The role of diabetes mellitus in patients with bloodstream infections

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1 Originl rticle Peer reviewed rticle SWISS MED WKLY 2008;138(35 36): The role of dietes mellitus in ptients with loodstrem infections M. Stoeckle, C. Kech, A. Trmpuz, W. Zimmerli Bsel University Medicl Clinic, Liestl, Switzerlnd Clinic of Infectious Diseses nd Hospitl Epidemiology, University Hospitl Bsel, Switzerlnd Summry Bckground: Since dietes mellitus predisposes to infection, we evluted whether dietes increses the risk of loodstrem infection nd worsens its outcome. Methods: During 4-yer period 71 dietic nd 252 non-dietic ptients with loodstrem infection were included. Risk fctors for deth were ssessed y univrite nd multivrite nlysis. Results: Bloodstrem infection ws more frequent in dietics thn in non-dietics (25.8/1000 dmissions vs. 5.8/1000 dmissions, p <0.0001). Urinry trct infection ws the predominnt source, nd Escherichi coli the most frequent microorgnism in oth groups. Klesiell pneumonie ws more frequent in dietics thn in non-dietics (18% vs 5%, p <0.001). Wheres sepsis of unknown origin ws more common in dietics (14% vs. 6%, p <0.05), ctheter-relted loodstrem infection predominted in non-dietics (3% vs 10%, p <0.05). Secondry septic foci (p <0.05) nd disseminted intrvsculr cogultion (p <0.05) were more frequent in dietics. The in-hospitl mortlity rte ws similr in the two groups (18% vs. 14%). Univrite nlysis (RR [CI 95%]) in dietics reveled glycemi >20 mmol/l (3.9 [1.7 22]), ICU sty (7.1 [2 25]), mechnicl ventiltion (8.4 [1.2 57]) nd chronic renl/heptic filure (8.2 [1.6 43]) s significnt risk fctors. Hyperglycemi (4.3 [ ]) nd ICU sty (3.3 [ ]) remined significnt in multivrite nlysis. Conclusions: Dietics hd 4.4-fold higher risk of loodstrem infection, were more prone to sepsis of unknown origin nd hd more septic complictions thn non-dietics. The mortlity rte ws similr in the two groups. Key words: dietes mellitus; loodstrem infection; sepsis; outcome; Klesiell pneumonie No finncil support from ny source. Introduction It is dogm tht ptients with dietes mellitus re t incresed risk of infection or deth ssocited with n infection [1 4]. However, clinicl studies do not consistently support dietes s risk fctor for infectious complictions (including deth) [5 10]. In recent study on S. ureus cteremi, ptients with dietes were overrepresented (25%) ut dietes mellitus ws not prognostic fctor for poor outcome [9]. Risk of infection depends on severl fctors, including host defence mechnisms, functionl or ntomicl normlities of the host, nd the type, inoculum nd virulence of the infecting microorgnism. Outcome of infection is determined not only y host defence, ut lso y the timing nd ppropriteness of ntimicroil tretment. According to recently pulished lrge prospective cohort study, dietic ptients re t incresed risk of urinry trct infections, lower respirtory trct infections nd skin/soft tissue infections, compred to control group of ptients with hypertension [10]. It hs een hypothesised tht the incresed susceptiility of dietic ptients to infection my e due to impired host defense mechnisms. However, impired host defense hs een shown exclusively in dietic ptients with poor glucose control, especilly ketocidosis. These defects include impired function of polymorphonucler leukocytes nd decresed serum levels of complement fctor C4 nd zinc, s well s n impired cytokine response nd lymphocyte trnsformtion fter stimultion [1, 11 17]. In ddition to impired host defence mechnisms, other fctors my increse dietic ptients susceptiility to infection [15]. Micro - ngiopthy impirs leukocyte migrtion y thicken ing of the cpillry sement memrne, nd

