Norfloxacin Prophylaxis Research Articles

Bacterial infections in cirrhosis: Epidemiological changes with invasive procedures and norfloxacin prophylaxis

The extensive use of invasive procedures and of long-term norfloxacin prophylaxis in the management of cirrhotic patients may have influenced the epidemiology of bacterial infections in cirrhosis. We conducted a prospective evaluation of all bacterial infections diagnosed in patients with cirrhosis in a Liver Unit between April 1998 and April 2000. A total of 405 patients presented 572 bacterial infections in 507 admissions. Spontaneous bacterial peritonitis was the most frequent infection (138 cases). Gram-positive cocci were responsible for 53% of total bacterial infections in the study, being the main bacteria isolated in nosocomial infections (59%). Patients requiring treatment in an intensive care unit and those submitted to invasive procedures presented a higher rate of infections caused by gram-positive cocci (77% vs. 48%, P < .001 and 58% vs. 40%, P < .02, respectively). Fifty percent of culture-positive spontaneous bacterial peritonitis in patients on long-term norfloxacin administration (n = 93) and 16% in patients not receiving this therapy (n = 414) were caused by quinolone-resistant gram-negative bacilli, P = .01. The rate of culture-positive spontaneous bacterial peritonitis caused by trimethoprim-sulfamethoxazole–resistant gram-negative bacilli was also very high in patients on long-term norfloxacin administration (44% vs. 18%, P = .09). In conclusion, infections caused by gram-positive cocci have markedly increased in cirrhosis. This phenomenon may be related to the current high degree of instrumentation of cirrhotic patients. Quinolone-resistant spontaneous bacterial peritonitis constitutes an emergent problem in patients on long-term norfloxacin prophylaxis, with trimethoprim-sulfamethoxazole not being a valid alternative. (H EPATOLOGY 2002;35:140-148.)

Epidemiology of hospital-acquired infections in cirrhotic patients: effect of carriage of methicillin-resistant Staphylococcus aureus and influence of previous antibiotic therapy and norfloxacin prophylaxis.

We assessed the prevalence of carriage of methicillin-resistant Staphylococcus aureus (MRSA) in anterior nares and stools, and of third-generation cephalosporin resistant enterobacteriaceae and non-fermenting gram-negative bacilli (RE/RNF) in stools of 748 hospitalized long-stay cirrhotic patients. We also evaluated the consequences of carriage on the epidemiology of hospital-acquired spontaneous bacterial peritonitis, bacteraemia and urinary tract infection (UTI) in these patients. The prevalence of carriage of MRSA and RE/RNF was 16.7% and 14.7% respectively. Whereas RE/RNF carriage did not lead to an increased risk of infection due to RE/RNF, the overall risk of infections caused by MRSA was more than tenfold higher in MRSA carriers. MRSA and RE/RNF carriers had received prior antibiotic therapy to a greater extent than non-carriers (P < 0.001) and MRSA carriers had received prior norfloxacin prophylaxis to a greater extent than the two other groups (P < 0.02). The mortality rate during hospital stay was higher in MRSA and RE/RNF carriers than in non-carriers (P < 0.001). Pugh score (P < 0.0001), age (P < 0.0001), MRSA carriage (P = 0.0018) and bacteraemia (P = 0.0017) were associated independently with mortality. MRSA carriage in hospitalized cirrhotic patients leads to the emergence of infections due to this strain, mainly SBP and bacteraemia. Prior antibiotic therapy and norfloxacin prophylaxis increase the risk of carriage of MRSA.

Unsuspected infection is infrequent in asymptomatic outpatients with refractory ascites undergoing therapeutic paracentesis.

