New Clinical Data on the Prophylaxis of Infections in Abdominal, Gynecologic, and Urologic Surgery Adolfo Turano, MD, and Multicenter Study Group, Brescia,Italy
Two dose schedules of the antibiotic cefotaxime were c o m p a r e d in a prospective, randomized 2 2 6 center study of 3 , 6 7 0 patients undergoing abdominal, gynecologic, and urologic surgery. Schedule A c o n s i s t e d of a single p r e o p e r a t i v e dose and schedule B consisted of one p r e o p e r a t i v e dose followed by two p o s t o p e r a t i v e doses. T h e r e was no significant difference in the frequency of wound infection or bacteriuria b e t w e e n the two schedules. Schedule B was associated with a significantly higher i n c i d e n c e of postoperative pyrexia, further antibiotic therapy, l o c a l side effects, and e x t e n d e d hospital stay. O n e dose p r o b a b l y has less i m p a c t on the intestinal flora. T h e r e f o r e , single-dose cefotaxime is as effective and less costly when c o m p a r e d with multiple-dose cefotaxime for c o m m o n surgical p r o c e d u r e s lasting less than 3 hours.
From the Istituto di Microbiologia, Universit~t degli Studi di Brescia, Spedali Civili, Piazza Spedali Civili, Brescia, Italy. Requests for reprints should be addressed to Professor Adolfo Turano, Istituto di Microbiologia,Universit~tdegli Studi di Brescia, Spedali Civili, Piazza Spedali Civili, 1, 25100 Brescia, Italy. 16S
he prophylactic use of antibiotics for surgical proce-
T dures has become a standard practice. Surgeons throughout the world recognize the advantages, in virtually all types of procedures, of having a microbiologically active drug available during the critical interval in which bacterial contamination can occur. To achieve this aim, a great variety of antibiotics are currently administered before or during the operation and, if necessary, for some days after the closure of the wound. Cefotaxime is a good candidate for prophylactic use. It has a broad spectrum of activity against gram-negative organisms and shows significant activity against grampositive organisms and anaerobes. Within 10 minutes of intravenous injection, it reaches plasma concentrations in excess of the minimal inhibitory concentration values of many common pathogens [1,2]. Cefotaxime is widely distributed in body fluids and has an active metabolite with a half-life and bactericidal action that consistently enhance parent drug potency. The studies carried out in recent years have been influenced by specialized centers that have laid the foundations for a change from short-term to single-dose prophylaxis. Cefotaxime is well established in multipledose perioperative prophylactic use and has shown significant benefits when compared with no prophylaxis, especially in urologic surgery [3,4]. Comparisons with other antibiotics have shown the equal prophylactic activity of cefotaxime [5-7], and also of single-dose cefotaxime versus multiple-dose cephalosporin [8-11]. Current practice favors short-term rather than longterm prophylaxis, with the obvious advantages of convenience, lower cost [4,8,12], and lower incidence of resistant bacterial strains [4, 8]. The object of this study was to compare the efficacy and safety of two schedules of prophylactic cefotaxime in abdominal, gynecologic, and urologic surgery. PATIENTS AND METHODS A total of 3,670 patients undergoing general abdominal, urologic, and gynecologic surgical procedures were recruited between January 1, 1990, and June 30, 1991, in 226 Italian surgical units. The executive coordinator was Dr. P. Muiesan, Surgery Clinic, University of Brescia. Each surgical unit treated between 10 and 20 patients, each of whom was randomized to one of the two treatment schedules on an open basis. Patient selection: Patients of either gender and any age were recruited prior to undergoing the following categories of surgical procedure: abdominal (gastroduodenal, small bowel including appendectomy, hepatobiliary), gynecologic (abdominal and vaginal hysterectomy and myomectomy), and urologic (all types except transurethral resection).
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The exclusion criteria were: known or suspected I~-lactam sensitivity, treatment with any antibiotic in the 7 days preceding surgery, requirement for combination antibiotic treatment resulting from the nature of the patient's condition or type of surgical procedure (e.g., immunosuppression or colorectal surgery), or terminal illness. All patients gave informed consent and the study complied with the 18th World Medical Congress guidelines (Helsinki, 1964; Venice amendments, 1983) and was approved by each hospital's ethical committee. T r e a t m e n t schedules: Schedule A patients received 1 g of cefotaxime (Roussel Pharma/Hoechst Italia, Milan) intravenously 30 minutes before incision. This might be repeated in 6 hours if the operation lasted more than 3 hours. Schedule B patients received 1 g of cefotaxime intravenously 30 minutes before incision and two 1-g doses intravenously at 6-hour intervals after the first. This was performed on an intention-to-treat basis, given the constraints of operating room practice. Investigations: All evaluations and laboratory analyses, before and after the investigation, were recorded on the clinical case report form. Patient information comprised age, gender, weight, height, and allergies. Risk factors (malnutrition, anemia, debilitating illness, immunosuppression, diabetes, and obesity), concurrent illness, and non-antibiotic drug therapies were recorded. Laboratory investigations (blood: hemoglobin, white cell count and differential, platelets, erythrocyte sedimentation, liver function tests, and serum electrolytes; urine: protein, glucose, and sediment) were performed as part of general patient care, but were not incorporated in the analysis of the study results. In each case the type and duration of the operation was recorded together with time(s) of antibiotic administration. Follow-up time was 7 days or until discharge, whichever occurred first. If postoperative hospital stay was prolonged, then the reason was specified. Completed case-report forms were sent to the coordinator for evaluation. E v a l u a t i o n e r i t e r i a : EFFICACY: Outcome was assessed using the following five criteria: (a) discharge of serous or seropurulent material from the wound within 7 days of operation; (b) pyrexia (axillary temperature > 37.5~ within 48 hours of operation; (c) prolongation of hospital stay resulting from criteria (a) and/or (b); (d) bacteriuria ( > 100,000 organisms/mL); and (e) need for antibiotic treatment within 7 days of operation. SAFETY AND ACCEPTABILITY: Safety and acceptability were assessed in three categories (good, fair, and unsatisfactory) with respect to both local (thrombophlebitis) and systemic side effects on the two treatment schedules. The systemic effects assessed were allergic reaction and severe gastrointestinal upset. Statistics: Statistical analysis was performed using SPSS software on a Macintosh personal computer. The two treatment groups were compared using contingency tables and the chi-square test with Yates' correction. In
TABLE I Incidence of Wound Infection per Treatment Group and Type of Surgery Surgery
Total
Wound Infection
p-Value*
Abdominal
A B
1,132 1,361
11 33
0.09
Gynecologic
A B
385 223
12 4
0.53
Urologic
A B
285 181
5 2
n.s.t
All types
A B
1,802 1,765
28 39
0.18
*Chi-square test. tFisher's exact test; n.s. = not significant at the 5% confidence interval.
TABLE II Incidence of Postoperative Bacteriuria per Treatment Group and Type of Surgery Surgery
Total
Bacteriuria
p-Value*
Abdominal
A B
664 890
5 7
1.0
Gynecologic
A B
377 139
11 7
0.64
Urologic
A B
237 129
4 0
n.s.t
All types
A B
1,278 1,158
20 14
0.65
*Chi-square test. tFisher's exact test, n.s. = not significant at the 5% confidence interval.
those cases that involved less than five per cell, Fisher's exact test was used. Wilcoxon's rank sum test was used for nonparametric ranked comparisons. RESULTS The study comprised 3,670 patients, aged 2-97 years (mean 45.1). Schedule A was used in 1,832 patients (62% abdominal, 22% gynecologic, and 16% urologic surgery). Schedule B was used in 1,838 patients (76% abdominal, 12% gynecologic, and 12% urologic surgery). The proportion of schedule A patients requiring a second dose of cefotaxime because the duration of surgery exceeded 3 hours was 99/1,145 (abdominal), 20/391 (gynecologic), and 12/296 (urologic). The average (range) of surgery duration (minutes) for abdominal were schedule A = 63 (10-300), schedule B = 80 (100 430); for gynecologic schedule A = 90 (25-240), schedule B = 84 (20~ and for urologic schedule A = 60 (10-290), schedule B = 63 (5-360). Effieaey: No difference was detected in the frequency of wound infection and bacteriuria in the two treatment schedules after an overall analysis and after considered by category of surgery (Tables I and II).
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TABLE III Incidence of Postoperative Pyrexia per Treatment Group and Type of Surgery Surgery
Total
Pyrexia
p-Value*
Abdominal
A B
1,132 1,361
124 247
0.0011.