2 SWISS MED WKLY 2008;138(35 36): mcrongiopthy fvours crl skin nd soft tissue infection s well s foot osteomyelitis. Autonomous neuropthy results in n incresed residul urine volume of the ldder which fvours urinry trct infection. Dietic ptients re lso t incresed risk of colonistion with Stphylococcus ureus [18], resulting in higher rte of skin nd soft tissue infection nd of S. ureus sepsis [9, 19, 20]. In ddition, dietes is risk fctor for group A nd B streptococcl disese [5, 6], cteremi due to Enteroctericee [21], pyogenic liver scess [22] nd metsttic infection from pyogenic liver scesses [23]. However, no recent dt is ville on the influence of dietes mellitus on the incidence nd outcome of loodstrem infections in generl. In the present study we nlysed ll loodstrem infections in hospitlised ptients with or without dietes mellitus, to determine whether dietes mellitus is ssocited with incresed susceptiility to loodstrem infection nd in - fluences its outcome, to evlute differences etween the two groups regrding the type of primry focus nd microorgnism, nd to ssess whether the qulity of the metolic control influences prognosis. Methods Study type nd loction This retrospective cross-sectionl study ws performed t the Bsel University Medicl Clinic Liestl, Switzerlnd. This is 400-ed teching hospitl with 11,000 12,700 dult dmissions per yer nd includes clinics for medicine (including oncology), generl surgery (no urn unit, trnsplnttions or crdic surgery), urology, orthopedic surgery, er, nose nd throt nd gynecology. Study popultion nd definitions Episodes with positive lood cultures collected during 4-yer period ( ) were identified y the Centrl Lortory for Microiology, followed y hospitl chrt review of ll hospitlised ptients ged 16 yers or over with t lest one positive lood culture. Ptients with true loodstrem infection, defined s 01 positive lood culture with cliniclly plusile microorgnism nd 02 criteri of the systemic inflmmtory response syndrome (SIRS) were included. Fulfilment of SIRS criteri ws not required in ptients with positive lood culture nd concomitnt isoltion of the sme microorgnism from n infectious focus. Where there ws positive lood culture with microorgnism of low virulence, such s cogulse-negtive stphylococci, Propionicterium spp., Corynecterium spp. or Bcillus spp., two seprte positive lood cultures with the sme microorgnism nd t lest two SIRS criteri were required. A new episode of loodstrem infection ws defined s positive lood cultures >3 months prt. Ptients were excluded from the study if the microorgnisms isolted in lood cultures were considered contminnts (ccording to the ove definition), if they were not treted in our institution, their chrts were not ville, no ntimicroil therpy ws dministered or the result of the first positive lood culture ws ville only fter deth. A ptient ws clssified s dietic under the following conditions: () dignosis of dietes previous to the index hospitlistion, or () dignosis estlished during hospitlistion ccording to interntionl stndrds nd dischrge with the dignosis of dietes mellitus. Ptients exclusively with high lood glucose vlues during cute infection were not clssified s hving dietes. Specimen collection nd processing During ferile episode t lest two sets of lood culture pirs were otined, ech pir consisting of n eroic nd n neroic ottle. Blood culture ottles were incuted in the BACTEC 9240 lood culture system (Becton Dickinson, Sprks, Md.) for t lest five dys t 35 C. Identifiction of microorgnisms nd ntiiotic susceptiility testing were done ccording to stndrd lortory operting procedures. Dt collection Ptients with loodstrem infection were clssified s dietics or non-dietics ccording to stndrd definitions y the dmitting physicin. The ptient s ge, sex, underlying conditions, nd predisposing fctors for sepsis were recorded. In dietic ptients the type nd durtion of dietes, tretment nd HA1c (mesured during the index hospitlistion, or the most recent vlue from the referring physicin) were noted. Bloodstrem infections were clssified into community-cquired nd nosocomil infections. The source of sepsis, the custive microorgnism(s) isolted from lood nd if possile from suspected primry source, nd the ntimicroil therpy (type of drug, dily dose, mode of dministrtion), efore nd fter receiving the microiology result, were recorded. The following clinicl nd lortory prmeters were recorded t the time of the the initil dignosis of loodstrem infection: systolic lood pressure, hert rte, ody temperture, lood leukocyte count (totl leukocytes nd percentge of nd forms), C-rective protein, nd lood glucose level. The following outcome criteri were recorded: occurrence of complictions such s septic shock, cute renl or heptic filure, disseminted intrvsculr cogultion nd secondry