7
ORIGINAL INVESTIGATION Age- and Sex-Associated Trends in Bloodstream Infection  A Population-Based Study in Olmsted County, Minnesota Daniel Z. Uslan, MD; Sarah J. Crane, MD; James M. Steckelberg, MD; Franklin R. Cockerill III, MD;  Jennifer L. St. Sauver, PhD; Walter R . Wilson, MD; Larry M. Baddour, MD Background: Despite increasing concerns about anti- mic rob ial resi sta nce and eme rgi ng path oge ns amo ng blo od cult ure iso late s, con temp orar y pop ulat ion- bas ed data on the age- and sex-specific incidence of bloodstream in- fections (BSIs) are limited. Methods: Retro spec tive, popu latio n-ba sed, cohort study of al l res idents of Ol ms ted County, Mi nnes ot a, wi th a BS I between January 1, 2003, and December 31, 2005. The medical record linkage system of the Rochester Epide- miology Project and microbiology records were used to identify incident cases. Results: A total of 1051 unique patients with positive blood culture results were identified; 401 (38.2%) were classified as contaminated. Of 650 patients with cul- tures deemed clinically relevant, the mean±SD age was 63.1±23.1 years, and 52.5% were male. The most com- mon organisms identified were Escherichia coli  (in 163 pat ien ts wit h BSIs [25.1%]) and Staph yloco ccus aureus (in 108 patients with BSIs [16.6%]). Nosocomial BSIs were more common in males than females (23.8% vs 13.9%; P =.002 ). The age -ad jus ted inc ide nce rate of BSI wa s 156 per 100000 person -ye ars for female s and 23 7 per 10 0 000 person-years for males (P.001), with an age- and sex- adjusted rate of 189 per 100 000 person-yea rs. Rates of BSI due to gram-positive cocci were 64 per 100 000 per- son-years for females and 133 per 100 000 person-years fo r ma le s (P.00 1); gram -neg ative bac ill us BSI rate s (85 / 100000 pers on- yea rs forfemales and 79/ 100000 per son - years for males) were not significantly different be- twee n sexe s (P =.79). The rate of  S aur eus BS I wa s 23per 100 00 0 pe rso n- ye ar s fo r fe ma le s and 46 pe r 100 00 0 pe r- son-years for males (P =.005). Conclusions: The re are sig nif icant dif fere nces in the age and sex distribution of organisms among patients with BSI s. The inc ide nce of BSI increasesshar ply wit h incr eas - ing age and is significantly higher in males, mainly be- cause of nosocomial organisms, including S aureus.  Arch Inter n Med. 2007;16 7:834-8 39 M ORTA LITY FROM BLOOD- stream infections (BSIs ) remains high, wit h a case -fat alit y rate ashig h as 20% to30%, despite significant advances in antimicro- bial therapy and automated blood culture techniques. 1-3 Con cern s about increas ing an- timicr obial resistance among blood iso- lat es hav e bee n not ed, esp eci all y due to or- ganisms with limited availa ble treatmen t options, such as extended-spectrum -lactamase– producing gram-negative ba- cill i or methicil lin- resis tant Staphylococcus aureus. 4 Rec ent dat a sug ges t tha t rat es of BSI du e to S aur eus have been incre asing , 5,6 with the rate of nos oco mia l prim ary S aureus BSI more than doubling. 7 Previous European observations of BSIs from the 1980s and 1990s hav e esti mat ed inc ide nce rates of BSI to be be twee n 76.5and 15 3 pe r 100 00 0. 8,9 Ther e has been sp ec ul atio n that as ra tes of BS I inc rea se, com pli cat io ns of BS I, suc h as infective endocarditis (IE) 10 and vertebral osteomyelitis, 11 also will increase. 12 How- eve r, ther e hav e bee n min ima l rece nt pop u- lation-based data evaluating trends in BSI, and it is unclear which populations are at highest risk for BSI due to different organ- isms. Such data are necessary for targeting treat ment and prev entio n effo rts. We, there- fore, cond ucted a retrospective, popu latio n- ba sed , cohortstudyto eva lua te age-andsex- ass ociate d tre nds in the inc id enc e of BS I in a geographically defined population. METHODS STUDY SETTING Olms ted Count y is locate d in south easte rn Min- neso ta and has pop ulat ion characteristics simi- lar to those of US non-Hispanic whites. 13 The population according to the 2000 census was 124 277. There is a low prevalence of intrave - nous drug abuse. 14 The Rochester Epidemiol- ogy Project is a medi calrecor d lin kage sy stem thatindexes medical recor ds from all indi vidu - Author Affiliations: Divisions of Infectious Diseases (Drs Uslan, Steckelberg,  Wilson, and Baddour) and Primary Care Internal Medicine (Dr Crane), Department of Medicine, Division of Microbiology, Department of Pathology (Dr Cockerill), and Department of Health Sciences Research (Dr St. Sauver), Mayo Clinic College of Medicine, Rochester, Minn. Dr Uslan is now with the Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, Calif. (REPR INTED) AR CH INTER N MED/VOL 167, APR 23, 2007 WWW.ARCHINTER NMED.COM 834 ©2007 American Medical Association. All rights reserved. Downloaded From: http://archinte.jamanetwork.com/ on 01/30/2015

