Intensve Care Med (1992) 18:398-404 Intensve Care Medcne 9 Sprffger-Verlag 1992 Org&als Preventon of nosocomal nfecton n crtcally ll patents by selectve decontamnaton of the dgestve tract A randomzed, double blnd, placebo-controlled study L.A. Rocha I, M.J. Martln 1, S. Pta ~, J. Paz ~, C. Seco 2, L. Margusno 2, R. Vllanueva 3 and M.T. Durfn 3 Departments of l Intensve Care Unt, 2pharmacy, and 3Mcrobology, Juan Canalejo Hosptal, La Corufa, Span Receved: 31 December 1991; accepted: 13 July 1992 Abstract. Objectve: To evaluate the effect of a method of Selectve Decontamnaton of the Dgestve Tract (SDD) on colonzaton, nosocomal nfecton (NI), bacteral resstance, mortalty and economc costs. Desgn: Randomzed, double blnd, placebo controlled study. Settng: Polyvalent ntensve care unt (ICU) of a tertary care hosptal wth 27 beds. Patents: 101 patents wth > 3 days of mechancal ventlaton and > 5 days of stay, wthout nfecton at the start of the study. 47 belonged to the Treated Group (TG) and 54 to the Placebo Group (PG). Interventons: The TG was gven Cefotaxme.v. (6 g/day) for the frst four days and an assocaton of Polymyxn E, Tobramycn and Amphothercn B at the oropharyngeal and gastrontestnal level throughout the whole stay. Results: In the TG, colonzaton by gram-negatve agents at oropharyngeal, tracheal and gastrontestnal level fell sgnfcantly. There was a sgnfcant drop n the overall, respratory and urnary NI (26 070 vs 63 070, p < 0.001; 15 07o vs 46070, p < 0.001; 907o vs 31070, p < 0.01). The overall mortalty and NI related mortalty was less n the TG (21070 vs 44070, ; 207o vs 20070, p<0.01). The economc costs, mechancal ventlaton tme and length of stay were smlar. The percentage of bacteral solatons resstant to Cefotaxme and Tobramycn was greater n the TG (38070 vs 15070 and 3807o vs 907o, p<0.001). Conclusons: colonzaton by gram-negatve bacll, NI and the mortalty related to t can be modfed by SDD. Contnuous bacterologcal survellance s necessary. Key words: Selectve decontamnaton of the dgestve tract - Infecton preventon - Nosocomal - Intensve care unt - Artfcal ventlaton Nosocomal nfecton (NI) contnues to be a major medcal problem n ICUs where, due to the severty of the llness, the poor defences and the handlng of patents [1, 2], ts ncdence stands at 23070-28070, n some cases exceedng 80% [3-5]. Even wth careful hygenc measures and a restrctve antbotc polcy ts rate s hgh [6-8]. Mortalty, length of stay and other hosptal costs can be altered by the development of a NI [8-12]. Some 70~ are of endogenous orgn, caused by organsms that had prevously colonzed the patent, especally at the oropharyngeal and gastrontestnal level [3, 13-17]. Dgestve decontamnaton wth non-absorbable antbotcs s an old technque for preventng NI, used bascally n hematologcal neoplasas wth varyng results [18]. In 1984 Stoutenbeek et al. [5] publshed the results of the use n ICU patents of a method of Selectve Decontamnaton of the Dgestve Tract (SDD) whose spectrum amed to respect the habtual anaerobc mcroflora partcpatng n resstance to colonzaton [19]; they cut down the rate of NI from 81% to 16070. Other authors later confrmed the use of SDD n ICUs [20-29], though mportant ponts reman unclarfed [29-33] (knds of patents beneftng, development of resstance, effect on hosptal mortalty and stay). We therefore began a prospectve, randomzed, double blnd, placebo controlled study wth the am of evaluatng ts effcency n the preventon of NI n ICUs and the nfluence on colonzaton and the other aforementoned varables. Materal and methods Study desgn We ncluded only those patents wth mechancal ventlaton (MV)> 3 days and stay n ICU>5 days. Causes for excluson were: nfecton or strong suspcon of ths at the start of the MV, antbotc treatment n the prevous seven