foci. Also documented were dmission to the intensive cre unit, need for mechnicl ventiltion, length of sepsis-relted hospitl sty, trnsfer to other institutions nd deth. Dt nlysis We compred demogrphic dt, underlying conditions, predisposing fctors for sepsis, source of loodstrem infection, custive microorgnisms, nd clinicl nd lortory prmeters in septic ptients with nd without dietes. To determine whether dietes is ssocited with complicted course or deth due to sepsis, we compred dietic nd non-dietic ptients with respect to rte of complictions, rte nd durtion of ICU sty, length of hospitl sty due to the septic episode, survivors outcome (dischrge / trnsfer to nother institution) nd sepsis-relted mortlity rte. To estimte the role of metolic control we compred complictions nd

3 Bloodstrem infection nd dietes mellitus 514 outcome etween well controlled nd poorly controlled dietic ptients, using HA1c s the prmeter of qulity of metolic control. Since cute infection my led to incresed lood glucose levels, rndom or fsting lood glucose levels t dmission were not used to discriminte etween well nd poorly controlled dietic ptients. To evlute differences etween groups, the unpired Student s t-test for normlly distriuted continuous vriles nd the Mntel-Henszel chi-squre test or two-tiled Fisher s exct test for ctegoricl vriles ws used. Prmeters found to e of orderline sttisticl significnce (P <0.1) y univrite nlyses or with iologicl plusiility were further nlysed y step-wise logistic regression model (sttisticl pckge SPSS 10.0 for Windows, SPSS, Chicgo, IL, USA). A p vlue <0.05 ws considered significnt (two-tiled). Results Demogrphy nd site of infection During the 4-yer study period, 45,850 dult ptients were dmitted to the hospitl. Among them, pproximtely 6% hd, ccording to the referring physicin, dignosis of dietes mellitus prior to dmission. During the study period 449 episodes of positive lood cultures were recorded in the cteriology lortory. 126 (28.1%) of these episodes were excluded ccording to the exclusion criteri (79 microorgnisms in lood culture were considered s contmintion, 30 episodes were not treted t our hospitl, 10 chrts were not ville, 5 preterminl ptients received no ntiiotics, nd in three episodes the lood culture result ws received only post mortem). Tle 1 summrises the chrcteristics of the study popultion. We oserved 71 episodes of loodstrem infection in 2,750 ptients with dietes (25.8 episodes / 1000 dmissions), nd 252 in 43,100 ptients without dietes (5.8 episodes / 1000 dmissions). Thus the reltive frequency of loodstrem infection ws >4 times higher in dietic thn in non-dietic ptients (<0.0001). The medin ge ws similr (74 vs. 70 yers). The frction of nosocomil loodstrem infections did not differ etween the groups. Urinry trct infection ws the most frequent origin of cteremi, occurring in pproximtely one third of the ptients in oth groups, followed y dominl nd lower respirtory trct infection. Regrding the reltive frequency of the origin of cteremi there were only two significnt differences etween the two groups. In dietic ptients the focus of infection remined undetermined 2.2 times more often thn in non-dietics, wheres in non-dietic p- Tle 1 Demogrphics nd source of loodstrem infection in 71 dietic nd 252 non-dietic ptients. Chrcteristic Dietics Non-dietics p (n = 71) (n = 252) No. dmissions with chrcteristic ,100 No. episodes of cteremi / 1000 dmissions < Medin ge (rnge) 74 (43-92) 70 (18-96) Mle sex 38 (53.5%) 133 (52.8%) Type of dietes Type 1 2 (2.8%) n.. Type 2, controlled with diet only 18 (25.4%) n.. Type 2, orl ntidietic drugs 33 (46.5%) n.. Type 2, insulin tretment 14 (19.7%) n.. Secondry dietes 4 (5.6%) n.. Men durtion of dietes in yers (rnge) 5 (0 40) n.. HA1c (rnge) 7.9% (5 14.8) n.. Nosocomil infection 20 (28.2%) 89 (35.5%) Primry site of infection: Unknown 10 (14.3%) 16 (6.3%) Urinry trct 22 (31.4%) 85 (33.7%) Lower respirtory trct 8 (11.4%) 36 (14.3%) Adominl 12 (16.9%) 35 (13.9%) Skin 2 (2.9%) 14 (5.6%) Bone/joint 4 (5.7%) 6 (2.4%) Surgicl site 7 (10%) 13 (5.2%) Intrvenous ctheter 2 (2.9%) 26 (10.3%) Hert vlve 2 (2.9%) 13 (5.2%) Other 1 (1.4%) 8 (3.2%) NOTE. Dt re no. (%) unless otherwise indicted. n.. = not pplicle

