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Oa3-comparative

THAI J GASTROENTEROL 2007
Vol. 8 No. 1
Ua-sukphanpranee B, Anantapanpong S Jan. - Apr. 2007
Comparative Study Between Norfloxacin and Ciprofloxacin in
Prophylaxis of Spontaneous Bacterial Peritonitis in
Cirrhotic Patients
This study was conduct prospective randomized study to compare efficacy of ciprofloxacin, 750 mg weekly, with norfloxacin, 400 mg daily, in prophylaxis of spontaneous bacterial peritonitis in cirrhotic patients. From March 2005 to Jan 2006, 25 patients were randomized by block of four to receive prophylaxis antibiotic with norfloxacin 400 mg daily (N group) or Ciprofloxacin 750 mg weekly (C group). Both groups will follow up as out- patients monthly for 6 months. There were no difference in baseline characteristic of both groups. Ascites fluid culture was positive 3/13 patients from norfloxacin group and 2/12 patients from ciprofloxacin group reported E.coli. Only 1/13 patient from ciprofloxacin group infected with Klebsiella pneumoniaei. No serious adverse reac- tion reported from both groups. We concluded that there were no differences prophylaxis between ciprofloxacin group and norfloxacin group.
Key words : SBP, peritonitis, ciprofloxacin, norfloxacin
[Thai J Gastroenterol 2007; 8(1): 19-22] less than 1.0 mg/dl and previous history of spontane- Cirrhosis is a frequent condition in internal medi- ous bacterial peritonitis. Antibiotic prophylaxis in gas- cine and likely to develop complications. Spontane- trointestinal hemorrhage patients has been shown to ous bacterial an important complication in these pa- decreased infection rate(3,4). Antibiotic prophylaxis in tients. Hospitalized patients had spontaneous bacte- low ascitic protein (<1.0 mg/dl) is also decreased the rial peritonitis range from 10-30%(1). Mortality rate risk for bacterial peritonitis when compared with pla- can be as high as 30% even early diagnosis and treat- cebo(6-9). One year recurrent bacterial peritonitis is as ment is done(2). Important risks for bacterial peritoni- high as 69% in patients who previously had bacterial tis are gastrointestinal bleeding, ascetic fluid protein peritonitis.(2) Antibiotic prophylaxis in these patients Address for Correspondence: Siriwat Anantapanpong, Gastrointestinal Unit, Rajvithi Hospital, Bangkok 10400, Thailand
* Fellowship in Gastroenterology Rajvithi Hospital ** Gastrointestinal Unit, Rajvithi Hospital, Bangkok, Thailand Comparative Study Between Norfloxacin and Ciprofloxacin in Prophylaxis of
Spontaneous Bacterial Peritonitis in Cirrhotic Patients
had the recurrent rate at 22% when compared with 68 four randomization to received prophylaxis antibiotic % in the placebo group(10). Moreover prophylaxis norfloxacin 400 mg daily (N group) or Ciprofloxacin antibiotic is found to be more cost-effectiveness than 750 mg weekly (C group). Both groups will follow up as out-patients monthly for 6 months. Baseline char- Prophylaxis antibiotic used in these studies was acteristic (age. sex, etiology of cirrhosis, CPT score quinolone compound group which had action against and complication of cirrhosis) was collect by the time gram negative bacilli. Gram negative bacilli are im- of enrollment. Clinical and laboratory was collected portant pathogen in spontaneous bacterial peritonitis.
at each visit and at the end of follow up. Patients who A study compared between norfloxacin 400 mg per had gastrointestinal hemorrhage during follow up time day with placebo. Recurrent rate in placebo group was will switch antibiotic to norfloxacin 400 mg twice daily 9% and no recurrent infection in norfloxacin group8.
or others appropriated antibiotic and switched to pro- The main problem after prophylaxis antibiotic was bac- tocol drug when they was discharge from hospital. Any terial resistance to drug used. Ciprofloxacin adminis- patient who had sign or symptom of infection will in- tration weekly also had decreased recurrent infection.
vestigate further including abdominal paracentesis if Ciprofloxacin 750 mg weekly for 6 months had recur- they had suspected of SBP. Patients who had infection rent infection 4% compared with 22% in placebo others than SBP will treat with appropriate antibiotic group.(9) Interestingly, group which received cipro- and switch to protocol drug after completed treatment.