days, neutropena (< 500 pmn/ml) and fever, pregnancy, and a hstory of hypersenstvty to the agents used n SDD. Those patents that we expected to meet the crtera for ncluson were ntally assged n the center's Pharmacy Servce to the placebo group (PG) or the treated group (TG), accordng to a table of random dstrbuton numbers generated by computer. The necessary medcaton was sent dally n all ndvdualzed manner. All were carrers of a nasogastrc tube, a bladder catheter connected to a closed dranage system and central venous catheters. We conducted stress ulcer prophylaxs solely wth antacds and H2 blockers. The ventlator tubngs were changed every 48 h. Every day, patents underwent physcal examnaton and chest radograph for sgns of nfecton, and bochemcal and hematologcal data were gathered. Problems related to the nfectons
399 were dscussed n clncal sessons. If these were lfe threatenng they were treated ntally wth an assocaton of cephthazdm or pperacln and tobramycn, usng metrondazole or clndamycn f anaerobcs were suspected; later we used the antbotcs that were ndcated. We only used cefotaxme n SDD or n nfectons wth bacterologcal documentaton that made ths necessary. The severty of ther llness was tabulated by APACHE II [341, the Glasgow coma score (GCS) and number of organ-system falures [351. Decontamnaton regmen The TG was gven cefotaxme.v. (6 g/day) for the frst four days; throughout the whole stay n the unt a paste of carboxymethylcellulose (0.5 g/q..d.) wth 2% of polymyxn E, tobramycn and amphothercn B was appled to the oropharynx, and a soluton contanng 100 mg of polymyxn E, 80 mg of tobramycn and 500 mg of amphothercn B was gven va a nasogastrc tube four tmes a day. The PG was gven the same quantty of paste/solutons contanng just an nert colorant substance. Bacterologcal survellance Randomly and up to a maxmum of four patents smultaneously, n the 24 h followng ther ncluson and then twce a week samples of oropharynx, tracheal asprate, gastrc asprate, and feces were cultured. When there was a suspcon of nfecton all the necessary bacterologcal samples were taken. They were cultured aerobcally usng standard mcrobologcal technques and anaerobcally when there was a clncal ndcaton. Senstvty to cefotaxme and tobramycn was studed by means of dsk dffuson technques. The survellance samples were taken by Dr MJ Martn wthout any of the other nvestgators or doctors n charge havng access to them. Defntons () Lower respratory tract nfecton: Presence of purulent pulmonary secretons, new nfltrates n tl~e chest X-rays and one of the followng fndngs: fever/hypotherma, leukocytoss/leukopena, postve physcal examnaton and drop n arteral partal oxygen pressure. Non-essental bacterologcal dagnoss was carred out by means of dentfcaton of the agent n two postve samples of tracheal asprate, assocated blood culture, pleural lqud or, n the latest patents, n protected bronchal brushng. () Urnary tract nfecton: Urne culture wth > 100000 cfu/ml and > 3 leukocytes/hgh-power feld. O) Wound nfecton: Data on nflammaton and purulent secreton from the wounds, wth postve culture. (v) Bacterema-sepss: Postve blood culture assocated wth fever, leukocytoss and/or hypotenson. Coagulase-negatve Staphylococcus had to be confrmed n two dfferent extractons. (v) Catheter-assocatedseptcema: Isolaton of the same agent n blood culture and semquanttatve culture of the ntravascular segment wthout other sources of nfecton. (v) Supernfecton: That developed durng antbotc treatment, caused by germs resstant to t. (v) Colonzaton: Presence of a potentally pathogenc agent n an organ or system wthout sgns of nfecton durng more than three days (solated n at least two consecutve samples). (vff) Extus assocated wth nfecton: That occurrng as part of an nfecton that causes shock and