4 SWISS MED WKLY 2008;138(35 36): tients, iv-ctheter ssocited infection ws 3.6 times more frequent thn in dietics. Underlying conditions nd comoridities Tle 2 summrises the underlying conditions. Significntly fewer dietic thn non-dietic ptients hd no underlying conditions (2.8% vs. 23.0%; p = 0.001). Hypertension ws the most frequent comoridity in oth groups, ut ws still 1.8 times more frequent in dietics (54.9% vs. 30.6%; P = 0.001). The other two significnt differences were peripherl rteril occlusive disese, which ws 2.8 times more frequent (15.5% vs. 5.6%; p = 0.006), nd neuropthy, 5.8 times more frequent in dietic thn non-dietic ptients (25.4% vs. 4.4%; p <0.001). Interestingly, there ws no significnt difference etween the two groups in the prevlence of renl filure. Microorgnisms Tle 3 shows the most common microorgnisms isolted from lood cultures in the two groups. Escherichi coli (28.2% vs. 37.3%; p = 0.156) nd S. ureus (23.9% vs. 15.9%; p = 0.117) were the most frequent isoltes in oth groups. Klesiell pneumonie ws 3.5 times more prevlent Tle 2 Underlying conditions. Vrile Dietics Non-dietics (n = 71) (n = 252) p None 2 (2.8%) 58 (23.0%) Hypertension 39 (54.9%) 77 (30.6%) Congestive hert filure 3 (4.2%) 16 (6.3%) Hert vlve disese 4 (5.6%) 20 (7.9%) Ischemic hert disese 18 (25.4%) 43 (17.1%) Peripherl rteril ostructive disese 11 (15.5%) 14 (5.6%) Stroke 8 (11.3%) 15 (6.0%) Neuropthy 18 (25.4%) 11 (4.4%) <0.001 Chronic renl filure 5 (7.0%) 11 (4.4%) Chronic heptic filure 2 (2.8%) 6 (2.4%) Chronic ostructive lung disese 5 (7.0%) 26 (10.3%) Solid orgn mlignncy (not in remission) 11 (15.5%) 33 (13.1%) Hemtologicl mlignncy (not in remission) 3 (4.2%) 13 (5.2%) Neutropeni 1 (1.4%) 2 (0.8%) Humorl immunodeficiency 1 (1.4%) 8 (3.2%) Cellulr immunodeficiency 8 (11.3%) 24 (9.5%) Smoking 16 (22.5%) 72 (28.6%) Alcohol use 4 (5.6%) 20 (7.9%) Intrvsculr drug use 0 5 (2.0%) Others 4 (5.6%) 6 (2.4%) NOTE. Dt re no. (%). Humorl immunodeficiency: HIV infection ny stge, chronic lymphtic leukemi, lymphom, multiple myelom, uremi, nephrotic syndrome, splenectomy. Cellulr immunodeficiency: HIV infection A3-C3, corticosteroids (>25 mg/d prednisone for t lest one month or 700 mg cumultive dose), other immunosuppressive drugs, trnsplnttion. Tle 3 Microorgnisms isolted from lood cultures. Microorgnism Dietics Non-dietics (n = 71) (n = 252) p Escherichi coli 20 (28.2%) 94 (37.3%) Stphylococcus ureus 17 (23.9%) 40 (15.9%) Klesiell pneumonie 13 (18.3%) 13 (5.2%) <0.001 Streptococcus pneumonie 6 (8.5%) 31 (12.3%) Enterococcus feclis 4 (5.6%) 4 (1.6%) Cndid licns 2 (2.8%) 4 (1.6%) Klesiell oxytoc 2 (2.8%) 2 (0.8%) Bcteroides spp. 1 (1.4%) 6 (2.4%) Cogulse-negtive stphylococci 0 (0%) 12 (4.8%) Other 10 (14.1%) 59 (23.4%) Polymicroil infection 4 (5.6%) 13 (5.2%) NOTE. Dt re no. (%). 79 microorgnisms, therefore totl >100%. 265 microorgnisms, therefore totl >100%.

5 Bloodstrem infection nd dietes mellitus 516 in dietics thn in non-dietics (18.3% vs. 5.2%; p <0.001). Clinicl presenttion, complictions, outcome In the first three dys fter dignosis of loodstrem infection there ws no significnt difference regrding vitl signs etween the two groups (dt not shown). A similr frction of ptients required tretment in the ICU. As shown in Tle 4, secondry foci of infection (p = 0.04) nd disseminted intrvsculr cogultion (p = 0.030) were significntly more common in dietic thn nondietic ptients. The medin durtion of hospitl sty until dischrge or trnsfer to nother institution ws 1.6 times longer for dietics (21 nd 13 dys respectively: p <0.0001). In contrst, no difference in the medin durtion of hospitl sty ws noticed in ptients who died. Significntly more dietics required trnsfer to nother institution nd were therefore less commonly dischrged home. Mortlity ws similr etween the two groups; however, the deth rte per 1,000 dmissions ws 5.6 times higher in dietic thn non-dietic ptients. Tle 4 Complictions nd outcome. Compliction Dietics Non-dietics p (n = 71) (n = 252) None 39 (54.9%) 160 (63.5%) ICU sty 21 (29.6%) 63 (25.0%) Mechnicl ventiltion 5 (7.0%) 13 (5.2%) Secondry foci 13 (18.3%) 24 (9.5%) Septic shock 9 (12.7%) 28 (11.1%) Disseminted intrvsculr cogultion 5 (7.0%) 5 (2.0%) Acute respirtory distress syndrome 0 4 (1.6%) Acute renl filure 0 2 (0.8%) Medin durtion of hospitl sty (dys) until dischrge < until deth Dischrged home 41 (57.7%) 186 (73.8%) <0.01 trnsfer to other institution 17 (23.9%) 30 (11.9%) Mortlity rte 13 (18.3%) 36 (14.3%) 0.97 Deth rte/1,000 dmissions < NOTE. Dt re no. (%) unless otherwise indicted. Severl ptients hd more thn one (up to six) different complictions; therefore the sum of complictions exceeds 100%. Tle 5 Univrite nlysis of risk fctors for ftl outcome of loodstrem infection in 71 dietic ptients. Chrcteristic No. (%) of ftl episodes Reltive risk in presence vs. sence of chrcteristic (95% CI) Age 75 yers 6/33 (18.2%) vs. 7/38 (18.4%) 0.98 ( ) Mle sex 7/38 (18.4%) vs. 6/33 (18.2%) 1.02 ( ) HA 1c >7% 6/38 (15.8%) vs. 2/19 (10.5%) 1.59 ( ) Crdiovsculr disese 8/27 (29.6%) vs. 5/44 (11.4%) 3.28 ( ) Neuropthy 4/18 (22.2%) vs. 9/53 (17.0) 1.40 ( ) Chronic renl/heptic filure 4/7 (57.1%) vs. 9/64 (14.1%) 8.15 ( ) Mlignncy 3/14 (21.4%) vs. 10/57 (17.6%) 1.28 ( ) Smoking 4/16 (25.0%) vs. 1/12 (8.3%) 3.67 ( ) Alcoholism 1/4 (25.0%) vs. 12/67 (17.9%) 1.53 ( ) Nosocomil infection 5/20 (25%) vs. 8/51 (15.7%) 1.79 ( ) Unknown focus 3/10 (30%) vs. 10/61 (16.4%) 2.19 ( ) Urinry trct infection 2/22 (9.1%) vs. 11/49 (22.4%) 0.35 ( ) Lower respirtory trct infection 3/8 (37.5%) vs. 10/63 (15.9%) 3.18 ( ) Surgicl site infection 2/7 (28.6%) vs. 11/64 (17.2%) 1.93 ( ) Glycemi >20 mmol/l 8/20 (40%) vs. 5/50 (10%) 3.94 ( ) ICU sty 8/21 (38.1%) vs. 5/63 (7.9%) 7.14 ( ) Mechnicl ventiltion 3/5 (60%) vs. 10/66 (15.2%) 8.4 ( ) Congestive hert filure, ischemic hert disese, vlvulr hert disese, stroke, peripherl rteril occlusive disese. Dt on smoking missing in 43 ptients (mong them 8 died).

6 SWISS MED WKLY 2008;138(35 36): Fctors ssocited with deth Tle 5 shows the univrite nlysis of risk fctors for deth in dietics. Four fctors were ssocited with significntly incresed reltive risk. Among them, mechnicl ventiltion ws the most significnt risk fctor. Poor control of glycemi t the time of loodstrem infection ws ssocited with significntly incresed risk of deth, wheres poor long-term control (HA1c) did not correlte with poor prognosis. Chronic renl or heptic filure incresed the risk of deth more thn 8-fold. In the multivrite nlysis, hyperglycemi t the time of dignosis of sepsis (RR = 4.3 [ ]) nd ICU sty (RR = 3.3 [ ]) remined significnt. Tle 6 shows the univrite nlysis of risk fctors for deth in non-dietics. Six fctors were significntly more often ssocited with deth, the most importnt eing ICU sty, mechnicl ventiltion nd underlying neuropthy. In contrst, ptients with urinry trct infection s the source of cteremi hd fctor significntly less often ssocited with deth thn those with other primry foci. In the multivrite nlysis, ge 075 yers (RR = 2.9 [ ]), neuropthy (RR = 4.2 [ ]) nd ICU-sty (RR = 2.9 [ ]) remined significnt. Discussion A qurter of century go Ryfield et l. [15] showed tht 14% of ll deths in dietics were cused y infection nd tht the infection-sso - cited deth rte ws pproximtely twice s high s in non-dietic ptients. Whether the higher deth rte ws due to n incresed infection-ssocited mortlity rte or the result of higher host susceptiility to infection remined uncler. With the introduction of novel orl ntidietic drugs nd long-cting insulins the mngement of dietes mellitus nd glycemi control hs mde significnt progress. However, the effect of these novel tretment modes on susceptiility to nd outcome of infection in dietic ptients hs not yet een quntified [24 26]. It is conceivle tht dietes mellitus hs fded s risk fctor for ftl outcome of infection ecuse, thnks to improved metolic control, host defence in dietic ptients is no longer compromised. The ssocition etween dietes mellitus nd incresed susceptiility to infection is common elief supported y few dt [1]. In the lrgest nd most recent study, ptients with type 1 nd type 2 dietes mellitus were shown to e t incresed risk of lower respirtory trct infection, urinry trct infection nd skin nd mucous memrne infection compred with control hypertensives [10]. In this study dt were otined from generl prctitioners nd loodstrem infection ws not included s n outcome mesure. In our study the incidence of loodstrem infection ws evluted mong hospitlised ptients with nd without dietes