Gynecologic
A B
382 221
55 47
0.041-
Urologic
A B
283 180
18 18
0.21
All types
A B
1,798 1,758
197 312
0.0011-
*Chi-square test. tSignificant at the 5% level.
TABLE IV Number of Patients Requiring Additional Postoperative Antibiotics per Treatment Group and Type of Surgery Additional Surgery Abdominal
A B A B A B A B
Gynecologic Urologic All types
Total
Antibiotics
1,102 1,316 377 216 278 180 1,757 1,712
53 95 27 26 13 15 93 136
p-Value* 0.01t 0.06 0.16 0.002t
*Chi-square test. l-Significant at the 5% level.
TABLE V Number of Patients Requiring a Prolonged Hospital Stay per Treatment Group and Type of Surgery Surgery
Total
Prolonged Stay
p-Value*
Abdominal
A B
1,130 1,359
41 83
0.011-
Gynecologic
A B
378 223
22 8
0.31
Urologic
A B
284 179
12 8
1.0
All types
A B
1,792 1,761
75 99
0.051-
*Chi-square test. "i-Significant at the 5% level.
There was a significantly greater frequency of postoperative pyrexia and need for additional antibiotic treatment in schedule B compared with schedule A. This difference was only demonstrated in abdominal and gynecologic surgery, not in urologic surgery (Tables III
and IV). There were significantly more patients on schedule B requiring a prolonged hospital stay but this was confined to the abdominal surgery group (Table V). 18S
Safety and acceptability: Within schedules A and B, 1,794 and 1,708 patients, respectively, were evaluated for the appearance of systemic side effects. In each group all but 20 reported good acceptability and there was no unsatisfactory report. Local side effects were evaluated in 1,700 patients on schedule A and 1,517 cases on schedule B; one unsatisfactory and 9 fair reports were in the schedule A group, versus 2 unsatisfactory and 38 fair reports in the schedule B group. Thus, schedule B produced more local side effects (Wilcoxon rank sum: W = 2,412,925.5; p < 0.05). DISCUSSION Postoperative infection is a common complication associated with surgical procedures. A recent multicenter surgical study [13] found 565 infective episodes (60% gram-negative) in 11,363 patients. That incidence of 5%, taken as a historical control, compared with the observed incidences of wound infections in this study of approximately 2%, suggests definite benefit. Other investigators have reported a reduction in postoperative infection from 46% to 5% in open prostatectomy and from 13% to 0% in biliary surgery [4,14]. Both of these studies were placebo-controlled. This observation might be of particular importance to patients with specific risk factors, such as malnutrition, who appear to gain a greater protective effect from prophylaxis than well-nourished controls [15]. In the present study, no difference was shown between the two treatment schedules in terms of wound infection, thus justifying the use of single-dose prophylaxis. However, the increased frequency of postoperative pyrexia and need for additional antibiotics associated with triple-dose prophylaxis (schedule B) demonstrated an appreciable advantage with the single-dose schedule A. This advantage is probably the result of the single dose not disturbing the organic equilibrium, while having an immediate effect on the multiplication and adhesivity of circulating bacteria. The advantage of the single-dose regimen was also seen with respect to duration of hospital stay and local side effects. The causes of prolonged stay encompassed many factors other than the prophylaxis regimen, but < 10% in either treatment schedule was attributable to infection. It seems unlikely that the observed difference can be causally related to the type of prophylaxis. The lower frequency of pyrexia, most noticeable in the abdominal surgery group, was not explained by shorter operation time and should be free of bias because of the random allocation of treatment schedules in the different participating centers. The study is continuing, and it is hoped that this point might be clarified by the further information that is accruing from the different centers. No serious side effect was encountered and only one case (urticaria) was considered a definite reaction to cefotaxime. However, the increased number of local effects (thrombophlebitis) associated with schedule B might be simply explained by the three fold number of
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2a, Osp V Emanuele, CATANtA;Prof G D'Ambrosio, Prim Rep Chir 3a, Osp Civ, TREVISO;Prof D D'Amico, Dir 2a Clin Chir, University, PADUA;Prof B D'Errico, Prim Rep Chir, Osp Civ, GALATINA;ProfF Dall'Antonia, Prim Rep Chir la, Osp Gen VICENZA;DR S Danero, Clinica Ostet, SIENA;Dr E De Sanctis, Prim Rep Chit Ia, Osp Gen Reg, RIET1;Dr F D'Elia, 56023 NAVACCHIO--PI;Dr D Do, 10022 CARMAGNOLA--TO;Dr F Dolci, Prim Rep Ostet, Osp Civ, SONDRIO; Dr G Ducci, Rep Chir, Osp di Circolo, CANTU;Prof R Esposito, Prim Rep Chir, Osp Civ, MAGLIE;Prof P Fabrucci, 50063 FIGLINE VALDARNO-FI;Prof A Fantoni, Prim Rep Chir 2a, Osp Maggiore, BERGAMO;Dr W Favale, 00049 VELLETRI-ROMA;Dr P Favro, Prim Div Urol, Osp Civ, NOVARA;Dr P Fedole, Rep Chir, Osp Civ, MARTINAFRANCA;Dr D Ferrante, 86100 NAPOLI;Prof M Ferrari, 64021 GIULIAVONA--TE;DrG Finocchiaro, 24065 LOVERE-BG;Prof L Forlivesi, 47037 RIMIN1--FO;Prof S. Forti, Rep Chir 1a, Osp Valduce, COMO;Dr G C Fossati, RIVOLI-TO;Dr F Francomano, Ist Patol Chir, Osp Riuniti, CHIETI; Dr M Franzini, Prim Chir Gen, Osp Civ, GUASTALLA;Dr M Fraquelli, Prim Div Chir, Osp Civile, CARATEBRIANZA;Dr A Frugoni, 17100 SAVONA;Prof A Fumarola, Div Chir, Osp Civ, CAMERINO;Dr B Gaetano, 00144 ROMA;Dr M Gardini, Prim Div Chir Gen, LUGO;Dr M Garofalo, Div Urol 2a, Osp Malpighi, BOLOGNA;Prof A Gastaldi, Dir Clin Ostet, Osp Gen Reg, BRESCIA;Prof G Gelmi, 36075 MONTECCHIOMAGGIORE--V1;Dr G Gentili, Rep Chir Gen, Osp Civ, VELLETRI;Dr L Giani, Rep MULTICENTER STUDY GROUP Chir, Osp Civ, GRAVEDONA;Dr G Giorgio, 70022 ALTAMURA--BA; Multicenter Study Group members are as follows: Prof A Prof D Giubilei, 00019 TIVOLI-ROMA;Prof P A Goffrini, Dir Clin Agresti, 81038 NAPOLI; Dr G Agus, 09016 iGLESIAS--CA;Prof G Chri, PARMA;Dr L Graziano, 13019 VARALLOSESlA-VC; Prof A Alagni, Rep Chir, Osp Civ, GORIZIA;Dr F S Amato, 80059 TORRE Greco, 24058 ROMANOD1 LOMBARDIA-BG;Dr C Gualerzi, 42027 DEL GRECO-NA;Prof A Ambrosini, 20077 MELEGNANO-MI;Prof E MONTECCH10 EMILIA-RE; Prof S Guazzieri, 32100 BELLUNO;Prof Amenta, Clin Chir 3a, Policl S Orsola, BOLOGNA;Dr G Amodeo, M Iaccarino, Prim Ostet, Osp Loreto