Large-volume paracentesis is a safe and effective means of treating patients with refractory ascites. However, there is limited information regarding the need for ascitic fluid studies in asymptomatic outpatients presenting for therapeutic paracentesis. The aim of this prospective study was to define the incidence and natural history of peritoneal fluid infection in asymptomatic outpatients undergoing therapeutic paracentesis. Over a 13-month period, 118 therapeutic paracenteses were performed in 29 outpatients with decompensated cirrhosis (Child-Pugh class B = 38%, C = 62%). After a brief medical history and physical examination, ascitic fluid cell count with differential and culture were obtained from all participating subjects. Seven (24%) of the subjects were receiving norfloxacin prophylaxis, accounting for antibiotic coverage during 40% of the procedures performed. The clinical course and outcome of study subjects during a mean follow-up of 137 days was reviewed. All 118 (100%) of the ascitic fluid samples demonstrated absolute neutrophil counts of <250/mm3 (mean = 6.5 +/- 22.5 pmn/mm3). Asymptomatic bacterascites was identified from three of the 118 (2.5%) fluid samples, but all of these subjects spontaneously recovered without treatment or sequelae. During follow-up, six episodes of symptomatic or hospital-associated peritoneal fluid infection were identified in study participants, emphasizing the importance of fluid studies in other clinical settings. Although further studies are needed, the routine culture of ascitic fluid in asymptomatic outpatients with refractory ascites requiring therapeutic paracentesis may not be necessary when there is a low index of suspicion for occult infection. In circumstances of clinical uncertainty, however, obtaining ascitic fluid cell counts with differential is recommended to insure patient safety.

Unsuspected infection is infrequent in asymptomatic outpatients with refractory ascites undergoing therapeutic paracentesis

OBJECTIVE: Large-volume paracentesis is a safe and effective means of treating patients with refractory ascites. However, there is limited information regarding the need for ascitic fluid studies in asymptomatic outpatients presenting for therapeutic paracentesis. The aim of this prospective study was to define the incidence and natural history of peritoneal fluid infection in asymptomatic outpatients undergoing therapeutic paracentesis. METHODS: Over a 13-month period, 118 therapeutic paracenteses were performed in 29 outpatients with decompensated cirrhosis (Child-Pugh class B = 38%, C = 62%). After a brief medical history and physical examination, ascitic fluid cell count with differential and culture were obtained from all participating subjects. Seven (24%) of the subjects were receiving norfloxacin prophylaxis, accounting for antibiotic coverage during 40% of the procedures performed. The clinical course and outcome of study subjects during a mean follow-up of 137 days was reviewed. RESULTS: All 118 (100%) of the ascitic fluid samples demonstrated absolute neutrophil counts of <250/mm 3 (mean = 6.5 ± 22.5 pmn/mm 3). Asymptomatic bacterascites was identified from three of the 118 (2.5%) fluid samples, but all of these subjects spontaneously recovered without treatment or sequelae. During follow-up, six episodes of symptomatic or hospital-associated peritoneal fluid infection were identified in study participants, emphasizing the importance of fluid studies in other clinical settings. CONCLUSIONS: Although further studies are needed, the routine culture of ascitic fluid in asymptomatic outpatients with refractory ascites requiring therapeutic paracentesis may not be necessary when there is a low index of suspicion for occult infection. In circumstances of clinical uncertainty, however, obtaining ascitic fluid cell counts with differential is recommended to insure patient safety.

Development of quinolone-resistant strains of Escherichia coli in stools of patients with cirrhosis undergoing norfloxacin prophylaxis: clinical consequences