severe respratory falure (PaO2/ FO 2 < 150). (x) NI ndex: percentage of nfected patents. (x) NI rate: Number of nfectons developed among all the patents, expressed as a percentage. Statstcal analyss The Fsher's exact test was used to compare categores. The averages were compared by means of the Student's t-test. Survval was estmated wth the Kaplan-Meer method compared wth the log-rank test and adjusted accordng to the Cox semparametrc model. A value of p < 0.05 was consdered sgnfcant. Results Durng the 14 months of the study, 1600 patents entered the unt. Intally, 151 receved medcaton (SDD or placebo), but only 101 met the requrements demanded. The remander were excluded because of: development of nfecton n the frst 48 h [4], extubaton before the thrd day [15], dscharge before the ffth day [31]. Ffty-four belonged to the PG and 47 to the TG. They were comparable n terms of age, sex and scorng on llness severty scales. The dagnostc groupng was smlar, wth traumatc patents domnatng both groups, head trauma beng the most frequent. Wthn medcal patents complcated schemc cardopathy and acute cerebrovascular accdent n young people predomnated (Table 1). Colonzaton The percentage of colonzed patents n each group at the oropharyngeal, tracheal, gastrc and rectal level followed a smlar profle (Fg. 1). Whle colonzaton by Gramnegatve agents n the TG stayed steady or dropped compared wth the frst sample, except n the trachea, n the PG t progressvely rose, becomng sgnfcant from the fourth day on. At the rectal level, the dfferentaton was slower, becomng sgnfcant from day 13. In the PG the Table 1. Patent dstrbuton and dagnostcs Placebo group Treated group (n = 54) (n = 47) Age 44.1 (SD: 21) 42.8 (SD: 19)* (range) (16-62) ('15-79) Male/female 47/7 38/9 * APACHE II score 16 (SD: 5) 14.9 (SD: 5)* (range) (7-31) (7-27) Glasgow coma score (GCS) 9.1 (SD: 3) 9 (SD: 3.5)* (range) (5-15) (5-15) No. of patents wth GCS<8 19 (35%) 22 (470/0)* Organ-system falure (OSF) 1 organ 20 (37%) 18 (38%)* 2 organs 11 (20%) 14 (30%)* 3 organs 0 1 (2%) Medcal 12 (22%) 9 (19%)* Cardac dsease 5 4 Neurologc dsease 7 5 Traumatc 42 (78%) 38 (81%)* Thoracc trauma 2 2 Spnal cord njury 3 4 Head trauma and assocated 37 32 * Not sgnfcant; OSF, number of patents wth organ-system falure
400 100 - ~ m. --m-- 9 Q [3 80 _ --, 6o._,u ~ x p < 0.05 9 "~ / + p <0.01 o_ / 40 / o p <0.001 // # / 20 -a # o o o- o o o o... o ~ ~ o ~ 01 --,o..., Day: 1 4 7 I'0 13 ' 16 ' 19 n: 30/34 30/34 27/25 23/19 17/14 12/13 9/12 o TreatedG.(G-) u PlaceboG.(G-) 9 Placebo G. (G+) 9 Treated G. (G+) Fg. 1. Oropharyngeal colonzaton. Evoluton of the percentage of patents colonzed by Gram-postves (G+) and Gram-negatves (G-) n each group, n: Number of patents sampled n each group (TG/PG) presence of Gram-postve organsms gradually dropped, but n the TG t remaned the same or ncreased, becomng sgnfcant startng from days 7-10. After days 4-7 Staphylococcus, manly S. aureus, and Enterococcus predomnated n both groups, wth a hgher percentage n the TG. Oropharynx: In the frst sample 20% of PG patents showed Gram-negatve organsms and 7% of the TG (). After the fourth day (54% vs 3%, p < 0.001)> 80% and <8~ respectvely, dd so. The ntal solaton of Gram-postve agents was 94% and 97% (); from day 7 (84% vs 100%, p < 0.05) ths was < 80% n the PG and 100% n the TG. Tracheal asprate: Gram-negatve bactera colonzed 35 % n the PG and 6% n the TG (p< 0.01) on day one. From the tenth day (92% vs 32%, p<0.001) colonzaton occurred n more than 90% of the PG and between 30%-40% n the TG. Gram-postves were ntally solated n 70% and 75~ of patents (); n the PG they dropped, stayng steady from day ten (35% vs 91%, p<0.001) at around 30% and n the TG they contnued at above 85%. Gastrc asprate: The presence of Gram-negatves