Mare, NAPOL1;Dr G Iannello, Osp Buccheri La Fora, PALERMO;Prof E Ancona, 35100 eADOVA; 87018 S MARCOARGENTANO-CS;ProfA Innocenzi, 10064 PINEROLOProf A Andrei, 16016 COGOLETO--GE;Prof A Anello, Prim Div TO; Prof A Leggeri, Dir Ist Patol Spec Chit, CATFINARA;Dr C de Urol, Osp Villa Sofia, pALERMO;Prof A Anfossi, Prim Rep Chir, Lellis, 88100 CATANZARO;Dr L Leone, 96100 SIRACUSA;Dr R Levi Osp Civ, ALBENGA;Prof G F Anselmetti, 10141 TORINO; Dr F d'Ancona, 34126 TRIESTE;Prof M Lise, Patol Chit 3a, University, dell'Aquila, 70051 BARLETTA-BA;Dr I Ardovino, 82100 BENEVEN- PADOVA; Prof L Lolli, 06049 SPOLETO-PG; Dr M Losco, 75100 To;Dr O Argentieri, 66026 ORTONA-CH;Prof S Armenio, Dir Ist MnTERA; Dr F Lucchesi, 55100 LUCCA;Prof F Lucchetti, Osp SS Patol Chit, Loc Le Scotte, SIENA;Prof A Baion, 52100 AREZZO;Dr Sacramento, CECCANO;Dr A Macaluso, 90127 PALERMO;Prof G G Ballabio, 00193 ROMA;Prof G Bartolotta, Prim Rep Urol, Osp Macaluso, Prim Rep Urol, Osp Riun, PARM; Dr R O Mainiero, Gravina, CALTAGIRONE;Dr E Bartolucci, Rep Chir, Osp Civ, 07026 OLBIA-SS;Dr G Maione, Rep Urol, Osp Polispec, ANZIO;Dr FOSSOMBRONE;Prof A Bayon, Prim 2a Div Chir, Osp Gen Prof, C Maiorca, Prim Rep Chir, Nuovo Osp, MESSINA;Prof A Maisano, AREZZO; Prof B Becca, Prim Div Ost Ginecol, Osp S M Croci, Prim Rep Chir, Osp Gen Zona, TARQUINIA;Dr C Malaspina, 22100 RAVENNA;Prof G Becchi, Rep Chit, Osp Civ, GENOASAMPIER- COMO;Prof G Maltoni, Prim Div Urol, Osp Morgagni, FORLI;Dr P DARENA;Prof F Belbusti, 61029 URBINO--FS;Prof G F Berizzi, 20121 Manca, Rep Chir, Osp Sirai, CARBONIA;Dr G Mantovani, 20066 M1LANO; Prof G Bernardini, 19038 SARZANA-SP;Prof D Bertini, MELZO--MI;Dr E Marchese, Rep Chir, Osp Civ, LANCIANO;Prof L Chir Gen, Osp Careggi, FIRENZE;Prof U Bianchi, Dir Clin Ostet E Marinelli, Prim Chir Plast, Osp S Eugenio, ROME; Dr R Osp Civ Brescia; Dr F Boglietti, 10064 PINEROLO-TO;Prof A Maruotti, Prim Rep Chir, Osp Civ, ABB1ATEGRASSO;Dr C MaterBonomo, 00186 ROMA; Prof M Bonoma, Dir Clin Chir d'Urg, nini, 22100 COMO; Prof N Mezzatesta, 90127 PALERMO;Prof F Policl, BARI; Dr S Bortoli, 40046 PORRETTATERME--BO; Dr A Milanesi, 10073 CIRIE--TO;Dr C Milani, Prim Rep Urol, Osp Civ, Brendolan, 36071 ARZIGNANO--VI;Prof F Bresadola, 33100 UDINE; VIMERCATE;Dr G Minervini, Rep Chir, Osp Civ, MOLFETrA;Dr F Prof G Brotzu, Dir Clin Chir 2a, CAGLIARI;Prof C Buccellato, Minetti, Prim Rep Ostet, Osp Gen Prov, MESTRE;Prof D Molino, 90132 PALERMO;Dr G Calderini, 03043 CASSINO--FR;ProfA Campan- 80127 NAPOLI;Prof V Molicca, 44100 FERRARA;Dr G B Morandi, elli, 80127 NAPOLI;Prof M Camurri, Prim Div, Osp Civ, CARPI;Prof Rep Chir, Osp Civ, ISEO;Prof F Morino, Dir Clin Chir Gen, TURIN; A Canerini, Prim Rep Urol, Ist Regina Elena, ROMA; Prof V Dr C Morrone, 87075 TREBISACCE--CS;Prof F Mosca, 56122 PISA; Canino, 10144 TORINO;Dr G de Capua, 84087 SARNO--SA;Prof G Prof R Motta, Prim la Div Chir, Osp S M Nuova, REGGIOE; Dr A Caraffa, Div Chir, Osp Gen Zona, DESIO;Prof A Carli, Dir Ist Sem Mundula, 07014 OZIERI-SS; Prof A Nemeth, Dir Patol Chir, EOR, Chir, Policlinico, SIENA; Dr A Di Caro, 16164 GENOVA; Dr O TRIESTE; Prof P Nocentini, la Rep Chir, FLORENCE;Dr S Orsini, Cartia, Prim Rep Chir, Osp Civ, CUNEO; Dr P Caruana, 92100 03026 ISOLAOEL LIRI--ER;Prof F Paccione, Dir Pat Chir Spec 2a, AGRIGENTO;Prof M Casaccia, 16132 GENOVA;Prof U C Casciani, Policl, BARI; Dr U Palladino, 81055 s MARIA C V--CE; Dr F Dir 5a Pat Chit, II Univ Tor Vergata, ROMA; Dr E Casini Ropa, Panebianco, Div Chir, Osp Tomaselli, CATANIA;Prof G Paolucci, 60033 CHIARAVALLE--AN;Dr E Casolari, Rep Urol, Osp S M Nuova, 62013 MACERATA;Dr G Pasini, 48018 FAENZA-RA;Prof V Pati, Rep REGGIO E; Dr G B Cassinelli, Prim Div Chir 1a, Osp Maggiore, Urol, Osp S Giovanni, ROMA;Prof P Pellegrini, 70012 CARBONARABERGAMO;Dr S Castellucci, 61043 CAGLI--PS;Dr F Catizono, Prim BA; Dr G Perrotta, 87028 PRA/AAL MARE-CS;Dr G P Petrelli, 36012 Rep Ostet, Osp Civ, ROSSANOCALABRO;Dr M Cavarzere, Div Urol, ASIAGO--VI;Prof C Petrin, Prim Rep Chir, Ente Ospedal, DOLO;Dr Osp Gen Prov, LEGNAGO;Prof A Caviglia, 00152 ROMA; Dr P P V Pezzangora, Prim Rep Chit, Osp Civ, CHIOGGIA;Prof V Piegari, Chessa, Prim Chir, Osp Sirai, CARBONIA;Dr A Ciccarelli, 83031 80138 NAPOLI;Dr F Pitrelli, 74100 TARANTO;Dr S Pizza, Div Chir ARIANOIRPINO-AV;Dr L Cimmino, 80076 LACCOAMENO--NA;Dr A Ia, Arcisp S M Nuova, FLORENCE;Dr C Platania, 95040 RAMACCA-Coda, Osp Gradenico, Rep Chir, TOR1NO;Prof R Conte, 80142 CT; Dr R Polimeni, Rep Chit 2a, Osp Riun, REGGIO C; Dr M NAPOLI;Dr A Conti, Rep Chir 2a, Osp Civ, NOVARA;Prof U Conti, Potestio, Rep Chir, Osp Civ, CUGGIONO;Prof N Presuni, Prim Rep Prim Rep Chir 2a Div, Osp Riun, PIETRALIGURE;Dr F Corongiu, Urol 2a, Osp S Camillo, ROMA;Prof A Properzi, 67100 L'AQUILA; Rep Ost Ginecol, Osp M Vittoria, TORINO;Dr S Cosciani Cunico, Prof F Prosperi, 00152 ROMA;Prof M Proto, 20121 MILANO;Dr V Div Urol, Osp Gen, BRESCIA;Prof B Cramarossa, 72021 FRANCAV- Pugno, Rep Chir, Osp Gen Zona, MONTEFIASCONE;Prof C PullG, 1LEAFONTANA-BR;Prof F Cravarezza, Via S Andrea 20, SAVIGLI- Dir Clin Ostet, Universita, CONTESSO;Dr F Putti, Prim Rep Urol, ANO; Dr L Cucchi, 40038 VERGATO-BO;Prof P Cultrera, Div Chir Osp Gen Prov, ROMA;Prof M Quercio, Rep Chir, Osp S Carlo, i n t r a v e n o u s administrations. R e g a r d i n g safety, cefotaxime has b e e n shown to c o m p a r e well with o t h e r classes of antibiotics [16]. C h o i c e o f antibiotic prophylaxis is i n f l u e n c e d by m a n y factors, including drug safety, site of surgery, t h e p r o b a b l e type of b a c t e r i a l c o n t a m i n a t i o n , and the ability to achieve t h e r a p e u t i c levels in the target tissues during t h e risk period. This m a y be a c c o m p l i s h e d by administering antibiotics singly or in c o m b i n a t i o n , e i t h e r in single d o s e or o v e r a limited period. T h e p o t e n t i a l a d v a n t a g e s of a l o w e r n u m b e r of infections, s h o r t e r hospital stays, and r e d u c e d costs m u s t be b a l a n c e d w i t h the disadvantages o f antibiotic sensitivity, d i s t u r b a n c e o f intestinal flora, and t h e a p p e a r a n c e of resistant strains. O n all t h e s e counts, the results of the p r e s e n t study show that single-dose prophylaxis with c e f o t a x i m e is as effective as the t r i p l e - d o s e r e g i m e n , and t h e single dose is associated with significantly f e w e r side effects.