nd fctors ssocited with deth. The incidence of loodstrem infection ws 4.4 times higher in ptients with dietes thn in non-dietics. This finding ws lso reported in severl previous studies, ut in our study this difference ws higher thn tht reported y Tle 6 Univrite nlysis of risk fctors for ftl outcome of loodstrem infection in 252 nondietic ptients. Chrcteristic No. (%) of ftl episodes Reltive risk in presence vs sence of chrcteristic (95% CI) Age 75 yers 23/99 (39.2%) vs. 13/153 (8.5%) 3.26 ( ) Mle sex 21/133 (15.8%) vs. 15/119 (12.6%) 1.3 ( ) ICU sty 22/63 (34.9%) vs. 14/189 (7.4%) 6.71 ( ) Mechnicl ventiltion 9/13 (69.2%) vs. 27/239 (11.3%) ( ) Nosocomil infection 19/89 (21.3%) vs. 17/163 (10.4%) 2.33 ( ) Unknown 3/16 (18.8%) vs. 33/236 (14.0%) 1.42 ( ) Urinry trct infection 2/85 (2.4%) vs. 34/167 (20.4%) 0.09 ( ) Surgicl site infection 2/13 (15.4%) vs. 34/239 (14.2%) 1.10 ( ) Crdiovsculr disese 16/78 (20.5%) vs. 20/174 (11.5%) 1.99 ( ) Neuropthy 5/11 (45.5%) vs. 31/241 (12.9%) 5.65 ( ) Chronic renl/heptic filure 4/16 (25.0%) vs. 32/236 (13.6%) 2.13 ( ) Mlignncy 13/46 (28.3%) vs. 23/206 (11.2%) 3.13 ( ) Smoking 9/72 (12.5%) vs. 7/47 (14.9%) 0.82 ( ) Alcoholism 6/20 (30.0%) vs. 30/132 (22.7%) 1.46 ( ) Congestive hert filure, ischemic hert disese, vlvulr hert disese, stroke, peripherl rteril occlusive disese. Dt on smoking missing in 133 ptients (mong them 20 died).

7 Bloodstrem infection nd dietes mellitus 518 Bryn et l. [27] (2-fold), McFrlne et l. [28] (2.9-fold), nd Crton et l. [29] (1.7-fold). In our study cteremi with n unknown focus ws 2.3 times more common in dietics thn non-dietics, wheres the frequency of urosepsis ws similr in the two groups. This is in contrst to the study of Leiovici et l. [30], in which urosepsis ws 1.3 times more common in dietics thn in non-dietics, wheres the primry site of infection remined unknown in similr frction in oth groups. This difference my e explined y the fct tht the primry focus ws detected in >90% of episodes in our study, ut only in 70% of the episodes in the study y Leiovici et l. Crton et l. [29] reported frction of 14% of skin/soft tissue infection in cteremic dietic ptients. In our study only 2.9% of the dietic ptients hd skin infection s the primry focus, suggesting tht complicted dietic foot infection hs ecome less frequent. Comoridity ws the rule in dietic ptients. More thn 97% of the dietic ptients with cteremi hd t lest one underlying condition, chiefly hypertension (54.9%), neuropthy (25.4%), ischemic hert disese (25.4%), nd smoking (22.5%). Hypertension, peripherl rtery ostructive disese nd neuropthy were significntly more prevlent in dietic thn in non-dietic ptients. However, from our dt it cnnot e concluded tht these comoridities predispose for loodstrem infection, since control popultion of hospitlised dietic ptients without cteremi ws not nlysed. Interestingly, skin nd one infections were rre in our study, despite the lrge frction of ptients with neuropthy nd peripherl rtery ostructive disese. Foot cre, which hs gined incresing importnce in primry cre, thus seems to prevent loodstrem infection, given tht infection of the extremities ws n importnt primry source in older studies. E. coli nd S. ureus were the most common microorgnisms in oth groups of ptients. This is similr to studies of ptients with loodstrem infection in generl [31]. The only difference ws the 3.5-fold higher frequency of K. pneumonie cteremi in dietic s compred to non-dietic ptients. Similrly, in the study of Leiovici et l. [30], Klesiell ws lso overrepresented in dietics (13.5% vs.9.3%). In study deling with the epidemiology of cteremi due to Klesiell s compred to E. coli, dietes mellitus ws significnt risk fctor for the former microorgnism [32]. Similrly, mong 160 ptients with K. pneumonie liver scess, 75% of the ptients hd dietes compred to 4.5% of the ptients with polymicroil liver scess [33]. The reson for the high incidence of K. pneumonie in dietic ptients remins uncler. In the study mentioned ove, n impired Kupffer s cell function in dietic ptients my explin the incresed incidence of K. pneumonie, since this microorgnism seeds vi hemtogenous route wheres polymicroil scesses result from cholngitis. However, this hypothesis does not