA1 detected by our system, but think that overall it has been between 25 and 50%. A partial laboratory-based system of surveillance suffers from the confounding effect of variations in sampling between clinical areas. It is probable that infections in intensive care units were more completely represented in our data than those from other parts of the hospital, and that the record of hospital-acquired septicaemias was nearly complete. Laboratory-based surveillance can attain a sensitivity approaching 100% (Hambraeus & Malmborg, 1977) but this is not true when patients are billed by item of service; accounts are updated before specimens reach the laboratory bench and staff are inculcated with an awareness of costs. Despite this, the distribution of HA1 recorded in NUH is similar to that seen in much of Europe and N. America (compare Tables I and II with the findings of Haley et al., 1985). Although the total incidence of HA1 is not known, compared with experience elsewhere, it seemed much the same as in other developed countries. Staphylococcus aureus was the infecting organism in 24% of cases of HA1 in NUH, divided almost equally between methicillin-sensitive (MSSA) strains on one hand, and MARSA on the other. We cannot establish what the rate of MSSA infections would have been in the absence of MARSA. In a prevalence study in the UK when MARSA was not widespread, S. uureus accounted for 18% of the infections recorded (Meers et al., 1981). A similar study in Sweden produced a rate of 12% (Bernander et al., 1978). Incidence rates of S. aureus infections of about 10% were regularly reported in the National Nosocomial Infections Study in the USA (Center for Disease Control, 1978, 1981, and Haley, 1986), though Eickhoff et al. (1969) found it to be 23% in six US hospitals and McGowan & Finland (1974) recorded a figure of 22% in Boston. For NUH we cannot say if the emergence of MARSA has increased the size of the pool of pathology due to S. aureus. No inference can be made from these data about the comparative pathogenicity of MSSA and MARSA. Another approach is to examine the results of blood cultures. The 171 bacterial pathogens isolated from cases of hospital-acquired septicaemia included exactly equal numbers of MSSA and MARSA (Table II). As this tallies with their overall distribution, it seems that they do not differ in pathogenicity. This agrees with our clinical impression and with the findings of Thompson, Cabezudo & Wenzel (1982). The rate of appearance of new MARSA infections varied from month to month, but taken over longer periods it very quickly stabilized at about four for each 1000 discharges. This is a little lower than the rate current during most of the outbreak described by Linnemann et al. (1982). The hospital concerned contained a burns unit and control measures were applied. These

MARSA

and hospital

infection

237

factors ought to operate in opposite directions, and if allowance is made for the NUH shortfall in sensitivity, the incidences in the two hospitals appear similar. It is noteworthy that despite vigorous attempts at control, Linnemann et al. had no success until the burns patients were moved into a new self-contained unit. The distribution of MARSA within NUH differed in certain respects from the general distribution of HA1 (Table I). It also varied in total and as a proportion of S. aureus causing infections (Tables II, III). These results once more document the importance of intensive care units in the epidemiology of MARSA as well as of HA1 in general (Thompson et al., 1982). There are interesting differences in the rank orders of the incidences of HA1 as a whole and of MARSA infections (Table I). These underline the particular susceptibility of infants to staphylococci (Allen, 1986). The differences were consistent from year to year, so were almost certainly inherent. They probably depended primarily on the nature of the procedures performed in each unit, and secondarily on multiple transmission between colonized or infected patients and staff (Haley et al., 1982). As we could not screen the staff we cannot say if long-term carriage played a part though staff changes over four years make it less likely. The ratios of infections due to MSSA to those caused by MARSA vary with their site (Table II). The differences are consistent with the view that cross-infection is more usually the cause of hospital-acquired urinary and respiratory infections, while self-infection is more common at other sites. We have recorded our experience in a hospital where MARSA became endemic, with a rate of acquisition and distribution by speciality that rapidly stabilized and then remained constant for four years. It is likely that hospitals require a certain ‘critical mass’ of patients to sustain MARSA infections in endemic form. This mass will vary according to the numbers of patients with different levels of susceptibility to infection: those in intensive care or a burns unit, for instance, will contribute more to the total. In NUH the critical level was reached when the number of beds occupied approached 500 and three of a final total of six intensive care units were in operation. The observation concerning size accords with the experience of Haley et al. (1982) in the USA. When judging the validity of a claim that control measures have eliminated or excluded MARSA from a hospital, it may be necessary to take into account its size, and the number of specially susceptible patients it contains. In NUH the most noticeable effect of the presence of MARSA was to increase the use of vancomycin. Although minor concern was generated there were no ward closures, no disruption of clinical services, and virtually no expenditure on specific control measures other than antimicrobials. In the absence of MARSA, patients who were infected with it would almost certainly have been infected with another, though therapeutically less costly, pathogen. Numerous cases of HA1 caused by multi-resistant Gram-negative bacilli as well as by MSSA point to the availability of

238

P. D. Meers

and K. Y. Leong

alternatives (Tables II, I II). We did not find any evidence of an increase in morbidity or mortality due to MARSA as compared with any other pathogen. Although patients had to pay more when they acquired an infection with MARSA, from administrative and commercial points of view the hospital carried on as if the infection did not exist. On this basis, inactivity (Lacey, 1987) was justified. Attempts to control MARSA are expensive and disruptive (Linnemann et al., 1982; Lacey, 1987; Mehtar, Drabu & Mayet, 1989). It may be argued that it is necessary to keep the numbers of MARSA as small as possible to reduce the chances of a mutation to vancomycin resistance or an increase in virulence to match that attributed to the ‘80/81’ strain in the 1950s. The more patients colonized or infected with MARSA, the greater the risk that these ‘ultimate’ staphylococcal pathogens will emerge. One justification for attempting to control MARSA would be to show that the methods used significantly restricted the population of it. This is unlikely for two reasons. First (and most significantly) on a global scale hospitals where control is attempted are greatly outnumbered by those where MARSA is uncontrolled or even undetected. Second (and more arguably) the measures used to control MARSA have not been applied in a controlled fashion, so no estimate can be made of their effectiveness, much less their cost-effectiveness. Because of the necessary delay in the microbiological identification of persons infected or colonized by specific microbes, the two principal measures employed (isolation and screening) are flawed. For the time being any differences of opinion about what could or should be done to control MARSA cannot be resolved. Because the emergence of an ‘ultimate’ staphylococcus would settle it most conclusively, we hope the debate continues, though it is unlikely to alter the eventual outcome. What is or is not done internationally about HA1 or MARSA depends on politics and economics and the workings of individual health-care systems, modified by the readiness of patients to sue for iatrogenic injury. Ideas and practice concerning these determinants are changing rapidly, not always for the better. Many people helped to collect due to Drs Mavis Yeo, Julia provided helpful criticism.

the data used in compiling Heptonstall and Gamini

this report. Kumarasinghe.

Particular thanks are Dr David Bassett

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and hospital

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