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GENOAVOLTRI;Dr E Raffaglio, 25063 GARDONEVAL TROMPIA-BS; Prof G Recca, 95047 PATERNO-CT;Prof L Repossini, Rep Chir 2a, Osp, Civile, LEGNANO;DrM Ricotta, 93014 MUSSOMELI--CL;Prof M Rizzo, Dir Catt Patol Urol Ia, FLORENCE;Prof A Robecchi, 28100 NOVAaA;Dr S Rossi, 01037 RONCIGLIONE-VT;Prof M Rubino, Dir Clin Chir, Policl, BARI;Prof S Rugiati, 17100 SAVONA;Dr C Russo, 80014 GIULIANO--NA;Dr V Santorelli, Prim, Osp Civ, VALLODELLA LUCAnIA; Dr R A Schettino, 80059 TORRE DEL GRECO--NA;Dr S Schiliro', 97019 VITTORtA--RG;Prof A Scio, 91100 TRAPANI;Dr G Scollo, 97015 MODICA-RG;Dr N del Secolo, 85025 MELFI-PZ;Prof G Segato, Rep Chir 2a, Osp Gen Reg, VICENZA;Prof F Selvaggi, Dir Cart Urol, Policl, BARI;Prof A Sicari, Div Chir, Osp Gen Prov, CARRARA;Dr L Stabilini, Prim Rep Chir, Osp Civ, NOV1LIGURE;Dr G Straziuso, 85100 POTENZA; Prof G Sturniolo, 98100 MESSINA; Prof C Tagariello, 40024 CASTELS PIETROT--BO;Dr D Tarantini, 70053 CANOSAOI PUGLIA-BA;Dr G Taverniti, 25043 BRENO-BS;Dr D Tedeschi, Div Chir, Osp Civ, PORDENONE;Prof P Tenchini, Prim la Div Chir, Ist Ospedal, MANTUA;Prof E Tendella, Dir Semeiotica Chir, TRIESTE;Prof O Terranova, Prim Div Chir Geriatr, Osp Civ, PADUA; Dr T Teodori, 00018 PALOMBARASABINA-ROMA;Dr R Tessari, 41012 CARPI-MO;Prof G Tiberio, Rep Chir 3a, Osp Gen Reg, BRESCIA;Dr F Tomaselli, 03012 ANAGNI-FR;Dr A Tomassini, Prim Rep Ostet Ginecol, Osp Circolo, TRADATE;Prof P Tombolini, 24040 ZINGONIA--BG;Prof A Travaglini, Div la Chir, Osp Gen Reg, UD1NE; Dr A Tremiterra, Prim Pronto Socc, Osp Umberto I, FROSINONE; Prof C Tremolada, Prim Rep Cbir la, Osp Riun, VENICE; Dr R Trotti, Rep Chir, Osp Civ, ALBENGA;Dr A Tuveri, 09170 ORISTANO;Dr P Vancini, Prim Div Urol, Osp Civ, BUSSOLENGO;Dr R Vasile, 89048 SIDERNOMARINA-RC;Prof C Vassallo, Prim Rep Chir, Osp Civ, STRADELLA;Prof P Ventrice, Prim Rep Urol, Osp Civ, VIBOVALENTIA;Dr T Verrienti, 73039 TRICASE--LE; Dr E de Vincentiis, 80131 NAPOLI;Prof A Vio, Prim Div Chir Gen, Osp Morgagni, FORLI; Prof D Zappavigna, 00165 ROMA; Dr D Zinzi, 81025 MARCIANISE-CE. A c k n o w l e d g m e n t T h e a u t h o r s gratefully acknowle d g e t h e s u p p o r t of R o u s s e l P h a r m a S.p.A. (Viale G r a n Sasso 18, 20131 Milan), H o e c h s t Italia S.p.A. (Via M . U . T r a i a n o 18, 20149 M i l a n ) and t h e c o o p e r a t i o n o f all p a r t i c i p a t i n g surgeons. REFERENCES 1. Periti P, Mazzei T, Costantini A, et al. Comparative pharmacokinetic evaluation of ceftriaxone and cefotaxime in coincidence for short-term antimicrobial prophylaxis in surgery. Chemoterapia 1984; 3: 305-9. 2. White RL, Nightingale CH, Quintiliani P, Whitaker KF, Jones RF 3d, Tripp WH. Serum and tissue concentrations of cefoxitin
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and cefotaxime in women undergoing hysterectomy. Drugs 1988; 35 (Suppl 2): 72-7. 3. Botto H, Richard F, Mathieu F, Perreau AM, Carney M. Short-term prophylaxis with cefotaxime in prostatic surgery. J Antimicrob Chemother 1984; 14 (Suppl B): 231-5. 4. Prokocimer P, Quazza M, Gibert C, et al. Short-term prophylac-
tic antibiotics in patients undergoing prostatectomy: report of a double-blind randomized trial with 2 intravenous doses of cefotaxime. J Urol 1986; 135: 60-4. 5. E1 Mufti MB, Glessa A. Single-dose clavulanate-potentiated amoxycillin versus three-dose cefotaxime in the prevention of wound infection following elective cholecystectomy: J Int Med Res 1988; 16: 92-7. 6. McDonald PJ, Sanders T, Higgins G, et al. Antibiotic prophylaxis in hysterectomy--cefotaxime compared to ampicillin-tinidazole. J Antimicrob Chemother 1984; 14 (Suppl B): 223-30. 7. Periti P, Mazzei T, Lamanna S, Mini E. Single-dose ceftriaxone versus multi-dose cefotaxime as short-term antimicrobial prophylaxis in urologic surgery. Preliminary results of a multicenter prospective randomized study. Chemoterapia 1984; 3: 295-8. 8. Periti P, Mazzei T, Orlandini F, Mini E. Comparison of the antimicrobial prophylactic efficacy of cefotaxime and cephazolin in obstetric and gynaecological surgery. A randomised multicentre study. Drugs 1988; 35 (Suppl 2): 133-8. 9. Roy S, Wilkins J. Single-dose cefotaxime versus 3 to 5 dose cefoxitin for prophylaxis of vaginal or abdominal hysterectomy. J Antimicrob Chemother 1984; 14 (Suppl B): 217-21. 10. Ridley PD, Sagar S. Cephalosporin prophylaxis in abdominal surgery. Br J Clin Pract 1988; 42: 337-42. 1 1. Guyot L. Prophylactic use of cefotaxime in biliary surgery. A prospective multicentre comparison of two dosage regimens. Drugs 1988; 35 (Suppl 2): 158-60. 12. Garcia-Rodriguez JA, Puig-LaCalle J, Arnau C, Porta M, Vallv6 C. Antibiotic prophylaxis with cefotaxime in gastroduodenal and biliary surgery. Am J Surg 1989; 158: 428-32. 13. Privitera G, Auxilia F, Castaldi S, Ortisi G, Pagano A. Epidemiologia e terapia delle infezioni in ambiente chirurgico. (Abstr.) 93rd National Congress (Florence, Oct. 1991), Italian Society of Surgery. 14. Sykes D, Basu PK. Prophylactic use of cefotaxime in elective biliary surgery. J Antimicrob Chemother 1984; 14: 237-9. 15. Di Palo S, Ferrari G, Castoldi R, et al. Effectiveness of antibiotic prophylaxis according to the nutritional status in patients undergoing contaminated procedures. Ital J of Surg Sci 1988; 18: 223-6. 16. Childs SJ, Kosola JW. Update of safety of cefotaxime. Clin Ther 1982; (Suppl A): 97-111.