floxacin weekly none was shown to had bacterial Those who had spontaneous bacterial peritonitis be- resistant to antibiotic used(9) while in study of fore end of follow up will be define as recurrence bac- norfloxacin as prophylaxis antibiotic found resistance terial peritonitis. End point was those who had recur- organism may be as high as 69%(12).
rence bacterial peritonitis. Those who died from other Ciprofloxacin in role of antibiotic prophylaxis can than SBP, who losses follow up and who cannot toler- be used as weekly dose can make convenient and can ate drug treatment will not include in this study.
increase compliance for patients. And in past studydid not found resistance strain to ciprofloxacin. So we conduct prospective randomized study to compare ef- Sample sized was calculated on basis of previous ficacy of ciprofloxacin, 750 mg weekly, with study that prophylaxis with norfloxacin had no infec- norfloxacin, 400 mg daily, in prophylaxis of spontane- tion and with ciprofloxacin had infection rate 9 % . On ous bacterial peritonitis.
the basis of α = 0.05, β = 0.02, Pc (norfloxacin group)= 0% and Pt (ciprofloxacin group) = 9%. A sample METHOD AND MATERIAL
size was 66 per each group. However due to shortageof collective time. Sample groups in this study was not reached estimated sample sized. And data will be Prospective randomized comparative trial in cir- calculated as preliminary study. We used chi-square rhotic patient risk which have risk factor for spontane- to compare between nominal parameter and t-test to ous bacterial infection in Rajvithi hospital. High risk compare numeric parameter. SPSS version 13 program patients were patients who have previous history of was used to calculate all data.
spontaneous bacterial peritonitis (SBP) and/or whohave ascetic protein less than 1.0 mg/dl. SBP was di- agnose by ascitic PMN more than 250/mm3 with clini-cal, laboratory and no radiologic evidence of second- Due to limited time of studied, we collected data ary bacterial peritonitis or any abdominal pathology from only 25 patients that far from calculated 132 pa- such tuberculosis, peritonitis, hemorrhage or carcino- tients and made this study had less power to detect any matosis. Exclusion criteria was Renal failure (Serum significant between 2 experimental groups. Any way creatinine >1.5 mg/dl), presence of hepatocellular car- this studied may give a clue for further larger studied cinoma and drug allergy to quinolone group.
in the future. From March 2005 to Jan 2006 at Depart-ment of Internal medicine, 41 cirrhotic patients were screening to enroll in this study. There were 12 pa- Patient was allocate to study group by block of tients excluded from this study. 6 patients had renal THAI J GASTROENTEROL 2007
Vol. 8 No. 1
Ua-sukphanpranee B, Anantapanpong S Jan. - Apr. 2007
failure (serum creatinine >2.0 mg/dl), 3 patients had ciprofloxacin group (25 %, 3/12). 2 patient s had SBP hepatocellular carinoma 2 patients had severe gas- at 3 months period which 1 patient occurred with he- trointestinal bleeding and subsequently dead. And 1 patic encephalopathy and 1 patient infection occurred patient had severe sepsis. In remaining 29 patients 4 after gastrointestinal hemorrhage. One patient had SBP cases was unable to follow up as study protocol. So after follow up for 4 months period. No one in only 25 patients was randomized to study. 13 patients norfloxacin group has SBP (0 %, 0/13). When com- were randomized to receive norfloxacin 400 mg daily pare in 2 groups there were no significant in SBP event and 12 patients were randomized to receive cipro- in 2 groups (p = 0.09). Organism culture from blood, floxacin 750 mg weekly as prophylaxis antibiotic. And urine or ascitic fluid from 3 infected patients was nega- 10 baseline parameter define as age, sex, etiology of tive. So we don't have data whether organism resisted cirrhosis (viral or non viral), Gastrointestinal bleed- to prophylaxis antibiotic or not. All SBP patients were ing. Hepatic encephalopathy, serum total billirubin treated by third generation cephalosporin and have (mg/dl), Serum albumin (mg/dl), ascetic protein (mg/ clinical response to cephalosporin drugs. In 3 SBP Pa- dl), Child-Pugh-Turcot score and positive ascetic fluid tient there are only one who have low ascetic fluid pro- culture of both group was collected during time of en- tein with previous SBP while the others not.
rollment. Baseline characteristic of both groups wasnot difference as show in Table 1 Ascitic fluid culture was positive in 6 patients.