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ORIGINAL INVESTIGATION

Age- and Sex-Associated Trendsin Bloodstream Infection

 A Population-Based Study in Olmsted County, Minnesota

Daniel Z. Uslan, MD; Sarah J. Crane, MD; James M. Steckelberg, MD; Franklin R. Cockerill III, MD; Jennifer L. St. Sauver, PhD; Walter R. Wilson, MD; Larry M. Baddour, MD

Background: Despite increasing concerns about anti-microbialresistanceandemerging pathogens among bloodculture isolates, contemporary population-based data onthe age- and sex-specific incidence of bloodstream in-fections (BSIs) are limited.

Methods: Retrospective,population-based, cohort studyof all residents of Olmsted County, Minnesota, with a BSIbetween January 1, 2003, and December 31, 2005. Themedical record linkage system of the Rochester Epide-miology Project and microbiology records were used toidentify incident cases.

Results: A total of 1051 unique patients with positiveblood culture results were identified; 401 (38.2%) wereclassified as contaminated. Of 650 patients with cul-tures deemed clinically relevant, the mean±SD age was63.1±23.1 years, and 52.5% were male. The most com-mon organisms identified were Escherichia coli (in 163patients with BSIs [25.1%]) and Staphylococcus aureus(in108 patients with BSIs [16.6%]). Nosocomial BSIs were

more common in males than females (23.8% vs 13.9%;P =.002). The age-adjusted incidence rate of BSI was 156per 100000 person-years for females and 237 per 100 000person-years for males (P.001), with an age- and sex-adjusted rate of 189 per 100 000 person-years. Rates of BSI due to gram-positive cocci were 64 per 100 000 per-son-years for females and 133 per 100 000 person-yearsfor males (P.001); gram-negative bacillus BSI rates (85/ 100000 person-years for females and 79/100000 person-years for males) were not significantly different be-tween sexes (P =.79). The rate of S aureus BSI was 23per100 000 person-years for females and 46 per 100 000 per-son-years for males (P =.005).

Conclusions: There are significant differences in the ageand sex distribution of organisms among patients withBSIs. The incidence of BSI increases sharply with increas-ing age and is significantly higher in males, mainly be-cause of nosocomial organisms, including S aureus.