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Two dose schedules of the antibiotic cefotaxime were c o m p a r e d in a prospective, randomized 2 2 6 center study of 3 , 6 7 0 patients undergoing abdominal, gynecologic, and urologic surgery. Schedule A c o n s i s t e d of a single p r e o p e r a t i v e dose and schedule B consisted of one p r e o p e r a t i v e dose followed by two p o s t o p e r a t i v e doses. T h e r e was no significant difference in the frequency of wound infection or bacteriuria b e t w e e n the two schedules. Schedule B was associated with a significantly higher i n c i d e n c e of postoperative pyrexia, further antibiotic therapy, l o c a l side effects, and e x t e n d e d hospital stay. O n e dose p r o b a b l y has less i m p a c t on the intestinal flora. T h e r e f o r e , single-dose cefotaxime is as effective and less costly when c o m p a r e d with multiple-dose cefotaxime for c o m m o n surgical p r o c e d u r e s lasting less than 3 hours.
From the Istituto di Microbiologia, Universit~t degli Studi di Brescia, Spedali Civili, Piazza Spedali Civili, Brescia, Italy. Requests for reprints should be addressed to Professor Adolfo Turano, Istituto di Microbiologia,Universit~tdegli Studi di Brescia, Spedali Civili, Piazza Spedali Civili, 1, 25100 Brescia, Italy. 16S
he prophylactic use of antibiotics for surgical proce-
T dures has become a standard practice. Surgeons throughout the world recognize the advantages, in virtually all types of procedures, of having a microbiologically active drug available during the critical interval in which bacterial contamination can occur. To achieve this aim, a great variety of antibiotics are currently administered before or during the operation and, if necessary, for some days after the closure of the wound. Cefotaxime is a good candidate for prophylactic use. It has a broad spectrum of activity against gram-negative organisms and shows significant activity against grampositive organisms and anaerobes. Within 10 minutes of intravenous injection, it reaches plasma concentrations in excess of the minimal inhibitory concentration values of many common pathogens [1,2]. Cefotaxime is widely distributed in body fluids and has an active metabolite with a half-life and bactericidal action that consistently enhance parent drug potency. The studies carried out in recent years have been influenced by specialized centers that have laid the foundations for a change from short-term to single-dose prophylaxis. Cefotaxime is well established in multipledose perioperative prophylactic use and has shown significant benefits when compared with no prophylaxis, especially in urologic surgery [3,4]. Comparisons with other antibiotics have shown the equal prophylactic activity of cefotaxime [5-7], and also of single-dose cefotaxime versus multiple-dose cephalosporin [8-11]. Current practice favors short-term rather than longterm prophylaxis, with the obvious advantages of convenience, lower cost [4,8,12], and lower incidence of resistant bacterial strains [4, 8]. The object of this study was to compare the efficacy and safety of two schedules of prophylactic cefotaxime in abdominal, gynecologic, and urologic surgery. PATIENTS AND METHODS A total of 3,670 patients undergoing general abdominal, urologic, and gynecologic surgical procedures were recruited between January 1, 1990, and June 30, 1991, in 226 Italian surgical units. The executive coordinator was Dr. P. Muiesan, Surgery Clinic, University of Brescia. Each surgical unit treated between 10 and 20 patients, each of whom was randomized to one of the two treatment schedules on an open basis. Patient selection: Patients of either gender and any age were recruited prior to undergoing the following categories of surgical procedure: abdominal (gastroduodenal, small bowel including appendectomy, hepatobiliary), gynecologic (abdominal and vaginal hysterectomy and myomectomy), and urologic (all types except transurethral resection).
THE AMERICAN JOURNAL OF SURGERY VOLUME 164 NO. 4A (SUPPL) OCTOBER 1992
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The exclusion criteria were: known or suspected I~-lactam sensitivity, treatment with any antibiotic in the 7 days preceding surgery, requirement for combination antibiotic treatment resulting from the nature of the patient's condition or type of surgical procedure (e.g., immunosuppression or colorectal surgery), or terminal illness. All patients gave informed consent and the study complied with the 18th World Medical Congress guidelines (Helsinki, 1964; Venice amendments, 1983) and was approved by each hospital's ethical committee. T r e a t m e n t schedules: Schedule A patients received 1 g of cefotaxime (Roussel Pharma/Hoechst Italia, Milan) intravenously 30 minutes before incision. This might be repeated in 6 hours if the operation lasted more than 3 hours. Schedule B patients received 1 g of cefotaxime intravenously 30 minutes before incision and two 1-g doses intravenously at 6-hour intervals after the first. This was performed on an intention-to-treat basis, given the constraints of operating room practice. Investigations: All evaluations and laboratory analyses, before and after the investigation, were recorded on the clinical case report form. Patient information comprised age, gender, weight, height, and allergies. Risk factors (malnutrition, anemia, debilitating illness, immunosuppression, diabetes, and obesity), concurrent illness, and non-antibiotic drug therapies were recorded. Laboratory investigations (blood: hemoglobin, white cell count and differential, platelets, erythrocyte sedimentation, liver function tests, and serum electrolytes; urine: protein, glucose, and sediment) were performed as part of general patient care, but were not incorporated in the analysis of the study results. In each case the type and duration of the operation was recorded together with time(s) of antibiotic administration. Follow-up time was 7 days or until discharge, whichever occurred first. If postoperative hospital stay was prolonged, then the reason was specified. Completed case-report forms were sent to the coordinator for evaluation. E v a l u a t i o n e r i t e r i a : EFFICACY: Outcome was assessed using the following five criteria: (a) discharge of serous or seropurulent material from the wound within 7 days of operation; (b) pyrexia (axillary temperature > 37.5~ within 48 hours of operation; (c) prolongation of hospital stay resulting from criteria (a) and/or (b); (d) bacteriuria ( > 100,000 organisms/mL); and (e) need for antibiotic treatment within 7 days of operation. SAFETY AND ACCEPTABILITY: Safety and acceptability were assessed in three categories (good, fair, and unsatisfactory) with respect to both local (thrombophlebitis) and systemic side effects on the two treatment schedules. The systemic effects assessed were allergic reaction and severe gastrointestinal upset. Statistics: Statistical analysis was performed using SPSS software on a Macintosh personal computer. The two treatment groups were compared using contingency tables and the chi-square test with Yates' correction. In
TABLE I Incidence of Wound Infection per Treatment Group and Type of Surgery Surgery
Total
Wound Infection
p-Value*
Abdominal
A B
1,132 1,361
11 33
0.09
Gynecologic
A B
385 223
12 4
0.53
Urologic
A B
285 181
5 2
n.s.t
All types
A B
1,802 1,765
28 39
0.18
*Chi-square test. tFisher's exact test; n.s. = not significant at the 5% confidence interval.
TABLE II Incidence of Postoperative Bacteriuria per Treatment Group and Type of Surgery Surgery
Total
Bacteriuria
p-Value*
Abdominal
A B
664 890
5 7
1.0
Gynecologic
A B
377 139
11 7
0.64
Urologic
A B
237 129
4 0
n.s.t
All types
A B
1,278 1,158
20 14
0.65
*Chi-square test. tFisher's exact test, n.s. = not significant at the 5% confidence interval.
those cases that involved less than five per cell, Fisher's exact test was used. Wilcoxon's rank sum test was used for nonparametric ranked comparisons. RESULTS The study comprised 3,670 patients, aged 2-97 years (mean 45.1). Schedule A was used in 1,832 patients (62% abdominal, 22% gynecologic, and 16% urologic surgery). Schedule B was used in 1,838 patients (76% abdominal, 12% gynecologic, and 12% urologic surgery). The proportion of schedule A patients requiring a second dose of cefotaxime because the duration of surgery exceeded 3 hours was 99/1,145 (abdominal), 20/391 (gynecologic), and 12/296 (urologic). The average (range) of surgery duration (minutes) for abdominal were schedule A = 63 (10-300), schedule B = 80 (100 430); for gynecologic schedule A = 90 (25-240), schedule B = 84 (20~ and for urologic schedule A = 60 (10-290), schedule B = 63 (5-360). Effieaey: No difference was detected in the frequency of wound infection and bacteriuria in the two treatment schedules after an overall analysis and after considered by category of surgery (Tables I and II).
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TABLE III Incidence of Postoperative Pyrexia per Treatment Group and Type of Surgery Surgery
Total
Pyrexia
p-Value*
Abdominal
A B
1,132 1,361
124 247
0.0011.
Gynecologic
A B
382 221
55 47
0.041-
Urologic
A B
283 180
18 18
0.21
All types
A B
1,798 1,758
197 312
0.0011-
*Chi-square test. tSignificant at the 5% level.