started at 31~ and 6~ (p< 0.05). In the PG they rose, from day seven (61~ vs 3~ p < 0.001) remanng at around 60~ and n the TG they contnued below 6~ After day one (2307o vs 6%, ) Gram-postve agents stayed below 34o7o n the PG and n the TG rose to 69~ on day 16 (8~ vs 69o70, p<0.01). Feces: From 11% n the PG and 3% n the TG (), Gram-negatve bactera (no E. col) rose up to day 16 (58% vs 7%, p < 0.01) n the frst group, whle n the second they fell startng from day ten (39% vs 19%, ). Colonzaton by Eschercha col (89070 vs 91070, on day one) contnued above 70% n the PG, and n the TG, after the seventh day (75% vs 37~ p<0.01), was less than 14%. Infectons The NI ndex fell from 63% (34/54) n the PG to 26% (12/47) n the TG Go<0.001). 49% (28/57) of NIs n the PG, and 13% (2/15) n the TG (), were early (< 5 days). Respratory nfecton (Table 2): 46% of patents n the PG and 15~ of the TG had pneumona 6o< 0.001). Ths Table 2. Summary of organsms causng nfecton Placebo group Treated group Respratory nfecton, 25/54 (46%) 7/47 (15%)p<0.001 Staphylococcus aureus 15 5 Streptococcus pneumonae 2 0 Enterococcus 0 1 Haemophlus nfluenzae 9 0 Pseudomonas spp. 4 + 4 1 Acnetobacter spp. 4 + 8 1 Klebsella spp. 1 0 Proteus spp. 1 + 1 0 Pasteurella spp. 1 0 Aeromonas spp. 0 + 1 0 Urnary tract nfecton 17/54 (31%) 4/47 (9%) p<0.01 Staphylococcus aureus 1 1 Coagulase-negatve 2 0 staphylococcus En terococcus 5 1 Eschercha col 4 + 1 1 Klebsella spp. 4 0 Enterobacter spp. 3 0 Proteus spp. 2 0 Pseudomonas spp. 0 1 + 1 Acnetobacter spp. 0 1 Bacterema 10/54 (19070) 3/47 (607o) N.S. Catheter-assocated (epsodes: 3) (epsodes: 3) Staphylococcus aureus 0 2 Coagulase-negatve 2 1 staphylococcus Klebsella spp. 1 0 Pulmonary source (epsodes: 5) Staphylococcus aureus 1 0 Streptococcus pneumonae 1 0 Acnetobacter spp. 2 0 Pseudomonas spp. 1 0 Urnary source (epsodes: 2) Staphylococcus aureus 1 0 Klebsella spp. 1 0 Other sources (epsodes: 3) Staphylococcus aureus 1 0 A cnetobacter spp. 1 0 Proteus spp. 1 0 Wound nfecton 1/54 (2070) 2/47 (4%) N.S. Staphylococcus aureus 1 1 Enterococcus 0 1 Eschercha col 0 1 Pseudomonas spp. 0 1 Bacterocles spp. 1 0 Overall Gram-postve agents 32/88 (36%) 13/21 (62%) Overall Gram-negatve agents 56/88 (64%) 8/21 (38070), not sgnfcant; n/n, ndex of each nfecton type; the rate of bacteremas drops from 24070 (13/54) to 6% (3/37), p<0.001; +n, number of agents solated n respratory supernfectons and urnary renfectons
401 started at 4.8 days (SD: 2.8) n the PG and at 16.8 days (SD: 22) n the TG, wth 72% and 14% respectvely (p <0.05) beng early. The etology was Gram-postve, manly Staphylococcus aureus, n 68% of epsodes n the PG and n 71% n the TG. Apart from Haemophlus nfluenzae n the PG, Pseudomonas and Acnetobacter were the most frequent Gram-negatves. In the TG 86~ were cured and n the PG 64% were cured or ntally mproved snce 32% (9/25) showed supernfecton caused exclusvely by Gram-negatve agents. The TG had no supernfectons. Urnary nfecton (Table 2): 31% of ndvduals n the PG showed ths, and 9% n the TG (p<0.01). In the frst group ths started at 9.8 days (SD: 13) and n the second at 13.2 days (SD: 8.5), 35% and 25% () beng early. 47% of cases n the PG and 50% n the TG were caused by Gram-postves. 