 Arch Intern Med. 2007;167:834-839

MORTALITY FROM BLOOD-s t r e a m i n f e c t i o n s(BSIs) remains high,with a case-fatality rateashigh as 20% to30%,

despite significant advances in antimicro-bial therapy and automated blood culturetechniques.1-3 Concerns about increasingan-timicrobial resistance among blood iso-lates have been noted, especially dueto or-ganisms with limited available treatmentoptions, such as extended-spectrum-lactamase–producing gram-negative ba-

cilli or methicillin-resistant Staphylococcusaureus.4 Recentdata suggest that rates ofBSIdue to S aureushavebeenincreasing,5,6 withthe rateof nosocomial primaryS aureus BSImore than doubling.7 Previous Europeanobservations of BSIs from the 1980s and1990s have estimated incidence rates of BSIto be between 76.5 and 153 per 100 000.8,9

There has been speculation that as rates of BSI increase, complications of BSI, such asinfective endocarditis (IE)10 and vertebral

osteomyelitis,11 also will increase.12 How-ever, there have been minimal recent popu-lation-based data evaluating trends in BSI,and it is unclear which populations are athighest risk for BSI due to different organ-isms. Such data are necessary for targetingtreatmentandprevention efforts.We,there-fore,conducteda retrospective, population-based, cohortstudyto evaluate age- andsex-associated trends in the incidence of BSI ina geographically defined population.

METHODS

STUDY SETTING

Olmsted County is located in southeastern Min-nesota and has population characteristics simi-lar to those of US non-Hispanic whites.13 Thepopulation according to the 2000 census was124 277. There is a low prevalence of intrave-nous drug abuse.14 The Rochester Epidemiol-ogy Project is a medicalrecord linkage systemthatindexes medical records from all individu-

Author Affiliations: Divisionsof Infectious Diseases(Drs Uslan, Steckelberg, Wilson, and Baddour) andPrimary Care Internal Medicine

(Dr Crane), Department of Medicine, Division of Microbiology, Department of Pathology (Dr Cockerill), andDepartment of Health SciencesResearch (Dr St. Sauver), MayoClinic College of Medicine,Rochester, Minn. Dr Uslan isnow with the Division of Infectious Diseases, DavidGeffen School of Medicine atUCLA, Los Angeles, Calif.

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als seen by a health care provider and residing in OlmstedCounty. A single dossier existsfor eachpatient,into which medi-cal diagnoses, surgical interventions, and other key informa-tion from medical records are regularly abstracted and en-tered into computerized indexes using the   InternationalClassification of Diseases, Ninth Revision, Clinical Modifica-tion.13,15 The Rochester Epidemiology Project provides accessto all inpatient, outpatient, emergency department, and nurs-ing home records of county residents, regardless of provider,allowing for accurate population-based incidence studiesof dis-ease causes and outcomes.13

CASE ASCERTAINMENT

Casesof BSIwereidentified viacomputerizeddatabases frombothmicrobiology laboratories in Olmsted County: Mayo Clinic andOlmsted Medical Center. All positive blood culture results iden-tified betweenJanuary 1, 2003, andDecember 31, 2005, werein-cluded. The BSIs were classified as nosocomial, health care asso-ciated, or community acquired.16 The Mayo Clinic uses anautomated blood culture system (BACTEC 9240) and aerobic(Plus/10 Aerobic/F) and anaerobic (Lytic/10 Anaerobic/F) cul-ture vials, and Olmsted Medical Center also uses an automatedblood culture system (BACTEC 9050) and aerobic (Standard/10Aerobic/F) and anaerobic (Anaerobic/F) culture vials (BD Bio-

sciences, San Jose, Calif). Blood cultures were identified usingstandardmicrobiology techniques accordingto the Clinical Labo-ratory Standards Institute. Both laboratories are certified by theCollege of American Pathologists. There were no significantchanges in culture techniques during thestudy period. Themedi-cal records of allcases of BSI were manually reviewed by the pri-mary investigator (D.Z.U.) to confirm the diagnosis and resi-dency status. Anycases of BSI judged problematic werereviewedwithan experiencedinfectiousdiseases investigator(L.M.B.).Non-residency in Olmsted County at the time of BSI was an exclusioncriterion. Patients were followed up from the date of BSI throughtheir most recent health care encounter, as documented in theRochester Epidemiology Project database.

Given that contaminated blood cultures may represent upto half of all positive blood culture results,17-20 we used the defi-nition of contamination as previously described by Bekeris et

al.21 A blood culture was considered to be “contaminated” if 1or more of the following were identified in only 1 bottle: co-agulase-negative staphylococcal species, Propionibacterium ac-nes, Micrococcus species, viridans group streptococci, Coryne-bacterium species, or Bacillus species.