TABLE IV Number of Patients Requiring Additional Postoperative Antibiotics per Treatment Group and Type of Surgery Additional Surgery Abdominal
A B A B A B A B
Gynecologic Urologic All types
Total
Antibiotics
1,102 1,316 377 216 278 180 1,757 1,712
53 95 27 26 13 15 93 136
p-Value* 0.01t 0.06 0.16 0.002t
*Chi-square test. l-Significant at the 5% level.
TABLE V Number of Patients Requiring a Prolonged Hospital Stay per Treatment Group and Type of Surgery Surgery
Total
Prolonged Stay
p-Value*
Abdominal
A B
1,130 1,359
41 83
0.011-
Gynecologic
A B
378 223
22 8
0.31
Urologic
A B
284 179
12 8
1.0
All types
A B
1,792 1,761
75 99
0.051-
*Chi-square test. "i-Significant at the 5% level.
There was a significantly greater frequency of postoperative pyrexia and need for additional antibiotic treatment in schedule B compared with schedule A. This difference was only demonstrated in abdominal and gynecologic surgery, not in urologic surgery (Tables III
and IV). There were significantly more patients on schedule B requiring a prolonged hospital stay but this was confined to the abdominal surgery group (Table V). 18S
Safety and acceptability: Within schedules A and B, 1,794 and 1,708 patients, respectively, were evaluated for the appearance of systemic side effects. In each group all but 20 reported good acceptability and there was no unsatisfactory report. Local side effects were evaluated in 1,700 patients on schedule A and 1,517 cases on schedule B; one unsatisfactory and 9 fair reports were in the schedule A group, versus 2 unsatisfactory and 38 fair reports in the schedule B group. Thus, schedule B produced more local side effects (Wilcoxon rank sum: W = 2,412,925.5; p < 0.05). DISCUSSION Postoperative infection is a common complication associated with surgical procedures. A recent multicenter surgical study [13] found 565 infective episodes (60% gram-negative) in 11,363 patients. That incidence of 5%, taken as a historical control, compared with the observed incidences of wound infections in this study of approximately 2%, suggests definite benefit. Other investigators have reported a reduction in postoperative infection from 46% to 5% in open prostatectomy and from 13% to 0% in biliary surgery [4,14]. Both of these studies were placebo-controlled. This observation might be of particular importance to patients with specific risk factors, such as malnutrition, who appear to gain a greater protective effect from prophylaxis than well-nourished controls [15]. In the present study, no difference was shown between the two treatment schedules in terms of wound infection, thus justifying the use of single-dose prophylaxis. However, the increased frequency of postoperative pyrexia and need for additional antibiotics associated with triple-dose prophylaxis (schedule B) demonstrated an appreciable advantage with the single-dose schedule A. This advantage is probably the result of the single dose not disturbing the organic equilibrium, while having an immediate effect on the multiplication and adhesivity of circulating bacteria. The advantage of the single-dose regimen was also seen with respect to duration of hospital stay and local side effects. The causes of prolonged stay encompassed many factors other than the prophylaxis regimen, but < 10% in either treatment schedule was attributable to infection. It seems unlikely that the observed difference can be causally related to the type of prophylaxis. The lower frequency of pyrexia, most noticeable in the abdominal surgery group, was not explained by shorter operation time and should be free of bias because of the random allocation of treatment schedules in the different participating centers. The study is continuing, and it is hoped that this point might be clarified by the further information that is accruing from the different centers. No serious side effect was encountered and only one case (urticaria) was considered a definite reaction to cefotaxime. However, the increased number of local effects (thrombophlebitis) associated with schedule B might be simply explained by the three fold number of
THE AMERICAN JOURNAL OF SURGERY VOLUME 164 NO. 4A (SUPPL) OCTOBER 1992
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2a, Osp V Emanuele, CATANtA;Prof G D'Ambrosio, Prim Rep Chir 3a, Osp Civ, TREVISO;Prof D D'Amico, Dir 2a Clin Chir, University, PADUA;Prof B D'Errico, Prim Rep Chir, Osp Civ, GALATINA;ProfF Dall'Antonia, Prim Rep Chir la, Osp Gen VICENZA;DR S Danero, Clinica Ostet, SIENA;Dr E De Sanctis, Prim Rep Chit Ia, Osp Gen Reg, RIET1;Dr F D'Elia, 56023 NAVACCHIO--PI;Dr D Do, 10022 CARMAGNOLA--TO;Dr F Dolci, Prim Rep Ostet, Osp Civ, SONDRIO; Dr G Ducci, Rep Chir, Osp di Circolo, CANTU;Prof R Esposito, Prim Rep Chir, Osp Civ, MAGLIE;Prof P Fabrucci, 50063 FIGLINE VALDARNO-FI;Prof A Fantoni, Prim Rep Chir 2a, Osp Maggiore, BERGAMO;Dr W Favale, 00049 VELLETRI-ROMA;Dr P Favro, Prim Div Urol, Osp Civ, NOVARA;Dr P Fedole, Rep Chir, Osp Civ, MARTINAFRANCA;Dr D Ferrante, 86100 NAPOLI;Prof M Ferrari, 64021 GIULIAVONA--TE;DrG Finocchiaro, 24065 LOVERE-BG;Prof L Forlivesi, 47037 RIMIN1--FO;Prof S. Forti, Rep Chir 1a, Osp Valduce, COMO;Dr G C Fossati, RIVOLI-TO;Dr F Francomano, Ist Patol Chir, Osp Riuniti, CHIETI; Dr M Franzini, Prim Chir Gen, Osp Civ, GUASTALLA;Dr M Fraquelli, Prim Div Chir, Osp Civile, CARATEBRIANZA;Dr A Frugoni, 17100 SAVONA;Prof A Fumarola, Div Chir, Osp Civ, CAMERINO;Dr B Gaetano, 00144 ROMA;Dr M Gardini, Prim Div Chir Gen, LUGO;Dr M Garofalo, Div Urol 2a, Osp Malpighi, BOLOGNA;Prof A Gastaldi, Dir Clin Ostet, Osp Gen Reg, BRESCIA;Prof G Gelmi, 36075 MONTECCHIOMAGGIORE--V1;Dr G Gentili, Rep Chir Gen, Osp Civ, VELLETRI;Dr L Giani, Rep MULTICENTER STUDY GROUP Chir, Osp Civ, GRAVEDONA;Dr G Giorgio, 70022 ALTAMURA--BA; Multicenter Study Group members are as follows: Prof A Prof D Giubilei, 00019 TIVOLI-ROMA;Prof P A Goffrini, Dir Clin Agresti, 81038 NAPOLI; Dr G Agus, 09016 iGLESIAS--CA;Prof G Chri, PARMA;Dr L Graziano, 13019 VARALLOSESlA-VC; Prof A Alagni, Rep Chir, Osp Civ, GORIZIA;Dr F S Amato, 80059 TORRE Greco, 24058 ROMANOD1 LOMBARDIA-BG;Dr C Gualerzi, 42027 DEL GRECO-NA;Prof A Ambrosini, 20077 MELEGNANO-MI;Prof E MONTECCH10 EMILIA-RE; Prof S Guazzieri, 32100 BELLUNO;Prof Amenta, Clin Chir 3a, Policl S Orsola, BOLOGNA;Dr G Amodeo, M Iaccarino, Prim Ostet, Osp Loreto Mare, NAPOL1;Dr G Iannello, Osp Buccheri La