82~ and 100%, respectvely, were cured. In both groups there was one renfecton. Bacterema (Table 2): The ndex fell from 19% n the PG to 6% n the TG () and the rate went from 24~ (13/54) to 6~ (3/47) (p<0.001). It appeared sooner n the PG (6.2 days; SD: 3) than n the TG (10.6 days; SD: 3), beng early n 31~ and 0% of epsodes n each group. The focus was exclusvely the vascular catheter n the TG, and n the PG the lung was the man source [5]. In the TG we only dentfed Staphylococcus. In 46% of bacteremas n the PG we solated Gram-postve bactera. Wound nfecton (Table 2): One patent (2%) n the PG showed ths and two (4%) n the TG. Both nfectons were late. One ndvdual n the TG was not cured. Resstances In the PG 15O7o (144/964) of bacteral solatons were resstant to cefotaxme and 38% (175/462) n the TG (p<0.001). Resstance to tobramycn was 9070 and 38%, respectvely (p<0.001). The percentage of resstances to cefotaxme and tobramycn n each of the organsms was usually greater n the TG. Sgnfcance was reached n Staphylococcus aureus wth p<0.001 (cefotaxme: 14O7o (19/136) n the PG and 52~ (144/277) n the TG; tobramycn: 10o7o (13/136) n the PG and 52~ (144/277) n the TG) and n Acnetobacter wth for tobramycn (330/0 (47/143) n the PG and 61o70 (14/23) n the TG). The resstance patterns of agents responsble for nfectons were smlar n both groups (Table 3). Mortalty Durng the study the general mortalty n our unt was 20.5~ Overall mortalty n the PG was 44~ (24/54) and 21~ (10/47) n the TG (). Mortalty due to the underlyng dsease was 24~ and 19~ (), respectvely; that related to NI was 20o/o (11/54) n the PG and 2O/o (1/47) n the TG (p<0.01). A dfference exsted on comparng the survval curves (Fg. 2) by means of the logrank test (p < 0.05). After adjustng wth those varables that could have nfluenced survval at the begnnng (age, APACHE II, GCS and presence of organ-system falure) the rsk of death was 2.3 tmes hgher n the PG (Cox model: 95O/o confdence nterval, 1.08 to 4.98; ). Costs We used therapeutc antbotcs (TA) n 56% of patents n the PG and n 34% n the TG (). The cost of TA/patent/day was 2736 pesetas n the PG and 1334 pesetas n the TG (). The cost of SDD/patent/day was 2785 pesetas. The overall cost of antbot- Table 3. Resstance patterns of organsms solated from nfected patents Ce~t~me Tobramycn Placebo Treated Placebo Treated Staphylococcus aureus 4/20 (2007o)* 4/9 (44%) 4/20 (20%)* 4/9 (44%) Coagulase-negatve staphylococcus 2/4 (50%)* 1/1 (100070) 2/4 (50%)* 1/1 (100%) Streptococcus pneumonae 0/3 0 nd/3 0 Enterococcus 5/5 (100%)* 3/3 (100%) 5/5 (100%)* 3/3 (100%) Haemophlus nfluenzae 0/9 0 nd/9 0 Eschercha col 0/4 0/2 0/4 0/2 Proteus spp, 0/5 0 0/5 0 Klebsella spp. 0/7 0 0/7 0 Enterobacter spp. 1/3 (33%) 0 0/3 0 Pasteurella spp. 0/1 0 0/1 0 Aeromonas spp. 0/1 0 /1 0 Acnetobacterspp. 8/15 (5307o)* 1/2 (50%) 6/15 (4007o)* 1/2 (50070) Pseudomonasspp. 7/9 (78%)* 2/3 (67%) 4/9 (44%)* 1/3 (330/o) Bacterodes spp. nd/1 0 nd/1 0 Overall Grarn-postveagents 11/32 (34%)* 8/13 (62%) 11/29 (38%)* 8/13 (620/o) Overall Gram-negatve agents 16/54 (30~ 3/7 (43%) 11/45 (24o7o)* 2/7 (29%) * Not sgnfcant; nd, not done
402 1.0 0,9 0.8 0,7 0,6 0.5 0.4 0.3 0.2 0.1 0 PR 1 L, "1 I I-- l I L.......... I I I I I I I I I 20 40 60 80 I00 120 140 160 180 200 Days Fg. 2. Survval n both groups s sgnfcantly dfferent (log-rank test, p < 0.05). Adjustng wth varables that on arrval could modfy survval, the rsk of death was 2.3 tmes hgher n the PG (Cox model, p < 0.05). Treated G: ; Placebo G:... cs/patent/day was 2736 n the PG and 4045 pesetas n the TG (p < 0.05). There was no dfference n other antbotc costs (Table 4). The average tme of MV was 13 days n both groups. In non-nfected survvors the tme was 7.7 days (SD: 5) n the PG and 11.8 days (SD: 9) n the TG (), (Table 4). The average stay n the PG was 17.8 days (SD: 15) and 18.8 days (SD: 20) n the TG (). In non-nfected survvors ths was 11 days (SD: 5) and 17 days (SD: 10), respectvely (p< 0.05). The cost of stay/patent was smlar n both groups. The cost/survvor was 3477246 pesetas n the PG and 2582980 pesetas n the TG (Table 4). Dscusson The frst studes on SDD used a hstorc control group [5] or a consecutve control and treatment group n order to prevent the use of the two dfferent antbotc regmens nterferng wth the colonzaton/nfecton profles of the ndvduals [23]. Later randomzed studes demonstrated the possblty of carryng out smultaneous desgns that would ensure that the patents were handled equally [22, 32]. We selected patents subjected to MV and wth a stay n ICU of >5 days n order to consttute a hgh rsk group for developng NI and one whch could beneft most from SDD [3, 5, 8, 23]. In order to prevent nterferences n the results we excluded prevously nfected patents, the use of sucralfate and we conducted a double blnd, placebo controlled study [3, 5, 19, 20, 27]. As wth other groups [ 5, 20-28, 31, 32], we found a sgnfcant reducton n colonzaton by Gram-negatve bactera at all levels. Ths occurred early (days 4-7) except at the rectal level (days 7-13), probably due to ntestnal paress that these patents can show [5]. Unlke n the PG, n the TG the presence of Gram-postve agents, bascally Staphylococcus and Enterococcus after day 4, remaned steady and even ncreased. These germs can be regarded as formng part of the usual flora [36, 37] and perhaps because of ths they are not normally descrbed, though other groups also observed ths fact [24]. The dfference n the percentage of patents n each group colonzed at the begnnng was due to the fact that the sample was not always taken pror to admnsterng SDD and the germs solated n the PG (Haemophlus, E. col, Klebsella, Enterobacter) are nhbted by t. Related to the changes produced n the colonzaton profles, a sgnfcant drop n the NI ndex (63070 vs 26070) was acheved, wth a marked reducton n Gram-negatve agents as beng responsble for ths. As wth the majorty of SDD works [28, 31, 32] ths was related to a drop n respratory nfecton; but as wth other authors we also found a fall n urnary nfectons [3, 25, 28] and n bacteremas [3], though, unlke the Utrecht and The Hague groups [22, 25], catheter related nfectons, caused exclusvely by Staphylococcus n the TG, dd not fall. As wth Gastnne et al. [29], we only observed respratory supernfectons n the PG, caused solely by Gram-negatve organsms. Though some authors [21, 26, 27, 40] reduced NIs wthout parenteral prophylaxs, n our study t probably played a major role due to the hgh percentage of early nfectons, manly at the respratory level. The rsk of a mult-resstant bacteral stran appearng durng the use of an antbotc prophylaxs always exsts. But so far no clncally mportant resstances have been found [31, 32], even n prolonged follow-ups [38, 39]. Though, as wth the Unversty of Ulm group [24], we dd record a rse n resstances n the bacteral populaton of the TG, ths had no clncal relevance snce not only dd the resstance patterns of the agents responsble for nfectons not dffer, NIs also decreased and ther curng percentage was greater n the TG, wth a lower mortalty. Nevertheless, ths, along wth the selecton of a Grampostve flora potentally responsble for serous nfectons, means that the need must be emphaszed for longterm survellance. The relaton between the development of NI and the rse n mortalty s well known but s not easy to demonstrate snce a patent may de wth an nfecton before ths becomes the cause [9]. The reducton n the ncdence of NI wth SDD dd not cause a unform drop n mortalty [31-33], though some found a decrease n selected groups of patents [23, 40] or n the mortalty assocated wth nfecton [22]. Not even n an extensve double blnd study wth a greater number of medcal patents was an mprovement n survval acheved [29]. Only one randomzed study [25] observed, as dd we, a drop n the overall mortalty wth a smultaneous decrease n that assocated wth NI. Ths s probably due to our populaton beng manly traumatc, wth mdrange APACHE II score and prolonged stay, somethng that has already been ponted out by Ledngham et al. [23], as well as wth a non-termnal stuaton on admsson, as Gross et al. establshed [9].