DATA ANALYSIS

Incidence rates of BSI were derived using cases of BSI as thenumerator and assuming that the entire Olmsted County popu-lationbetween 2003 and2005 wasat risk of infection. The de-nominator wasinterpolated from the 2000 Olmsted County cen-sus figures, using an annual projected population growth rateof 1.9% per year. Incidence rates were directly adjusted to the

age distribution of the US white 2000 population.

22

Only ini-tial episodes of BSI were included as incident cases. For pa-tientswith multiple events, incidence rates were calculated basedon the first event only. Deaths were confirmed via Minnesotaelectronic death certificate data, and 95% confidence intervals(CIs) around the point estimates were calculatedassumingthatincident cases followed a Poisson error distribution. Differ-ences in means between multiplegroups were tested with1-wayanalysis of variance. Cox proportional hazards modeling wasused to examine the association between organism and sur-vival while adjusting for age and sex. The level of significancefor all statistical tests was 2-sided, with.05.All analyseswere

conducted using computer software (JMP software, version6.0.0; SAS Institute Inc, Cary, NC). The institutional reviewboards of Mayo Clinic and Olmsted Medical Center approvedthe study.

RESULTS

A total of 1051 unique patients with positive blood cul-ture results between January 1, 2003, and December 31,2005, were identified. Of these patients, 401 (38.2%) hadpositive blood culture results that met the definition of contamination. Of the contaminants, 286 (71.3%) werecoagulase-negative staphylococci, 29 (7.2%) were Cory-nebacterium  species, 18 (4.5%) were   Micrococcus  spe-cies, and 12 (3.0%) were Propionibacterium acnes. A totalof 650 patientshadpositive blood culture results that weredeemed clinically relevant, and were included as inci-dent cases.Multiple BSIs were notedin 29 patients(4.5%).The mean±SD age of the cases was 63.1±23.1 years, and52.5% were male. Of the cases, 64 (9.8%) were non-white, reflecting the general demographic characteris-tics of southeastern Minnesota. A total of 188 cases(28.9%) occurred in patients older than 80 years. Caus-ative organisms by epidemiologic category are shown inTable 1. The 2 most common causative organisms over-all were Escherichia coli  (163 BSIs [25.1%]) and  S au-reus (108 BSIs [16.6%]).

Of the BSIs, 124(19.1%) were nosocomial, 237(36.5%)were health care associated, and 289 (44.5%) were com-munity acquired. Males were more likely to have noso-comial BSIs than females (Figure 1). Females had 43nosocomial BSIs(13.9%),112 health care–associated BSIs(36.2%), and 154 community-acquired BSIs (49.8%),compared with 81 nosocomial BSIs (23.8%), 125 healthcare–associated BSIs (36.7%), and 135 community-acquired BSIs (39.6%) for males (P =.002).

Age- and sex-specific incidence rates are shown inTable 2. The annual incidence of BSIs during the studyperiod, age and sex adjusted to the US white 2000 cen-sus, was 189 (95% CI, 174-204) per 100 000 person-years.The age-adjusted incidence rates were 156 for females(95% CI, 138-174) and 237 for males (95% CI, 211-263) (P.001). The incidence rate of BSIs in the eldestpatients (80 years) was 1455 (95% CI, 1268-1691) per100 000 person-years—more than 3 times greater thanthe incidencerate among thenext oldestagegroup(60-79year olds). In addition, the incidence rate in males in thisgroup (rate, 2149; 95% CI, 1695-2603) was almost twicethat of females (rate, 1143; 95% CI, 922-1366) (P.001).Incidence rates increased with age across both sexes, but

males hadsubstantially higher incidence rates in the olderage groups (70 years) (Figure 2).To further investigate sex-associated differences in pa-

tients with BSIs, we compared rates of BSI due to gram-positive cocci vs those due to gram-negative bacilli. Therewere 321 total gram-positive BSIs (49.8%), 281 gram-negative BSIs (43.6%), and 43 polymicrobial BSIs (6.7%).The mean age among those with polymicrobial BSIs (71.5years; 95% CI, 64.6-78.5 years) was greater than amongthose with gram-positive BSIs (61.8 years; 95% CI, 59.3-64.4 years) or gram-negative BSIs (63.1 years; 95% CI,