explin the entire difference, since Klesiell ws lso overrepresented in dietic ptients with urosepsis (25% vs. 8%) in the study y Leiovici et l. [30]. Hence incresed dhesion of Klesiell to epithelil cells of dietic ptients my e n dditionl fctor resulting in more Klesiell infection in this popultion. Incresed dhesion to epithelil cells of dietics hs een shown for two fimrited strins of E. coli, ut hs not yet een nlysed for Klesiell [34]. Both hypotheses remin to e tested. Secondry foci were lmost twice s frequent in dietic s in non-dietic ptients in our study. This finding indictes tht impired host defence fvours hemtogenous cteril seeding in dietic ptients. The deth rte due to cteremi per 1000 hospitl dmissions ws >5 times higher in dietic thn in non-dietic ptients. However, the mortlity rte ws similr in oth popultions. This indictes tht the susceptiility of dietics to loodstrem infection is incresed, ut the prognosis is similr once the infection is dignosed [35]. The difference etween the frequency of infections in dietic nd non-dietic ptients my e due to different helth-seeking ehviour. Dietic ptients hve frequent helthcre contcts, nd this my led to more common nd/or erlier dignosis of infections. However, this hypothesis my only explin the differences in uncomplicted infections [10]. As loodstrem infections re chiefly treted in n inptient setting, possile difference in incidence or outcome is due rther to different susceptiility or prognosis thn to different helthseeking ehviour. In non-dietic ptients, fctors ssocited with deth were similr to those in other studies on loodstrem infection [8, 35, 36]. Most fctors indicte severe infection (ICU sty, mechnicl ventiltion) or comoridity (dvnced ge, mlignncy). In dietic ptients two fctors remined significnt in the multivrite nlysis, ICU sty nd hyperglycemi. HA1c >7% ws not fctor significntly ssocited with deth. Hence hyperglycemi does not necessrily indicte poor seline dietes ut could lso e the result of severe sepsis. Poor glucose control hs een demonstrted s risk fctor in criticlly ill ptients regrdless of whether they were dietics or not [37]. The min limittion of our study is its retrospective design. However, thnks to our electronic ptient chrt nd lortory system, the qulity of the dt cn e regrded s relile. Only 10 screened ptients hd to e excluded ecuse of missing clinicl documenttion. Our study hs two min clinicl implictions. First, in dietic ptients with sepsis, empiric ntiiotic therpy should include efficcy ginst K. pneumonie. Further, secondry foci should e ctively sought in order to void filure due to lck of dringe nd/or of prolonged ntimicroil therpy.

8 SWISS MED WKLY 2008;138(35 36): In conclusion, dietics re t incresed risk of loodstrem infection ut hve similr mortlity. The incresed risk of complictions mens significntly prolonged hospitl sty. Correspondence: Werner Zimmerli, MD Medizinische Universitätsklinik Rheinstrsse 26 CH-4410 Liestl Switzerlnd E-Mil: werner.zimmerli@unis.ch References 1 Joshi N, Cputo GM, Weitekmp MR, Krchmer AW. Infections in ptients with dietes mellitus. N Engl J Med. 1999; 341: Bertoni AG, Sydh S, Brncti FL. Dietes nd the risk of infection-relted mortlity in the U.S. Dietes Cre. 2001;24: Cooper G, Pltt R. Stphylococcus ureus cteremi in dietic ptients. Endocrditis nd mortlity. Am J Med. 1982;73: Hill PC, Birch M, Chmers S, Drinkovic D, Ellis-Pegler RB, Everts R, et l. Prospective study of 424 cses of Stphylococcus ureus cteremi: determintion of fctors ffecting incidence nd mortlity. Intern Med J. 2001;31: Fctor SH, Levine OS, Schwrtz B, Hrrison LH, Frley MM, McGeer A, Schucht A. Invsive group A streptococcl disese: risk fctors for dults. Emerg Infect Dis. 2003;9: Jckson LA, Hilsdon R, Frley MM, Hrrison LH, Reingold AL, Plikytis BD, et l. Risk fctors for group B streptococcl disese in dults. Ann Intern Med. 1995;123: Nuorti JP, Butler JC, Frley MM, Hrrison LH, McGeer A, Kolczk MS, Breimn RF. Cigrette smoking nd invsive pneumococcl disese. Active Bcteril Core Surveillnce Tem. N Engl J Med. 2000;342: Trmpuz A, Widmer AF, Fluckiger U, Henggi M, Frei R, Zimmerli W. Chnges in the epidemiology of pneumococcl cteremi in Swiss University Hospitl during 15-yerperiod, Myo Clin Proc. 2004;79: Kech C, Elzi L, Sendi P, Frei R, Lifer G, Bssetti S, Fluckiger U. Course nd outcome of Stphylococcus ureus cteremi: retrospective nlysis of 308 episodes in Swiss tertiry-cre centre. Clin Microiol Infect. 