Susceptibility trends in bacteraemias: analyses of 7544 patient-unique bacteraemic episodes spanning 11 years (1990–2000)

Journal of Hospital Infection (2003) 55, 196–203

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Susceptibility trends in bacteraemias: analyses of 7544 patient-unique bacteraemic episodes spanning 11 years (1990 –2000) D. Raveha, B. Rudenskyb, Y. Schlesingera, S. Benensona, A.M. Yinnona,* a

Infectious Disease Unit, Shaare Zedek Medical Center, P.O. Box 3235, Jerusalem 91031, affiliated with the Faculty of Health Sciences, Ben Gurion University of the Negev, Be’er Sheva, Israel b Clinical Microbiology Laboratory, Shaare Zedek Medical Center, P.O. Box 3235, Jerusalem 91031, affiliated with the Faculty of Health Sciences, Ben Gurion University of the Negev, Be’er Sheva, Israel Received 7 November 2002; accepted 19 June 2003

KEYWORDS Bacteraemia; Blood cultures; Antimicrobials; Antibiotics; In vitro susceptibilities

Summary The aim of the present study was to design more accurate tools for the selection of appropriate antimicrobial therapy for hospitalized patients with suspected sepsis. We created a large database comprising data on all patient-unique blood cultures obtained over an 11 year period (1 January, 1990 through 31 December, 2000). Improved statistical tools were applied to assess the trends in in vitro activity of individual antibiotic agents against various bacteria over time, and to calculate susceptibility rates of subsets of organisms. During the 11 year study period, 173 571 blood cultures were obtained, of which 17 703 (10.2%) were positive, with 7544 patient-unique blood cultures (4.3%). The mean annual number of positive, patient-unique cultures was 686 (standard deviation ¼ 79). The 10 most frequently isolated organisms were: Escherichia coli (1494), Staphylococcus aureus (1240), Klebsiella pneumoniae (779), Enterococcus spp. (631), Pseudomonas aeruginosa (488), Streptococcus pneumoniae (447), Enterobacter spp. (338), Acinetobacter spp. (298), Proteus mirabilis (260) and Candida spp. (254). No significant change was detected in the annual rates (means, standard deviations) per 1000 admissions of these organisms: the highest was E. coli (5.5, 1), the lowest was Candida (1, 0.3). Forty percent of organisms ðN ¼ 2943Þ were obtained from patients in the emergency department (ED), 23% (1744) in medical departments, 15% (1134) in paediatric units, 13% (998) on surgical wards and 9% (709) in intensive care units (ICUs). Trend statistical analysis revealed a significant decrease in susceptibility in ED Enterobacteriaceae to eight of 15 (53%) tested antimicrobials, with a mean annual decrease of 1.6% ^ 0.6%, in the ICU isolates, a significant decrease was detected in only five (33%) of the tested antimicrobials, with a mean annual decrease of 2.5% ^ 1.3%. The difference in susceptibility between ED and ICU isolates was significant for all antimicrobials ðP , 0:001Þ: A significant

*Corresponding author. Tel.: þ 972-2-6555076; fax: þ 972-26555076. E-mail address: [email protected] 0195-6701/$ - see front matter Q 2003 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/S0195-6701(03)00286-X

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decrease in the susceptibility of E coli to nine of 15 drugs (60%) was detected, ranging from 0.7% to 2.7% annually. In K. pneumoniae a significant decrease in susceptibility of K. pneumoniae was detected with only two agents. Pseudomonas spp. isolates remained highly sensitive to all traditional antipseudomonal agents, without significant decay in sensitivity rates over time. Susceptibility of S. aureus to methicillin decreased significantly for several subsets of patients ðP , 0:001Þ: Marked differences in susceptibility rates between the departments were detected. Trend statistical analyses, when appropriately applied to multi-year databases of microbial susceptibilities, may yield susceptibility tables that are significantly more accurate than traditional semi-annual or annual tables. Q 2003 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