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60.4-65.8 years) (P =.03). The overall incidence of gram-positive BSIs was 64 (95% CI, 53-75) per 100 000 person-years for females and 133 (95% CI, 112-153) per 100 000person-years for males (P.001). Gram-negative BSI in-cidence was 85 (95% CI, 72-98) per 100 000 person-years for females and 79 (95% CI, 64-95) per 100 000person-years for males (P =.79). Age- and sex-

associated trends in the incidence of gram-positive vsgram-negative BSI are shown in  Figure 3. For  E coli,the age-adjusted incidence rate was 61 (95% CI,50-72) per 100 000 person-years for females and 32(95% CI, 22-42) per 100 000 person-years for males(P =.002); the age- and sex-adjusted rate was 48 (95%CI, 41-55) per 100 000. The overall age-adjusted inci-dence rate (per 100 000 person-years) for S aureus was23 (95% CI, 16-30) for females and 46 (95% CI,34-57) for males (P =.005); the age- and sex-adjustedrate was 32 (95% CI, 26-39) per 100 000 person-years.

There was a similar difference in rates of BSIs due toviridans group streptococci, 25 (of 35, or 71.4%) of which were in males (incidence, 16/100000 person-years for males and 5/100 000 person-years forfemales;  P =.01). Comparisons of incidence rates bysex for the 6 most common organisms are shown inFigure 4.

The median duration of follow-up after BSI was 329days (interquartile range, 94-668 days). Eighty-eight in-dividuals died during the initial hospitalization (crudemortality, 13.5%). There wasno overall difference in mor-tality by sex (hazard ratio for males, 1.07; 95% CI, 0.68-1.70; P =.76). The hazard ratio for death correspondingto a 10-year increase in age was 1.18 (95% CI, 1.06-1.32; P =.002). The age-adjusted hazard ratio for death

due to nosocomial BSI was 4.64 (95% CI, 2.52-8.80;P.001).

COMMENT

In our geographically defined population, the incidenceof BSI increased sharply with age. Bloodstream infec-tion due to E coli was far more common in females, likelyreflecting the propensity for urinary tract infections, in-cluding pyelonephritis, in females. There were markeddifferences in the rates of S aureus BSI between males andfemales, with rates in males almost double those in fe-males in some age groups. A similar difference was noted

with viridans group streptococci.The difference in sex-specific incidence rates is strik-ing. Reasons for the increased frequency of BSI due togram-positive cocci in males seem directly related to theincreased number of nosocomial BSIs in males. In-creased intravenous drug abuse among males seems anunlikely explanation, given that most cases were in el-derly persons and given the low prevalence of intrave-nous drug abuse in Olmsted County.14 It is tempting tospeculate that this proclivity among older males for BSIsdue to gram-positive cocci may explain, in part, the ob-

Table 1. Rank Order of Microorganisms in 650 BSIs, 2003 to 2005, in Olmsted County, Minnesota

RankTotal

(N = 650)Nosocomial

(n = 124)Health Care Associated

(n = 237)Community Acquired

(n = 289)

1   Escherichia coli S aureus E coli E coli  

2   Staphylococcus aureus    Coagulase-negative staphylococci   S aureus S aureus  

3 Coagulase-negative staphylococci   E coli    -Hemolytic streptococci   Klebsiella  species

4   Klebsiella  species   Enterococcus  species Coagulase-negative staphylococci   -Hemolytic streptococci

5   -Hemolytic streptococci   Klebsiella  species   Klebsiella  species Viridans group streptococci