Background/Aim: Norfloxacin prophylaxis decreases the incidence of bacterial infections in high-risk cirrhotic patients, but may promote the development of quinolone-resistant gram-negative bacteria in stools, and eventually lead to infections due to these bacteria. The aim of the study was to evaluate the prevalence of quinolone-resistant strains of E.coli in stools on admission, and the characteristics of any nosocomial infections. Methods: Eighty-three consecutively hospitalized cirrhotic patients were included in this prospective study. The presence of quinolone-resistant strains of E.coli in stools on admission, and the characteristics of any nosocomial infections were recorded. Results: Fourteen out of 83 patients (16.8%) showed quinolone-resistant E. coli in stools (Group I), and 69 did not (Group II). Thirteen out of 14 from Group I (92.8%) and 17/69 (24.6) from Group II had received primary or secondary prophylaxis with norfloxacin ( p<001). During hospitalization, 12/12 (100%) of patients from Group I and 25/66 (37.8%) of patients from Group II underwent norfloxacin prophylaxis. Three bacterial infections in patients from Group I, 3 from Group II patients receiving norfloxacin and 16 from Group II patients not receiving norfloxacin were recorded ( p<05). No infections due to quinolone-resistant E. coli were observed in patients colonized with these bacteria. Treatment with norfloxacin induced the development of quinolone-resistant E. coli in 6/14 (42.8%) patients in a mean time of 18.5±9.8 days. Conclusions: The development of quinolone-resistant strains of E. coli is significantly associated with previous administration of norfloxacin prophylaxis. However, in our series this fact is not associated with an increased incidence of quinolone-resistant E. coli or other gram-negative infections.

Effect of Discontinuing Prophylaxis with Norfloxacin in Patients with Hematologic Malignancies and Severe Neutropenia

The use of fluorinated quinolones for prophylaxis of infections in neutropenic cancer patients has led to a reduction of infections with gram-negative enteric bacilli, but there is concern about the emergence of antibiotic-resistant enterobacterial infections and a rise of gram-positive bacteremias. Due to these concerns, in mid-1995 the use of prophylactic norfloxacin was discontinued in our unit. In order to evaluate the impact of this measure on the infectious morbidity in our unit, 91 severe neutropenic episodes in 58 patients with hematologic malignancies who did not receive norfloxacin prophylaxis (NO group) were closely matched to 91 episodes in 60 patients who received norfloxacin prophylaxis (NORFLO group). There were no differences in the incidence of febrile neutropenia, fever of unknown origin or bacteremia during the first febrile episode. There was a trend for a higher rate of coagulase-negative staphylococcal bacteremia in the NORFLO group (5 vs. 11 cases in the NO and NORFLO groups, respectively, p = NS). Enterobacterial bloodstream infections were more frequent in the NO group (13 vs. 2 cases, respectively, p = 0.01), especially Escherichia coli (9 vs. 1 case, respectively, p = 0.01). Twelve of 13 enterobacterial isolates in the NO group were sensitive to the fluoroquinolones vs. 0/2 in the NORFLO group (p = 0.07). We conclude that the abrupt discontinuation of norfloxacin prophylaxis in our ward led to a rapid increase in the rate of fluoroquinolone-susceptible enterobacterial infections, with a scarce impact on infectious morbidity. This suggests that the selection of resistant flora in an inpatient ward by prophylactic antimicrobials may be reversible following the discontinuation of the prophylactic agent(s).

Cost-analysis of prophylactic antibiotics in spontaneous bacterial peritonitis

BACKGROUND & AIMS: Antibiotic prophylaxis has been shown to decrease the incidence of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and ascites. The aim of this study was to test whether antibiotic prophylaxis for SBP is cost-effective and to compare the costs associated with different patient groups and treatment strategies.METHODS: A cost-effectiveness analysis was performed using a Markov chain model. The costs incurred during 1-year treatment with prophylactic antibiotics vs. no prophylaxis in patients with cirrhosis and ascites were calculated. The incidence rates of primary and recurrent SBP and the mortality rate of SBP were obtained from the literature. Total direct costs of SBP treatment were determined from the wholesale price of drugs and from disbursements by the Health Care Financing Administration.RESULTS: Norfloxacin prophylaxis resulted in savings between $2216 and $8545 per patient per year, depending on the patient group studied. Trimethoprim-sulfamethoxazole prophylaxis resulted in savings between $2934 and $9251 per patient per year. The groups that benefited most from prophylaxis were patients with an ascitic fluid total protein concentration of < or = 1 g/dL and those with a previous history of SBP.CONCLUSIONS: The use of prophylactic antibiotics to decrease the incidence of SBP is a cost-saving strategy in patients with cirrhosis and ascites.(Gastroenterology 1997 Oct;113(4):1289-94)