Introduction Patients with moderate to severe infections are usually treated with antimicrobial agents before results of relevant cultures are available. Isolation of pathogens and susceptibility testing may subsequently lead to changes in antimicrobial management.1 – 3 The appropriate empiric treatment, selected when the patient is most severely ill, is of critical importance for survival and wellbeing.4 – 6 Many factors have to be considered when choosing empiric treatment: foremost are the principal pathogens causing the specific infection and their antimicrobial susceptibility patterns.1,2 These factors are very much locationspecific.7,8 It is therefore important that physicians have access to microbiological data pertaining to the patient population they serve. Computers are essential tools in the generation of these data. Most microbiology laboratories issue annual or semi-annual summary results. The overall total of evaluated organisms is usually small, often numbering several hundred at most. Therefore, organismspecific susceptibility rates are often calculated based on denominators of less than 100 isolates, which reduces their reliability as accurate predictors of antimicrobial susceptibility in the individual patient. The aim of the present study was to design more accurate tools for the selection of appropriate antimicrobial therapy for hospitalized patients with suspected sepsis. We created a large database comprising data on patient-specific blood cultures obtained over an 11 year period between 1990 – 2000. We applied well-established statistical tools, which until now have been used infrequently for this particular purpose, to assess the trends in in vitro activity of individual antibiotic agents against various bacteria over time, and to calculate susceptibility rates of subsets of blood-culture

specimens. We believe that the resulting susceptibility tables are significantly more accurate, although slightly more complicated, than traditional semi-annual or annual tables.

Methods This study was carried out in a 550-bed universityaffiliated general hospital, Jerusalem’s second largest. The hospital includes all major departments and services including three medical and two geriatric wards, haematology and oncology; paediatrics; two surgical departments specializing in vascular surgery, gynaecology and obstetrics, heart and chest surgery, urology, orthopaedics, plastic surgery, ophthalmology, otorhinolaryngology; and several intensive care units (ICUs; medical, surgical, paediatric and neonatology). Transplantations are not performed. Many patients are admitted through the Emergency Department (ED), where about 75 000 patients are seen annually. The number of admissions increased from 18 783 in 1990 to 31 823 in 2000, an increase of 69%; the number of admission days increased correspondingly from 111 949 to 161 857 (45%). These changes reflect the population growth in the Jerusalem area and the increase in the hospital’s services. The microbiology laboratory currently receives approximately 20 000 blood culture sets each year for diagnostic work-up. A set consists of an aerobic and anaerobic bottle, cultured by using the BACTEC 9240 (Becton Dickenson Diagnostic Instrument Systems, Sparks, MD, USA). Blood culture bottles are routinely incubated for up to five days unless prolonged incubation is clinically indicated. Terminal subcultures are not routinely performed unless clinically indicated. Isolates are identified using the API system (bioMe ´rieux, Marcy l’Etoile, France).

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Instrument-generated positive cultures are Gramstained or acridine-stained and plated, with subsequent sensitivity testing by the Kirby – Bauer method.9 Minimal inhibitory concentrations are not routinely performed unless clinically indicated, and are then performed with the E-test (PDM epsilometer, AB Biodisk, Solna, Sweden).10 Data from blood cultures from 1 January 1990 through 31 December 2000 were entered on-line into a commercial clinical microbiology program, based on Access (Microsoft Co). Relevant data included date of culture, the patient’s identification number, department, isolated organisms, number of a patient’s positive blood cultures with the same organism, and results of susceptibility testing for up to 18 antimicrobial agents. For analysis of antimicrobial susceptibilities an organism isolated from any patient was considered only once, even though the same organism may have grown from more than one culture set. Growth of coagulase-negative staphylococci (CNS), diphtheroids, bacilli, micrococci and alpha-haemolytic streptococci in blood cultures was considered significant only if isolated from multiple cultures or from clinically compatible event such as endocarditis. Results were analysed with statistical tools provided by the Access program and SPSS version 10.0 (statistical package for the social sciences). The chi-square test was used to analyse the association between bacterial susceptibility and time.11,12 To detect possible trends in the pattern of bacterial susceptibilities to various antimicrobials over the 11 year study period, we applied the TREND statistical tools from the PEPI epidemiological program collection.13 A typical trend analysis includes several tests; analysing these in combination can provide evidence or absence of existence of a trend. A trend was deemed not to exist (designated as NS) if the chi-square for association was not significant, or if the chi-square for association was significant but the chi-square for trend was not significant. To determine that a trend exists and is statistically valid, the P-value of the chi-square for association had to be significant (defined as P , 0:05) Second, the chi-square for trend had to be significant, regardless of whether there was a departure from a linear trend. Whenever a significant trend was detected, the P-value was provided. In addition, the regression coefficient, or slope, was calculated. This parameter indicates the change in the y-axis (percentage of susceptibility), divided by the change in the x-axis (years). A negative slope (designated as 2 ) indicates a decrease in susceptibility over time, whereas a positive slope (desig-