403 Table 4. Costs Placebo group Treated group (n = 54) (n = 47) Antbotcs Therapeutcal antbotcs (TA) Number of patents 30 (56%) Days/patent 8 (SD: 10) Days/nfected patent 14.4 (SD: 9) No. of TA/patent 1.7 (SD: 1.9) No, of TA/nfected patent 3 (SD: 1.5) Overall cost 3 589 803 Cost/patent 66478 Cost/nfected patent 119660 Cost/patent/day 2736 Cost/nfected patent/day of therapy 7 804 SDD Overall cost 0 Cost of parenteral SDD 0 Cost of topcal SDD 0 Cost/patent 0 Cost/patent/day 0 All the antbotcs Overall cost 3 589 803 Cost/patent 66478 Cost/patent/day 2 736 Cost/day 3716 Length of artfcal ventlaton Days/patent 13.2 (SD: 9) Days/survvor 15.2 (SD: 11) Days/nfected survvor 19 (SD: 11) Days/non-nfected survvor 7.7 (SD: 5) Length of stay Days/patent 1%8 (SD: 15) Days/survvor 23.5 (SD: 17) Days/nfected survvor 29.8 (SD: 18) Days/non-nfected survvor 11 (SD: 5) Cost of stay/patent 1931803 Cost of stay/survvor 3477246 16 (34%) 4.9 (SD: 14,4 (SD: 0.8 (SD: 2.3 (SD: 1733 241 36 878 108 328 1334 6966 1846178 763 656 1082 522 39280 2785 3579419 76157 4045 4045 lo) 13) 1.5) 1.8) 13.1 (SD: 15) 14.5 (SD: 17) 22 (SD: 28) 11.8 (SD: 9) 18.8 (SD: 20) 21.7 (SD: 21) 33.4 (SD: 37) 17 (SD: 10) 2033410 2582980 Costs are expressed n pesetas (1 US$ = 107.11 pesetas). The average cost/bed/day n our ICU s 107989 pesetas As wth other studes [22, 23], the use of therapeutc antbotcs decreased wth a sgnfcantly lower cost/patent/day n the TG. Ths savng was canceled out by the hgher prce represented by SDD, whch meant that the average cost of the total antbotcs/patent/day was greater n the TG, though the fnal cost was smlar n both groups. We dd not observe the possblty of rasng the cost of the treatment of nfectons n the TG due to the appearance of resstant organsms [12] snce the cost/nfected patent was not dfferent. Unlke other authors [5, 20-22, 40], who noted a reducton n the stay of TG patents, we, as wth Ulrch et al. [25], dd not fnd any dfferences n the MV tme nor n the stay of both groups. Ths s probably related to the decrease n the mortalty and the appearance later on of nfectons n the TG. Ths delay, whch has already been noted prevously [40], along wth a more prolonged MV and stay tme among survvors n the TG, allows us to speak of havng acheved a greater "nfecton-free nterval" n ths group. Fnally, t must be ponted out from the cost-effectveness vewpont that the overall prce/survvor was less n the TG. To summarze, n selected patents n an ICU, SDD can modfy colonzaton by Gram-negatve bacll, the ncdence of NI and assocated mortalty wthout ncreasng costs. Durng the study perod, no resstance of clncal mportance has been noted. Acknowledgements. We would lke to thank Dr. P. Llnares and Dr. J. Garau for ther amable collaboraton n the preparaton of ths manuscrpt. We would also lke to thank all the personnel of the partcpatng servces for ther nvaluable support. References 1. Zmmerl W (1985) Impared host defence mechansms n ntensve care unt patents. Intensve Care Med 11:174-178 2. Hoyt DB, Ozkan AN (1991) Immunosuppresson n trauma patents. J Intensve Care Med 6:71-90 3. Stoutenbeek CP, van Saene HKF, Zandstra DF (1988) Effect of selectve decontamnaton on colonzaton and nfecton rate n nten-
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