6 Polymicrobial (2 organisms)*   Pseudomonas  species Polymicrobial   S pneumoniae 

7 Viridans group streptococci   Candida  species   Enterococcus  species Polymicrobial

8   Streptococcus pneumoniae    Anaerobe Viridans group streptococci Coagulase-negative staphylococci

9   Enterococcus  species Polymicrobial   S pneumoniae    Anaerobe

10 Anaerobe   -Hemolytic streptococci   Pseudomonas  species   Enterococcus  species

11   Pseudomonas  species Viridans group streptococci Anaerobe   Pseudomonas  species

12   Candida  species   S pneumoniae Candida   species   Candida  species

13 Other† Other Other Other

Abbreviation: BSI, bloodstream infection.*Polymicrobial BSIs are counted with their respective organisms.†Includes Citrobacter freundii , Enterobacter cloacae , Salmonella  (nontyphi), Proteus  species, Acinetobacter  species, Haemophilus influenzae , Serratia marcescens ,

Moraxella  species, Stenotrophomonas maltophilia , Prevotella  species, Neisseria meningitidis , and Lactobacillus  species (all 5 BSIs).

100

50

70

90

80

60

40

20

30

10

0

    %    o

    f    B    S    I   s

Female

13.9

36.2

49.8

Male

23.8

36.7

39.6

Sex

CA HCA No socomial

Figure 1. Distribution of the 650 bloodstream infections (BSIs) by healthcare exposure category. CA indicates community acquired; and HCA, healthcare associated. Percentages may not total 100 due to rounding.

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servation that IE predominantly affects older males.23-27

The incidence rates of IE in a population-based settinghave been previously described, with an age- and sex-adjusted rate of 4.9per 100 000 person-years.14,23 The in-cident rate ratio for male vs female sex was 2.5:1.0.14

Recent series of patients, from the International Collabo-ration on Endocarditis, with IE due to S aureus reportedthat 60% to 70% were male.28,29 In our study, the rate of S aureus BSIs in males was twice that in females. The sexdiscrepancy in IE cases could be explained by differ-ences in underlying rates of BSI. This is a novel obser-vation that deserves further investigation.

Data derived from population-based studies for BSI inthe United States were not previously available. The inci-dence of BSI in our study (190 per 100 000 person-years)exceeds that of prior estimated incidence rates of BSI fromEurope from the 1980s and 1990s (76.5 and 153 per100 000).8,9 It is unclear if this is because of a true increasein the rates of BSI overall, changes in blood culture tech-niques resulting in detection bias, or differing populationdemographics in the varying regions studied.

Therank order of microorganisms defined in our studywassimilar to that reported previously.20,30,31 In our popu-lation-based study,  E coli  remained the most commoncausative organism, followed by S aureus. These trendsfor organisms isolated are similar to a recent large se-ries4 of BSIs from the United Kingdom, which also re-ported E coli and  S aureus as the most common organ-isms isolated. A recent analysis32 of 24 179 cases of nosocomial BSIs in US hospitalsfound that the most com-mon organisms were coagulase-negative staphylococci,S aureus, enterococci, and Candida  species. We specu-

late that the difference in rank order of microorganismsseen in our study is because of the inclusion of commu-

nity-acquired and health care–associated BSIs.Our study has several limitations. We used a set defi-nition of blood culture contamination to avoid ascer-tainment biasin retrospectively identifying incident cases.However, as noted by Bekeris et al,21 isolates classifiedas contaminants using this study definition could still bereflective of clinical infection. Prior studies31,33 of BSIs withcoagulase-negative staphylococci have suggested that ap-proximately 25% to 30% of isolates were considered tobe pathogens. In our study, there were 58 clinically sig-nificant coagulase-negative staphylococcal BSIs (16.9%)

Table 2. Age- and Sex-Specific Annual Incidence Rates of BSI per 100 000, in 650 Patients in Olmsted County, Minnesota,2003 to 2005*

Type of Infection

Age Group, y

Total†0-18 19-39 40-59 60-79   80

Escherichia coli 

Female 5.4 (3) 26.2 (16) 47.5 (26) 161.4 (39) 403.6 (36) 61.5 (120)

Male 1.7 (1) 10.0 (6) 11.6 (6) 101.4 (21) 249.9 (10) 31.1 (44)