Fora, PALERMO;Prof E Ancona, 35100 eADOVA; 87018 S MARCOARGENTANO-CS;ProfA Innocenzi, 10064 PINEROLOProf A Andrei, 16016 COGOLETO--GE;Prof A Anello, Prim Div TO; Prof A Leggeri, Dir Ist Patol Spec Chit, CATFINARA;Dr C de Urol, Osp Villa Sofia, pALERMO;Prof A Anfossi, Prim Rep Chir, Lellis, 88100 CATANZARO;Dr L Leone, 96100 SIRACUSA;Dr R Levi Osp Civ, ALBENGA;Prof G F Anselmetti, 10141 TORINO; Dr F d'Ancona, 34126 TRIESTE;Prof M Lise, Patol Chit 3a, University, dell'Aquila, 70051 BARLETTA-BA;Dr I Ardovino, 82100 BENEVEN- PADOVA; Prof L Lolli, 06049 SPOLETO-PG; Dr M Losco, 75100 To;Dr O Argentieri, 66026 ORTONA-CH;Prof S Armenio, Dir Ist MnTERA; Dr F Lucchesi, 55100 LUCCA;Prof F Lucchetti, Osp SS Patol Chit, Loc Le Scotte, SIENA;Prof A Baion, 52100 AREZZO;Dr Sacramento, CECCANO;Dr A Macaluso, 90127 PALERMO;Prof G G Ballabio, 00193 ROMA;Prof G Bartolotta, Prim Rep Urol, Osp Macaluso, Prim Rep Urol, Osp Riun, PARM; Dr R O Mainiero, Gravina, CALTAGIRONE;Dr E Bartolucci, Rep Chir, Osp Civ, 07026 OLBIA-SS;Dr G Maione, Rep Urol, Osp Polispec, ANZIO;Dr FOSSOMBRONE;Prof A Bayon, Prim 2a Div Chir, Osp Gen Prof, C Maiorca, Prim Rep Chir, Nuovo Osp, MESSINA;Prof A Maisano, AREZZO; Prof B Becca, Prim Div Ost Ginecol, Osp S M Croci, Prim Rep Chir, Osp Gen Zona, TARQUINIA;Dr C Malaspina, 22100 RAVENNA;Prof G Becchi, Rep Chit, Osp Civ, GENOASAMPIER- COMO;Prof G Maltoni, Prim Div Urol, Osp Morgagni, FORLI;Dr P DARENA;Prof F Belbusti, 61029 URBINO--FS;Prof G F Berizzi, 20121 Manca, Rep Chir, Osp Sirai, CARBONIA;Dr G Mantovani, 20066 M1LANO; Prof G Bernardini, 19038 SARZANA-SP;Prof D Bertini, MELZO--MI;Dr E Marchese, Rep Chir, Osp Civ, LANCIANO;Prof L Chir Gen, Osp Careggi, FIRENZE;Prof U Bianchi, Dir Clin Ostet E Marinelli, Prim Chir Plast, Osp S Eugenio, ROME; Dr R Osp Civ Brescia; Dr F Boglietti, 10064 PINEROLO-TO;Prof A Maruotti, Prim Rep Chir, Osp Civ, ABB1ATEGRASSO;Dr C MaterBonomo, 00186 ROMA; Prof M Bonoma, Dir Clin Chir d'Urg, nini, 22100 COMO; Prof N Mezzatesta, 90127 PALERMO;Prof F Policl, BARI; Dr S Bortoli, 40046 PORRETTATERME--BO; Dr A Milanesi, 10073 CIRIE--TO;Dr C Milani, Prim Rep Urol, Osp Civ, Brendolan, 36071 ARZIGNANO--VI;Prof F Bresadola, 33100 UDINE; VIMERCATE;Dr G Minervini, Rep Chir, Osp Civ, MOLFETrA;Dr F Prof G Brotzu, Dir Clin Chir 2a, CAGLIARI;Prof C Buccellato, Minetti, Prim Rep Ostet, Osp Gen Prov, MESTRE;Prof D Molino, 90132 PALERMO;Dr G Calderini, 03043 CASSINO--FR;ProfA Campan- 80127 NAPOLI;Prof V Molicca, 44100 FERRARA;Dr G B Morandi, elli, 80127 NAPOLI;Prof M Camurri, Prim Div, Osp Civ, CARPI;Prof Rep Chir, Osp Civ, ISEO;Prof F Morino, Dir Clin Chir Gen, TURIN; A Canerini, Prim Rep Urol, Ist Regina Elena, ROMA; Prof V Dr C Morrone, 87075 TREBISACCE--CS;Prof F Mosca, 56122 PISA; Canino, 10144 TORINO;Dr G de Capua, 84087 SARNO--SA;Prof G Prof R Motta, Prim la Div Chir, Osp S M Nuova, REGGIOE; Dr A Caraffa, Div Chir, Osp Gen Zona, DESIO;Prof A Carli, Dir Ist Sem Mundula, 07014 OZIERI-SS; Prof A Nemeth, Dir Patol Chir, EOR, Chir, Policlinico, SIENA; Dr A Di Caro, 16164 GENOVA; Dr O TRIESTE; Prof P Nocentini, la Rep Chir, FLORENCE;Dr S Orsini, Cartia, Prim Rep Chir, Osp Civ, CUNEO; Dr P Caruana, 92100 03026 ISOLAOEL LIRI--ER;Prof F Paccione, Dir Pat Chir Spec 2a, AGRIGENTO;Prof M Casaccia, 16132 GENOVA;Prof U C Casciani, Policl, BARI; Dr U Palladino, 81055 s MARIA C V--CE; Dr F Dir 5a Pat Chit, II Univ Tor Vergata, ROMA; Dr E Casini Ropa, Panebianco, Div Chir, Osp Tomaselli, CATANIA;Prof G Paolucci, 60033 CHIARAVALLE--AN;Dr E Casolari, Rep Urol, Osp S M Nuova, 62013 MACERATA;Dr G Pasini, 48018 FAENZA-RA;Prof V Pati, Rep REGGIO E; Dr G B Cassinelli, Prim Div Chir 1a, Osp Maggiore, Urol, Osp S Giovanni, ROMA;Prof P Pellegrini, 70012 CARBONARABERGAMO;Dr S Castellucci, 61043 CAGLI--PS;Dr F Catizono, Prim BA; Dr G Perrotta, 87028 PRA/AAL MARE-CS;Dr G P Petrelli, 36012 Rep Ostet, Osp Civ, ROSSANOCALABRO;Dr M Cavarzere, Div Urol, ASIAGO--VI;Prof C Petrin, Prim Rep Chir, Ente Ospedal, DOLO;Dr Osp Gen Prov, LEGNAGO;Prof A Caviglia, 00152 ROMA; Dr P P V Pezzangora, Prim Rep Chit, Osp Civ, CHIOGGIA;Prof V Piegari, Chessa, Prim Chir, Osp Sirai, CARBONIA;Dr A Ciccarelli, 83031 80138 NAPOLI;Dr F Pitrelli, 74100 TARANTO;Dr S Pizza, Div Chir ARIANOIRPINO-AV;Dr L Cimmino, 80076 LACCOAMENO--NA;Dr A Ia, Arcisp S M Nuova, FLORENCE;Dr C Platania, 95040 RAMACCA-Coda, Osp Gradenico, Rep Chir, TOR1NO;Prof R Conte, 80142 CT; Dr R Polimeni, Rep Chit 2a, Osp Riun, REGGIO C; Dr M NAPOLI;Dr A Conti, Rep Chir 2a, Osp Civ, NOVARA;Prof U Conti, Potestio, Rep Chir, Osp Civ, CUGGIONO;Prof N Presuni, Prim Rep Prim Rep Chir 2a Div, Osp Riun, PIETRALIGURE;Dr F Corongiu, Urol 2a, Osp S Camillo, ROMA;Prof A Properzi, 67100 L'AQUILA; Rep Ost Ginecol, Osp M Vittoria, TORINO;Dr S Cosciani Cunico, Prof F Prosperi, 00152 ROMA;Prof M Proto, 20121 MILANO;Dr V Div Urol, Osp Gen, BRESCIA;Prof B Cramarossa, 72021 FRANCAV- Pugno, Rep Chir, Osp Gen Zona, MONTEFIASCONE;Prof C PullG, 1LEAFONTANA-BR;Prof F Cravarezza, Via S Andrea 20, SAVIGLI- Dir Clin Ostet, Universita, CONTESSO;Dr F Putti, Prim Rep Urol, ANO; Dr L Cucchi, 40038 VERGATO-BO;Prof P Cultrera, Div Chir Osp Gen Prov, ROMA;Prof M Quercio, Rep Chir, Osp S Carlo, i n t r a v e n o u s administrations. R e g a r d i n g safety, cefotaxime has b e e n shown to c o m p a r e well with o t h e r classes of antibiotics [16]. C h o i c e o f antibiotic prophylaxis is i n f l u e n c e d by m a n y factors, including drug safety, site of surgery, t h e p r o b a b l e type of b a c t e r i a l c o n t a m i n a t i o n , and the ability to achieve t h e r a p e u t i c levels in the target tissues during t h e risk period. This m a y be a c c o m p l i s h e d by administering antibiotics singly or in c o m b i n a t i o n , e i t h e r in single d o s e or o v e r a limited period. T h e p o t e n t i a l a d v a n t a g e s of a l o w e r n u m b e r of infections, s h o r t e r hospital stays, and r e d u c e d costs m u s t be b a l a n c e d w i t h the disadvantages o f antibiotic sensitivity, d i s t u r b a n c e o f intestinal flora, and t h e a p p e a r a n c e of resistant strains. O n all t h e s e counts, the results of the p r e s e n t study show that single-dose prophylaxis with c e f o t a x i m e is as effective as the t r i p l e - d o s e r e g i m e n , and t h e single dose is associated with significantly f e w e r side effects.