2006;12: Muller LM, Gorter KJ, Hk E, Goudzwrd WL, Schellevis FG, Hoepelmn AI, Rutten GE. Incresed risk of common infections in ptients with type 1 nd type 2 dietes mellitus. Clin Infect Dis. 2005;41: Clvet HM, Yoshikw TT. Infections in dietes. Infect Dis Clin North Am. 2001;15: Geerlings SE, Hoepelmn AI. Immune dysfunction in ptients with dietes mellitus (DM). FEMS Immunol Med Microiol. 1999;26: Vlerius NH, Eff C, Hnsen NE, Krle H, Nerup J, Soeerg B, Sorensen SF. Neutrophil nd lymphocyte function in ptients with dietes mellitus. Act Med Scnd. 1982;211: Al-Loureiro TC, Munhoz CD, Mrtins JO, Cerchiro GA, Scvone C, Curi R, Snnomiy P. Neutrophil function nd metolism in individuls with dietes mellitus. Brz J Med Biol Res. 2007;40: Ryfield EJ, Ault MJ, Keusch GT, Brothers MJ, Nechemis C, Smith H. Infection nd dietes: the cse for glucose control. Am J Med. 1982;72: Moutschen MP, Scheen AJ, Lefevre PJ. Impired immune responses in dietes mellitus: nlysis of the fctors nd mechnisms involved. Relevnce to the incresed susceptiility of dietic ptients to specific infections. Diete Met. 1992;18: McMhon MM, Bistrin BR. Host defenses nd susceptiility to infection in ptients with dietes mellitus. Infect Dis Clin North Am. 1995;9: Lipsky BA, Pecorro RE, Chen MS, Koepsell TD. Fctors ffecting stphylococcl coloniztion mong NIDDM outptients. Dietes Cre. 1987;10: von Eiff C, Becker K, Mchk K, Stmmer H, Peters G. Nsl crrige s source of Stphylococcus ureus cteremi. Study Group. N Engl J Med. 2001;344: Chi CY, Wong WW, Fung CP, Yu KW, Liu CY. Epidemiology of community-cquired Stphylococcus ureus cteremi. J Microiol Immunol Infect. 2004;37: Thomsen RW, Hundorg HH, Lervng HH, Johnsen SP, Schonheyder HC, Sorensen HT. Dietes mellitus s risk nd prognostic fctor for community-cquired cteremi due to enterocteri: 10-yer, popultion-sed study mong dults. Clin Infect Dis. 2005;40: Thomsen RW, Jepsen P, Sorensen HT. Dietes mellitus nd pyogenic liver scess: risk nd prognosis. Clin Infect Dis. 2007;44: Chen SC, Lee YT, Li KC, Cheng KS, Jeng LB, Wu WY, et l. Risk fctors for developing metsttic infection from pyogenic liver scesses. Swiss Med Wkly. 2006;136: Horvth K, Jeitler K, Berghold A, Erhim SH, Grtzer TW, Plnk J, et l. Long-cting insulin nlogues versus NPH insulin (humn isophne insulin) for type 2 dietes mellitus. Cochrne Dtse Syst Rev. 2007:CD Krentz AJ, Biley CJ. Orl ntidietic gents: current role in type 2 dietes mellitus. Drugs. 2005;65: Hoogwerf BJ. Postopertive mngement of the dietic ptient. Med Clin North Am. 2001;85: Bryn CS, Reynolds KL, Metzger WT. Bcteremi in dietic ptients: comprison of incidence nd mortlity with nondietic ptients. Dietes Cre. 1985;8: McFrlne IA, Brown RM, Smyth RW, Burdon DW, FitzGerld MG. Bcteremi in dietics. J Infect. 1986;12: Crton JA, Mrdon JA, Nuno FJ, Fernndez-Alvrez R, Perez-Gonzlez F, Asensi V. Dietes mellitus nd cteremi: comprtive study etween dietic nd non-dietic ptients. Eur J Med. 1992;1: Leiovici L, Smr Z, Koniserger H, Klter-Leiovici O, Pitlik SD, Drucker M. Bcteremi in dult dietic ptients. Dietes Cre. 1991;14: Lffer RR, Frei R, Widmer AF. Epidemiology of septicemis in university hospitl over 5 yers. Schweiz Med Wochenschr. 2000;130: Hnsen DS, Gottschu A, Kolmos HJ. Epidemiology of Klesiell cteremi: cse control study using Escherichi coli cteremi s control. J Hosp Infect. 1998;38: Wng JH, Liu YC, Lee SS, Yen MY, Chen YS, Wng JH, et l. Primry liver scess due to Klesiell pneumonie in Tiwn. Clin Infect Dis. 1998;26: Geerlings SE, Meilnd R, vn Lith EC, Brouwer EC, Gstr W, Hoepelmn AI. Adherence of type 1-fimrited Escherichi coli to uroepithelil cells: more in dietic women thn in control sujects. Dietes Cre. 2002;25: Weinstein MP, Towns ML, Qurtey SM, Mirrett S, Reimer LG, Prmigini G, Reller LB. The clinicl significnce of positive lood cultures in the 1990s: prospective comprehensive evlution of the microiology, epidemiology, nd outcome of cteremi nd fungemi in dults. Clin Infect Dis. 1997;24: Uzun O, Aklin HE, Hyrn M, Unl S. 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