3 patients from norfloxacin group have E. coli. 2 In general practice secondary prophylaxis with patient from ciprofloxacin group was also infected with daily norfloxacin was widely accepted(13). Cipro- E. coli. Only one patient from ciprofloxacin group in- floxacin was also used as prophylaxis antibiotic and fected with Klebsiella pneumoniaei. All of those or- had good result in both daily(14) and weekly dose(9). In ganisms were sensitive to third generation cepha- this study there were 3 SBP in ciprofloxacin group and losporin given. About drug safety and adverse reac- none in norfloxacin group. There are no differences tion to prophylaxis drug given. There are reports only between both groups. There was previous study using minor adverse effects report from norfloxacin group 3 long acting quinolone rufloxacin compare with patients had nausea and 2 had headache. All of those norfloxacin in preventing recurrent SBP(15). Rufloxacin were symptomatic treatment and symptom disappeared had more probability of having SBP at 3 months pe- after follow up. There was no adverse reaction reported riod than norfloxacin (9%versus 3%, p = 0.03) but not from ciprofloxacin group. No serious adverse reac- at 1 years (36 % versus 26 %, p = 0.16). Moreover in tion report from both groups.
patients who receive rufloxacin 2 in 12 patients hadrecurrent peritonitis from quinolone-resistant bacterial Spontaneous bacterial peritonitis after prophy-
(one E. coli and one K. pneumoniae). And rufloxacin had 7 Enterobacteriacae infections while norfloxacin There was 3 SBP and all of 3 infections occur in group not. When compared only Enterobacteriacae Table 1 Baseline characteristic of both treatment groups
Chr viral infection Hepatic encephalopathy 2.56 SD 0.572.65 SD 0.15 Positive ascitic fluid culture Comparative Study Between Norfloxacin and Ciprofloxacin in Prophylaxis of
Spontaneous Bacterial Peritonitis in Cirrhotic Patients
strain, norfloxacin group had more efficacy in prevent 5. Runyon B. Low-protein concentration ascitic fluid is predis- recurrent SBP than ciprofloxacin (0% vs 22%,p = 0.01).
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6. Soriano G, Guarner C, Teixido M, et al. Selective intestinal was not alternative to norfloxacin in preventing of re- decontamination prevent spontaneous bacterial peritonitis.
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any difference in recurrent SBP during 6 months fol- 7. Singh N, Gayowski T, Yu VL, et al. Trimethoprim-sulfa- low up period. All recurrence in ours study was oc- methoxazole for the prevention of spontaneous bacterial peri- curred within 4 month. Two third of infection occurred tonitis in cirrhosis: a randomized trial. Ann Intern Med 1995; in 3 months. The reason for this may be small popula- 8. Grange JD, Roulot D, Pelletier G, et al. Norfloxacin primary tion groups in this study that gave less power to detect prophylaxis of bacterial infection in cirrhotic patients with any significant. If larger population was study may be ascite: a double blind randomized trial. J Hepatol 1998; 29: the result will be the same as previous study. In our study no organism was culture from recurrent SBP. So 9. Rolanchon A, Cordier L, Bacq Y, et al. Ciprofloxacin and we can't evaluate whether organism resisted to pro- long-term prevention of spontaneous bacterial peritonitis: re- phylaxis quinolone compound or not. There was in- sult of aprospective controlled trial. Hepatology 1995; 22:1171-4.
crease incidence of gram positive bacteria culture from 10. Gines P, Rimola A, Planas R, et al. Norfloxacin prevents spon- SBP patients(16). Recurrent SBP in our study may be taneous bacterial peritonitis recurrence in cirrhosis: result of cause by gram positive organism that not sensitive to a double-blind, placebo-controlled trial. Hepatology 1990; quinolone compound used. From this data it would wiser not to used ciprofloxacin as prophylaxis antibi- 11. Younossi ZM, McHutchison JG, Ganiats T. An economic otic routinely until its benefit are clearified. Recent analysis of norfloxacin prophylaxis against spontaneous bac-terial peritonitis. J Hepatol 1997; 27: 295.
study was shown that medical prophylaxis of variceal 12. Novella M, Sola R, Soriano G, et al. Continuous versus inpa- bleeding by beta blocker reduced incidences of bacte- tient prophylaxis of the first episode of spontaneous bacterial rial peritonitis(17). May be combine both variceal bleed- peritonitis with norfloxacin. Hepatology 1999; 29: 1064-9.
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