An economic analysis of norfloxacin prophylaxis against spontaneous bacterial peritonitis

Background/Aims/Methods: Spontaneous bacterial peritonitis (SBP) is a frequent complication of advanced liver disease and in high-risk patients, it is associated with a mean (per episode) mortality of 29% and a mean 1-year mortality of 82%. The 1-year recurrence rate of SBP can be as high as 30–70%. Selective intestinal decontamination with antibiotic prophylaxis has been shown to significantly reduce the incidence of recurrent SBP. The aim of this study was to perform an economic analysis of norfloxacin prophylaxis to prevent SBP recurrence. Results: This analysis showed that nofloxacin prophylaxis in high-risk patients with cirrhosis resulted in USD 4632 savings per patient per year by avoiding SBP and its associated expense. A sensitivity analysis showed that the norfloxacin prophylaxis remained cost-saving, even if it resulted in only a modest reduction in the SBP recurrence rate. Conclusions: Selective gut decontamination with norfloxacin is not only efficacious in preventing SBP, but can also be cost-saving by avoiding the resource utilization associated with its treatment.

Spontaneous bacterial peritonitis in patients with cirrhosis undergoing selective intestinal decontamination: A retrospective study of 229 spontaneous bacterial peritonitis episodes

Background/Aims: Selective intestinal decontamination with norfloxacin is widely used to prevent spontaneous bacterial infections in cirrhosis. The study was performed to compared the spontaneous bacterial peritonitis occurring in patients with and without prophylactic norfloxacin. Methods: Two hundred and twenty-nine consecutive episodes of spontaneous bacterial peritonitis, (193 patients without (Group A) and 36 in patients with norfloxacin prophylaxis (Group B)), were retorspectively analyzed. In 100 episodes (86 and 14, respectively), the responsible organism was isolated in ascitic fluid. Results: Clinical and laboratory data at diagnosis were comparable in both groups. There were marked differences ( p<0.001) between group A and B in the frequency of peritonitis caused by gram-negative (67.4% vs. 14.3%) and gram-positive (30.2% vs. 78.6%) bacteria. There were three polymicrobial episodes. Bacteria resistant to cefotaxime and gram-negative bacilli resistant to quinolones were isolated in ascitic fluid in nine (seven in Group A and two in Group B) and three episodes (all in Group A), respectively. No differences in the course of infection and patient survival were observed between groups. Conclusions: Spontaneous bacterial peritonitis in patients with and without prophylaxis with norfloxacin are not different in clinical features, response to treatment and prognosis. Spontaneous bacterial peritonitis caused by gram-negative organisms resistant to quinolones is extremely uncommon in patients with cirrhosis receiving prophylatic norfloxacin.

Selective intestinal decontamination with norfloxacin reduces bacterial translocation in ascitic cirrhotic rats exposed to hemorrhagic shock.