D. Raveh et al.

nated as þ ) attests to an increase of susceptibility over time.14

Results During the 11 year study period (1990 –2000), the number of blood drawn cultures increased from 8730 in 1990 to 18 161 cultures in 2000, making a total of 173 571 (Table I). Of these, 17 703 blood cultures (10.2%) were positive, or 7544 patientspecific cultures (4.3%), excluding obvious contaminants as defined under Methods. The 10 most frequently isolated organisms are presented in Table I. Escherichia coli was the Gram-negative bacillus most commonly isolated from communityacquired bacteraemic episodes, whereas Klebsiella pneumoniae was most commonly isolated from nosocomial bacteraemic events. The annual rate/ 1000 admissions did not change significantly throughout the study period for any of these organisms separately, or for the combined Enterobacteriaceae. The breakdown of positive cultures by departments is shown in Figure 1, with the ED being the source of most of the positive cultures (40%). Antimicrobial susceptibility rates of various subgroups of organisms are presented in Tables II – IV, and are expressed as annual means and standard deviations, alongside trend analyses for each drug. The latter included the significance of the trend, the direction of the trend and the yearly change (%). A significant decrease in susceptibility for all Enterobacteriaceae was observed with nine of 15 (60%) tested antimicrobials, with a mean annual decrease of 1.3% ^ 0.5%. A significant decrease in susceptibility was detected in ED Enterobacteriaceae to eight of 15 (53%) tested antimicrobials, with a mean annual decrease of 1.6% ^ 0.6%. In the ICUs isolates a significant decrease was detected in only five (33%; NS) of the tested antimicrobials, with a mean decrease of 2.5% ^ 1.3%. The difference in susceptibility between the ED and ICUs isolates was significant for all antimicrobials ðP , 0:001Þ; except for imipenem – cilastatin. Table III shows the changes in susceptibility for E. coli, while Table IV shows the results for K. pneumoniae. Interestingly, E. coli strains demonstrated a significant decrease in susceptibility to nine of 15 tested agents, while the K. pneumoniae strains demonstrated such a decrease to only two agents: ciprofloxacin and piperacillintazobactam. Klebsiella isolates were less susceptible than E. coli to all antimicrobials (P , 0:001 for all drugs, except imipenem–cilastatin).

Susceptibility trends in bacteraemias

Pseudomonas aeruginosa bacteraemia was detected in 488 patients during this 11 year study period, with an unchanging annual rate per 1000 patients. The organisms were susceptible to gentamicin (83%), amikacin (91%), mezlocillin (76%), piperacillin –tazobactam (95%), ceftazidime (94%), and ciprofloxacin (76%). No statistically significant changes in susceptibility to any of these drugs were observed during the study period. Pseudomonas strains were more susceptible to mezlocillin than were all subsets of Enterobacteriaceae ðP , 0:001Þ: Staphylococcus aureus was the second most frequently isolated organism. Figure 2 shows the decreasing susceptibility to methicillin of all subsets of staphylococci, including those obtained from patients admitted through the ED. In the latter group of 350 patients, methicillin susceptibility decreased from 90% in 1995 to 64% in 2000 ðP , 0:001Þ: Trend analyses revealed the decrease to be significant for total isolates (N ¼ 1237, P , 0.001), isolates obtained in the ED (N ¼ 350, P , 0.01), isolates obtained in the medical departments (N ¼ 307, P , 0.05) and paediatrics (N ¼ 65, P , 0.05). The decrease was not significant for the subset obtained in the ICUs (N ¼ 117), surgical departments (N ¼ 129), neonatology unit (N ¼ 45), paediatric dialysis unit (N ¼ 40) and geriatrics (N ¼ 110).