Total 3.5 (4) 18.2 (22) 29.9 (32) 133.7 (60) 356.0 (46) 47.7 (164)

Staphylococcus aureus Female 1.8 (1) 0 18.3 (10) 78.7 (19) 145.8 (13) 22.7 (43)

Male 10.3 (6) 5.0 (3) 30.8 (16) 111.0 (23) 424.8 (17) 45.3 (65)

Total 6.1 (7) 2.5 (3) 24.4 (26) 93.6 (42) 232.2 (30) 32.0 (108)

Gram-positive cocci

Female 14.4 (8) 21.3 (13) 40.2 (22) 169.7 (41) 470.9 (42) 64.1 (124)

Male 29.1 (17) 23.4 (14) 100.2 (52) 318.5 (66) 1149.5 (46) 133.1 (188)

Total 21.9 (25) 22.4 (27) 69.4 (74) 238.4 (107) 681.1 (88) 93.2 (321)

Gram-negative bacilli

Female 9.0 (5) 36.0 (22) 80.3 (44) 186.2 (45) 594.2 (53) 85.3 (161)

Male 8.6 (5) 20.1 (12) 50.1 (26) 188.2 (39) 749.7 (30) 78.5 (111)

Total 8.8 (10) 28.2 (34) 65.6 (70) 187.2 (84) 642.4 (83) 80.9 (281)

All BSIs

Female 23.5 (13) 58.9 (36) 124.1 (68) 372.5 (90) 1143.7 (102) 156.4 (309)

Male 37.6 (22) 46.9 (28) 158.0 (82) 593.6 (123) 2149.1 (86) 237.3 (341)

Total 30.7 (35) 52.9 (64) 140.6 (150) 474.6 (213) 1455.0 (188) 188.9 (650)

Abbreviation: See Table 1.*Data are given as incidence per 100 000 person-years. Total numbers in each age group include polymicrobial BSIs and Candida  species. Numbers in

parentheses indicate the actual number of BSI cases.†Total rates by sex are age adjusted, and overall total rates are age and sex adjusted to the US white 2000 census.

3500

2500

2000

3000

1500

1000

500

0

Age, y

    I   n   c    i    d   e   n   c   e    R   a   t   e   p   e   r    1    0    0    0    0    0    P   e   r   s   o   n  -    Y   e   a   r   s

  Male

Female

0 10 20 30 40 50 60 70 80 90

Figure 2. Incidence rates of bloodstream infection by age, from January 1,2003, to December 31, 2005, in Olmsted County, Minnesota.

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of 344 positive blood culture results for this organism.Our results may, therefore, underestimate the true inci-dence of BSIs due to this organism.

Another limitation is that Olmsted County is a rela-tively homogeneous population in regard to racial andethnic composition, with a low prevalence of intrave-nous drug abuse. Therefore, the generalizability of our

study’s findings to groups underrepresented in the popu-lation could be limited. However, as previously noted,the characteristics of the Olmsted County population aresimilar to those of other US whites, with the exceptionof slightly higher income and education levels, and stud-ies in Olmsted County can be extrapolated to a large partof the general population.13 Presumably, an increasedprevalence of intravenous drug abuse would result in anincrease in the incidence of BSI in younger age groups.

Last, it is possible that residents of thepopulation couldhave been examined and diagnosed as having BSI at aninstitution outside of Olmsted County, although the geo-graphic isolation of Olmsted County from other urbancenters makes this unlikely.13,23 Only patients with BSIdetected via positive blood culture result were includedas incident cases; therefore, patients with BSIs who didnot have blood cultures drawn (ie, did not seek medicalattention or were treated empirically without cultures)would have been missed. Patients who received antimi-crobial therapy prior to cultures being obtained may havefalsely negative cultures. Our results, then, would be anunderestimate of the true incidence of BSIs. It is diffi-cult to know what impact, if any, this would have on age-

and sex-specific incidence rates.The primary strength of the study is that through useof the Rochester Epidemiology Project we were able tostudy incidence of BSI in a large population without thereferral bias seen with single-institution studies of BSI.14

The essentially complete ascertainment of all BSI casesin our study for a population of known size, age, and sexdistribution allows an unbiased and accurate estimationof incidence rates.