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MULTICENTER STUDY GROUP
GENOAVOLTRI;Dr E Raffaglio, 25063 GARDONEVAL TROMPIA-BS; Prof G Recca, 95047 PATERNO-CT;Prof L Repossini, Rep Chir 2a, Osp, Civile, LEGNANO;DrM Ricotta, 93014 MUSSOMELI--CL;Prof M Rizzo, Dir Catt Patol Urol Ia, FLORENCE;Prof A Robecchi, 28100 NOVAaA;Dr S Rossi, 01037 RONCIGLIONE-VT;Prof M Rubino, Dir Clin Chir, Policl, BARI;Prof S Rugiati, 17100 SAVONA;Dr C Russo, 80014 GIULIANO--NA;Dr V Santorelli, Prim, Osp Civ, VALLODELLA LUCAnIA; Dr R A Schettino, 80059 TORRE DEL GRECO--NA;Dr S Schiliro', 97019 VITTORtA--RG;Prof A Scio, 91100 TRAPANI;Dr G Scollo, 97015 MODICA-RG;Dr N del Secolo, 85025 MELFI-PZ;Prof G Segato, Rep Chir 2a, Osp Gen Reg, VICENZA;Prof F Selvaggi, Dir Cart Urol, Policl, BARI;Prof A Sicari, Div Chir, Osp Gen Prov, CARRARA;Dr L Stabilini, Prim Rep Chir, Osp Civ, NOV1LIGURE;Dr G Straziuso, 85100 POTENZA; Prof G Sturniolo, 98100 MESSINA; Prof C Tagariello, 40024 CASTELS PIETROT--BO;Dr D Tarantini, 70053 CANOSAOI PUGLIA-BA;Dr G Taverniti, 25043 BRENO-BS;Dr D Tedeschi, Div Chir, Osp Civ, PORDENONE;Prof P Tenchini, Prim la Div Chir, Ist Ospedal, MANTUA;Prof E Tendella, Dir Semeiotica Chir, TRIESTE;Prof O Terranova, Prim Div Chir Geriatr, Osp Civ, PADUA; Dr T Teodori, 00018 PALOMBARASABINA-ROMA;Dr R Tessari, 41012 CARPI-MO;Prof G Tiberio, Rep Chir 3a, Osp Gen Reg, BRESCIA;Dr F Tomaselli, 03012 ANAGNI-FR;Dr A Tomassini, Prim Rep Ostet Ginecol, Osp Circolo, TRADATE;Prof P Tombolini, 24040 ZINGONIA--BG;Prof A Travaglini, Div la Chir, Osp Gen Reg, UD1NE; Dr A Tremiterra, Prim Pronto Socc, Osp Umberto I, FROSINONE; Prof C Tremolada, Prim Rep Cbir la, Osp Riun, VENICE; Dr R Trotti, Rep Chir, Osp Civ, ALBENGA;Dr A Tuveri, 09170 ORISTANO;Dr P Vancini, Prim Div Urol, Osp Civ, BUSSOLENGO;Dr R Vasile, 89048 SIDERNOMARINA-RC;Prof C Vassallo, Prim Rep Chir, Osp Civ, STRADELLA;Prof P Ventrice, Prim Rep Urol, Osp Civ, VIBOVALENTIA;Dr T Verrienti, 73039 TRICASE--LE; Dr E de Vincentiis, 80131 NAPOLI;Prof A Vio, Prim Div Chir Gen, Osp Morgagni, FORLI; Prof D Zappavigna, 00165 ROMA; Dr D Zinzi, 81025 MARCIANISE-CE. A c k n o w l e d g m e n t T h e a u t h o r s gratefully acknowle d g e t h e s u p p o r t of R o u s s e l P h a r m a S.p.A. (Viale G r a n Sasso 18, 20131 Milan), H o e c h s t Italia S.p.A. (Via M . U . T r a i a n o 18, 20149 M i l a n ) and t h e c o o p e r a t i o n o f all p a r t i c i p a t i n g surgeons. REFERENCES 1. Periti P, Mazzei T, Costantini A, et al. Comparative pharmacokinetic evaluation of ceftriaxone and cefotaxime in coincidence for short-term antimicrobial prophylaxis in surgery. Chemoterapia 1984; 3: 305-9. 2. White RL, Nightingale CH, Quintiliani P, Whitaker KF, Jones RF 3d, Tripp WH. Serum and tissue concentrations of cefoxitin
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THE AMERICAN JOURNAL OF SURGERY
and cefotaxime in women undergoing hysterectomy. Drugs 1988; 35 (Suppl 2): 72-7. 3. Botto H, Richard F, Mathieu F, Perreau AM, Carney M. Short-term prophylaxis with cefotaxime in prostatic surgery. J Antimicrob Chemother 1984; 14 (Suppl B): 231-5. 4. Prokocimer P, Quazza M, Gibert C, et al. Short-term prophylac-
tic antibiotics in patients undergoing prostatectomy: report of a double-blind randomized trial with 2 intravenous doses of cefotaxime. J Urol 1986; 135: 60-4. 5. E1 Mufti MB, Glessa A. Single-dose clavulanate-potentiated amoxycillin versus three-dose cefotaxime in the prevention of wound infection following elective cholecystectomy: J Int Med Res 1988; 16: 92-7. 6. McDonald PJ, Sanders T, Higgins G, et al. Antibiotic prophylaxis in hysterectomy--cefotaxime compared to ampicillin-tinidazole. J Antimicrob Chemother 1984; 14 (Suppl B): 223-30. 7. Periti P, Mazzei T, Lamanna S, Mini E. Single-dose ceftriaxone versus multi-dose cefotaxime as short-term antimicrobial prophylaxis in urologic surgery. Preliminary results of a multicenter prospective randomized study. Chemoterapia 1984; 3: 295-8. 8. Periti P, Mazzei T, Orlandini F, Mini E. Comparison of the antimicrobial prophylactic efficacy of cefotaxime and cephazolin in obstetric and gynaecological surgery. A randomised multicentre study. Drugs 1988; 35 (Suppl 2): 133-8. 9. Roy S, Wilkins J. Single-dose cefotaxime versus 3 to 5 dose cefoxitin for prophylaxis of vaginal or abdominal hysterectomy. J Antimicrob Chemother 1984; 14 (Suppl B): 217-21. 10. Ridley PD, Sagar S. Cephalosporin prophylaxis in abdominal surgery. Br J Clin Pract 1988; 42: 337-42. 1 1. Guyot L. Prophylactic use of cefotaxime in biliary surgery. A prospective multicentre comparison of two dosage regimens. Drugs 1988; 35 (Suppl 2): 158-60. 12. Garcia-Rodriguez JA, Puig-LaCalle J, Arnau C, Porta M, Vallv6 C. Antibiotic prophylaxis with cefotaxime in gastroduodenal and biliary surgery. Am J Surg 1989; 158: 428-32. 13. Privitera G, Auxilia F, Castaldi S, Ortisi G, Pagano A. Epidemiologia e terapia delle infezioni in ambiente chirurgico. (Abstr.) 93rd National Congress (Florence, Oct. 1991), Italian Society of Surgery. 14. Sykes D, Basu PK. Prophylactic use of cefotaxime in elective biliary surgery. J Antimicrob Chemother 1984; 14: 237-9. 15. Di Palo S, Ferrari G, Castoldi R, et al. Effectiveness of antibiotic prophylaxis according to the nutritional status in patients undergoing contaminated procedures. Ital J of Surg Sci 1988; 18: 223-6. 16. Childs SJ, Kosola JW. Update of safety of cefotaxime. Clin Ther 1982; (Suppl A): 97-111.
VOLUME 164 NO. 4A (SUPPL)
OCTOBER 1992
![[Antibiotic prophylaxis in urologic surgery].](/assets/img/hold.png)