Discussion Recent reports from the United States have

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Figure 1 Number of positive patient-specific blood cultures: breakdown by department (N ¼ 7544) (a) Includes: ambulatory; cardiothoracic, paediatric, plastic, general and vascular surgery; urology; oto-rhinolaryngology; obsterics & gynaecology; orthopaedics. (b) Includes: neonatology, paediatric day hospital, paediatric dialysis unit, paediatric intensive care unit, department of paediatrics. (c) Intensive care unit. (d) Emergency department. (e) Includes: three internal medicine departments, acute geriatrics; haematology; haematology – oncology day hospital; adult dialysis unit.

indicated an increased proportion of hospital admissions and subsequent increase in mortality due to infectious diseases.15,16 Mortality due to bacteraemia has greatly increased, especially in the elderly, in whom this diagnosis is becoming increasingly more common.17,18 In bacteraemic patients antimicrobial therapy is usually initiated before laboratory results are received. Because it has been shown that appropriate therapy can significantly

Table I Number (%) of positive cultures/drawn cultures and rates of the most frequently isolated patient-specific organisms/1000 admissions Variable/year

Annual mean (standard deviation)

11 Year total

Drawn blood cultures ðNÞ Positive blood cultures ðNÞ Rate of positive blood cultures (%) Patient-specific positive blood cultures ðNÞ Patient-specific positive blood cultures (%) Rate/1000 admissionsa Enterobacteriaceae Escherichia coli Staphylococcus aureus Klebsiella pneumoniae Enterococcus spp. Pseudomonas aeruginosa Streptococcus pneumoniae Enterobacter spp. Acinetobacter spp. Proteus mirabilis Canadida spp.

15779 (4787) 1609 (524) 10.2 (1.5) 686 (79) 4.3 (0.6)

173571 17703 10.2 7544 4.3

12.7 (2) 5.5 (1) 4.7 (0.9) 3 (0.8) 2.3 (0.7) 1.9 (0.5) 1.7 (0.4) 1.3 (0.5) 1 (0.3) 1 (0.2) 1 (0.3)

3394 1494 1240 779 631 488 447 338 298 260 254

a

Trend statistical analysis demonstrated an absence of significant changes in annual incidence of any of these organisms during the study period.

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Table II Change in antimicrobial susceptibility (%) of subsets of Enterobacteriaceae Drug

Amp Aug Mez Tzp Imp Cef Cxm Cro Caz Cep Gen Amk Chl Sept Cip

EDa Enterobacteriaceae ðN ¼ 1277Þ

All Enterobacteriaceae ðN ¼ 3394Þ

ICUa Enterobacteriaceae ðN ¼ 313Þ

Mean (SD)b

Mean (SD)b

Mean (SD)b

Trend analysisc

36 (11) 56 (3) 52 (9) 91 (2) 100 56 (11) 81 (7) 91 (6) 91 (13) 87 (1) 87 (7) 98 (2) 72 (6) 64 (8) 83 (8)

P

%

0.001 NS 0.001 NS NS 0.001 0.001 0.001 0.001 NS 0.001 0.001 NS NS 0.001

22.5

Trend analysisc

27 (7) 46 (6) 51 (8) 85 (2) 100 43 (5) 67 (4) 80 (6) 72 (17) 77 (13) 78 (7) 93 (3) 65 (4) 61 (7) 77 (9)

21.8

21.6 21.4 21.7 þ 1.3 21.3 20.4

21.9

P

%

0.001 NS 0.001 NS NS 0.01 0.05 0.001 0.001 NS 0.001 NS 0.05 0.01 0.001

21.8

Trend analysisc P

21.9

20.9 20.7 21.4 þ 3.1 21.5 21 20.8 22.1

11 (11) 32 35 (20) 68 (15) 100 (1) 20 (10) 32 (15) 50 (16) 49 (24) 68 (9) 53 (21) 78 (15) 37 (14) 44 (19) 51 (18)

%

NS NS NS NS 0.05 NS NS 0.05 NS NS NS NS 0.05 0.01 0.01

20.3

22.2

23.8 22.7 23.3

Amp, ampicillin; Aug, amoxicillin–clavulanate; Mez, mezlocillin; Tzp, piperacillin–tazobactam; Imp, imipenem; Cef, cefazolin; Cxm, cefuroxime; Cro, ceftriaxone; Caz, ceftazidime; Cep, cefepime; Gen, gentamicin; Amk, amikacin; Chl, chloramphenicol; Sept, trimethoprim –sulfamethoxazole; Cip, ciprofloxacin. a ED, strains isolated from Emergency Department patients; ICU, intensive care unit. b Mean annual number of isolates; SD ¼ standard deviation. The difference in susceptibility rates between ED isolates and ICU isolates was highly significant ðP , 0:001Þ for all antimicrobials, except for imipenem–cilastatin/meropenem. c Trend analysis: P indicates significance of trend; þ or 2 indicates direction of trend, i.e., positive or negative; % indicates yearly increase or decrease in susceptibility of particular drug (%).