In conclusion, our data indicate that there are strik-ing sex-associated differences in organism distributionamong patients with BSI. Escherichia coli BSI was morecommon in females, and BSI due to  S aureus  and viri-dans group streptococci wasmore commonin males. The

epidemiologic and pathogenic factors associatedwith thesesex differences deserve further investigation. In addi-tion, sex-specific BSI trends may have implications forempirical antimicrobial therapy in patients with pre-

1600

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0

    I   n   c    i    d   e   n   c   e    R   a   t   e   p   e   r    1    0    0    0    0    0    P   e   r   s   o   n  -    Y   e   a   r   s

  Male

Female

A

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0

Age, y

    I   n   c    i    d   e   n   c   e    R   a   t   e   p   e   r    1    0    0    0    0    0    P   e   r   s   o   n  -    Y   e   a   r   s

0 10 20 30 40 50 60 70 80 90

B

Figure 3. Incidence rates of gram-positive cocci (A) and gram-negativebacilli (B) bloodstream infections by age, from January 1, 2003, to December31, 2005, in Olmsted County, Minnesota.

Viridans GroupStreptococci

80

60

70

50

30

20

40

10

0   Escherichia coli 

Staphylococcus aureus 

Coagulase-Negative

Staphylococci

Klebsiella Species 

β-HemolyticStreptococci

Organism

    I   n   c    i    d   e   n   c

   e    R   a   t   e   p   e   r    1    0    0    0    0    0    P   e   r   s   o   n  -    Y   e   a   r   s

  Male

Female

Figure 4. Incidence rates of the 6 most commonly isolated microorganisms in 650 patients by sex, from January 1, 2003, to December 31, 2005, in OlmstedCounty, Minnesota. Error bars represent 95% confidence intervals calculated around the point estimate, assuming incident cases follow a Poisson errordistribution. P  values for comparisons by sex for each organism are as follows:  Escherichia coli , P =.002; Staphylococcus aureus , P =.005; coagulase-negativestaphylococci, P =.10; Klebsiella  species, P =.07; -hemolytic streptococci, P =.60; and viridans group streptococci,  P =.01.

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sumed BSI, especially as rates of antimicrobial resis-tance increase. Further research on specific sex-associated risk factors for BSI is needed to clarify thesetrends.

Accepted for Publication: December 26, 2006.Correspondence: Daniel Z. Uslan, MD, Division of In-fectious Diseases, David Geffen School of Medicine atUCLA, 10833 LeConte Ave, 37-121 CHS, Los Angeles,CA 90095 ([email protected]).Author Contributions: Dr Uslan had full access to all of the data in the study and takes responsibility for the in-tegrity of the data and the accuracy of the data analysis.Study concept and design:  Uslan, Crane, Steckelberg,Cockerill, St. Sauver, and Baddour. Acquisition of data:Uslan and Cockerill. Analysis and interpretation of data:Uslan, Steckelberg, Cockerill, St. Sauver, Wilson, andBaddour. Drafting of the manuscript: Uslan and St. Sauver.Critical revision of the manuscript for important intellec-tual content: Uslan, Crane, Steckelberg, Cockerill, St.Sauver, Wilson, and Baddour. Statistical analysis: Uslan.Obtained funding: Steckelberg and Baddour. Administra-tive, technical, and material support: Crane, Steckelberg, Wilson, and Baddour.  Study supervision:   Steckelberg,Cockerill, Wilson, and Baddour.  Epidemiologic exper-tise: St. Sauver.Financial Disclosure: None reported.Previous Presentation: This study was presented in partat the Infectious Diseases Societyof AmericaAnnual Meet-ing; October 15, 2006; Toronto, Ontario.Acknowledgment: We thank Imad Tleyjeh, MD, for as-sistance with the study design; Emily Vetter and BarbaraYawn, MD, for assistance in obtaining microbiology rec-ords; and Kathy Parsons for administrative support.

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