increase survival,4 – 6 physicians usually initiate empiric therapy based upon antimicrobial susceptibility data published in the literature,7,19 or based upon local laboratory data. Published data may not

reflect the susceptibility patterns of the individual patient’s hospital, and locally generated reports usually present either relatively small numbers of isolates or cumulative summaries, which do not

Table III Change in antimicrobial susceptibility (%) of all isolated strains of Escherichia coli ðN ¼ 1494Þ Year N

Ratea Amp Aug Mez Tzp Imp Cef Cxm Cro Caz Cep Gen Amk Chl Sept Cip

90

91

92

93

94

95

96

97

98

99

00

Mean (SD)

Trend analysis

64

85

100

100

131

144

152

188

183

190

157

130 ^ 56

P

%

6.6 32 41 38 89 100 38 74 83

4.9 26 59 35 95 100 46 75 83 93 92 74 92 76 54 70

5.5 (1) 40 (9) 50 (13) 44 (8) 93 (13) 100 58 (12) 85 (7) 91 (5) 89 (10) 84 (11) 89 (8) 96 (3) 78 (6) 63 (6) 85 (9)

NS 0.001 NS 0.001 NS NS 0.01 0.001 0.001 0.001 NS 0.001 0.001 NS 0.001 0.001

NS 22.7

3.8 50

4.7 52

5.3 49

4.6 46

5.5 52

5.8 39

53

48

50

51

54

4

55 95 98

58 93 97

100 66 88 93 100

69 93 96 83

100 64 87 92 69

100 97 79 69 98

96 99 74 65 96

98 99 80 69 96

97 97 91 74 91

91 99 76 63 80

5.9 33

7 31

6.6 36

100 55 87 94 90

36 92 100 50 78 89 89

32 96 100 59 84 93 98

39 93 100 84 83 87 94

90 94 75 57 84

85 98 73 63 77

91 99 NA 59 83

84 97 NA 61 82

76 79 89 NA 59 74

22.1

21.2 22 21.5 þ 1.5 22.4 20.7 21.4 22.5

Amp, ampicillin; Aug, amoxicillin–clavulanate; Mez, mezlocillin; Tzp, piperacillin–tazobactam; Imp, imipenem; Cef, cefazolin; Cxm, cefuroxime; Cro, ceftriaxone; Caz, ceftazidime; Cep, cefepime; Gen, gentamicin; Amk, amikacin; Chl, chloramphenicol; Sept, trimethoprim –sulfamethoxazole; Cip, ciprofloxacin; NA, not available; SD, standard deviation. a Number of annual bacteraemias per 1000 admissions.

Susceptibility trends in bacteraemias

201

Table IV Change in antimicrobial susceptibility (%) of all isolated strains of Klebsiella pneumoniae (N ¼ 779) Year N

Ratea Amp Aug Mez Tzp Imp Cef Cxm Cro Caz Cep Gen Amk Chl Sept Cip

90

91

92

93

94

95

96

97

98

99

00

Mean (SD)

Trend analysis

28

31

67

84

56

88

99

85

86

78

77

71 ^ 23

P

%

3.4 0 47 37 52 99 39 43 50 60 69 43 89 36 44 47

3 0 48 37 62 100 38 44 54 51 57 52 81 42 46 62

NS NS NS NS 0.01 NS NS NS NS 0.01 NS NS NS NS NS .01

NS

1.7 0

1.7 0

3.5 0

3.9 0

2.3 0

3.5 0

100 38 45 53 52

36 67 100 37 40 49 50

38 69 99 40 46 51 52

43 67 100 45 52 48 55

55 79 50 44 53

44 71 31 44 61

59 77

56 74

2.7 0 50 43 54 100 43 47 49 64 45 56 83

43 63

47 53

58 63

46

20

35

34

42

36

46 48 63

100 17 27 30 33b

100 36 41 55

100 38 39 63

100 43 59 79 46

29 83 30 26 50

52 83 32 54 55

64 98 46 55 78

68 79 64 46 93

43 80 44 42 64

3.8 0

3.2 0

3.1 0

(0.8) (2) (7) (8) (8) (8) (12) (9) (17) (11) (7) (12) (8) (13)

24.3

þ3

21.6

NS, non-significant. Drug definition are as per Table III; SD, standard deviation. a Rate: number of annual bacteremias per 1000 admissions. b The low susceptibility rate of ceftazidime in 1993 accentuates the fact that this drug was tested only for selected organisms up to and including 1994. From 1995 all isolates were tested; therefore, the apparent increase in susceptibility rate to ceftazidime between 1991 and 2000 is an artificial one.

reflect changes in susceptibility trends. The method employed in our study allowed for analysis of a large number of isolates and provided information as to trend of increased or decreased susceptibility. We have been able to provide a single table for clinicians with susceptibility rates of Enterobacteriaceae to 15 commonly used antimicrobials (Table II). This table includes data of all 3394 patient-unique isolates spanning 11 years, with sub-analysis of 1277 cultures obtained in the ED and 313 cultures acquired in the ICUs. A spectrum of resistance is clearly apparent, with ED isolates demonstrating significantly higher susceptible rates to all antibiotics, except imipenem – cilastatin, than ICU isolates. The ED isolates also demonstrate relatively high rates of resistance, with significant decay in efficacy of eight of 15 drugs over the study period, probably reflecting the fact that many of the patients admitted through the ED are nursing home patients, or persons re-admitted after recent discharge from hospital, in addition to community-based individuals. This table is only slightly more complicated than the standard annual or semi-annual tables issued by most clinical microbiology laboratories, but more reliable on account of its much larger data base. Our study showed K. pneumoniae to be the single most important Gram-negative organism causing nosocomial infections in our hospital, as found by others, with an associated mortality

of 40 – 50%.20 – 22 This organism is a frequent producer of extended-spectrum b-lactamases (ESBL) and has shown progressively decreasing susceptibility to fluoroquinolones.22 – 25 The decreasing efficacy of piperacillin – tazobactam that we have

Figure 2 Methicillin sensitivity (%) of Staphylococcus aureus bacteraemia. ( ) ED, N ¼ 350; ( ) All, N ¼ 1237; ( ) Medicine, N ¼ 307; ( ) ICU, N ¼ 117.

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observed in our hospital has led to our decision to remove ceftazidime from our drug formulary, in the hope that the susceptibility rate to piperacillin – tazobactam might increase.26 Currently, amikacin and meropenem are the only agents we are able to use for empiric treatment of serious infections, which might be caused by K. pneumoniae. Interestingly, we have not encountered significant development of resistance in strains of P. aeruginosa to any anti-pseudomonal drugs. Another important finding is the rapidly decreasing methicillin susceptibility of S. aureus strains, including those obtained from patients admitted through the ED. Of 350 ED patients, the susceptibility rate decreased from 90% in 1995 to 64% in 2000. These alarming figures could, be explained in part, by the fact that a substantial percentage of patients admitted through the ED actually come from nursing homes or have recently been discharged from hospital. Nonetheless, we are increasingly encountering true communityacquired infections due to methicillin-resistant S. aureus (MRSA), in patients without obvious risk factors. This observation has also been reported by others.27 – 29 Our study may have several limitations. First the observed changes in susceptibility rates could result from a change in patient population over the last decade. There is indeed much evidence to this effect; as elsewhere, we observe an increase in mean age of patients admitted, an increase in number of co-existing diseases, and a growing proportion of admissions from nursing homes. However, the data presented in this study rather reflect these changes, as they should, in order to provide the clinician with accurate and timely tools to select appropriate antimicrobial therapy for the patients currently being admitted. Second, statistical methods, although highly useful, have limitations. For example, we set the significance level at 5%, which means that a result found to be significant could be observed by chance on average for five out of 100 tests performed. However, this level is the one usually employed; moreover, in our study most significant results reached levels of 1% ðP , 0:01Þ or 0.1% ðP , 0:001Þ; minimizing the risk of chance occurrences. In conclusion, we have demonstrated that individual hospitals can produce antimicrobial susceptibility tables that are based on multiple year, patient-unique isolates, analysed with trend statistical methods, and stratified according to source of patients. We believe these tables are both useful and more accurate than traditional methods (such as national or international susceptibility data or annual tables produced by the local

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laboratory) for clinicians selecting empirical treatment for individual patients, as well as for the design of locale-unique protocols for antimicrobial therapy for specific infections.

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