Bacterial translocation (BT) can be involved in the pathogenesis of severe infections due to bacteria of enteric origin that complicates bleeding cirrhotic patients. To assess the effect of hemorrhagic shock (HS) on the incidence of BT and if selective intestinal decontamination (SID) reduces this incidence, we studied six groups of Sprague-Dawley rats: ascitic rats, ascitic rats exposed to HS with and without previous norfloxacin prophylaxis, healthy rats, and healthy shocked rats with and without previous norfloxacin prophylaxis. BT tended to be higher in ascitic rats with shock than without shock (69% vs. 41%, P = .15) and was significantly higher in healthy rats with than without shock (50 percent vs. 0 percent, P = .01). Norfloxacin significantly reduced translocation in ascitic shocked rats in comparison with nondecontaminated ascitic shocked rats (31 percent vs. 69 percent, P = .038). This effect was due mainly to a reduction of gram-negative BT (O percent vs. 37 percent, P = .008). In addition, norfloxacin prevented translocation in healthy shocked rats. Accordingly, aerobic gram-negative bacteria disappeared from fecal flora in all rats administered norfloxacin, except for Klebsiella species in one control rat. Cecal severe submucosal edema, chronic inflammatory infiltrate, and intestinal lymphangiectasia were significantly more frequent in ascitic rats than in control rats. Intestinal mucosal injury related with HS, particularly subepithelial cecal edema, was observed only in ascitic shocked rats. In conclusion, HS increases the incidence of BT both in ascitic cirrhotic and healthy rats. Norfloxacin reduces significantly the incidence of translocation after shock, especially in those cases caused by aerobic gram-negative bacilli.

Selective intestinal decontamination with norfloxacin reduces bacterial translocation in ascitic cirrhotic rats exposed to hemorrhagic shock

Bacterial translocation (BT) can be involved in the pathogenesis of severe infections due to bacteria of enteric origin that complicates bleeding cirrhotic patients. To assess the effect of hemorrhagic shock (HS) on the incidence of BT and if selective intestinal decontamination (SID) reduces this incidence, we studied six groups of Sprague-Dawley rats: ascitic rats, ascitic rats exposed to HS with and without previous norfloxacin prophylaxis, healthy rats, and healthy shocked rats with and without previous norfloxacin prophylaxis. BT tended to be higher in ascitic rats with shock than without shock (69% vs. 41%, P = .15) and was significantly higher in healthy rats with than without shock (50 percent vs. 0 percent, P = .01). Norfloxacin significantly reduced translocation in ascitic shocked rats in comparison with nondecontaminated ascitic shocked rats (31 percent vs. 69 percent, P = .038). This effect was due mainly to a reduction of gram-negative BT (O percent vs. 37 percent, P = .008). In addition, norfloxacin prevented translocation in healthy shocked rats. Accordingly, aerobic gram-negative bacteria disappeared from fecal flora in all rats administered norfloxacin, except for Klebsiella species in one control rat. Cecal severe submucosal edema, chronic inflammatory infiltrate, and intestinal lymphangiectasia were significantly more frequent in ascitic rats than in control rats. Intestinal mucosal injury related with HS, particularly subepithelial cecal edema, was observed only in ascitic shocked rats. In conclusion, HS increases the incidence of BT both in ascitic cirrhotic and healthy rats. Norfloxacin reduces significantly the incidence of translocation after shock, especially in those cases caused by aerobic gram-negative bacilli. (Hepatology 1996 Apr;23(4):781-7)

Is norfloxacin prophylaxis against SBP cost effective? An economic analysis: [formula omitted]. Division of GI/Hepatology, Scripss Clinic & Research Foundation, La Jolla, CA∗

Is norfloxacin prophylaxis against SBP cost effective? An economic analysis: [formula omitted]. Division of GI/Hepatology, Scripss Clinic & Research Foundation, La Jolla, CA∗

Norfloxacin as Prophylaxis Against Urethral Strictures following Transurethral Resection of the Prostate: An Open, Prospective, Randomized Study

An open, prospective, randomized study was performed to investigate the effect of norfloxacin prophylaxis on stricture formation and operative outcome after transurethral resection of the prostate. After resection, the 359 patients studied were randomly divided into 2 groups: 1) those given norfloxacin as prophylaxis for 15 days following removal of the catheter (norfloxacin group) and 2) those given no antimicrobial prophylaxis during the same period (control group). Of the patients 94 were excluded. At followup 6 to 12 months postoperatively, the number of strictures in the anterior urethra was 2 of 135 in the norfloxacin group and 22 of 130 in the control group (p <0.01). Strictures in the bladder neck developed in 3 of 135 and 4 of 130 patients, respectively (not significant). As a consequence of a lower stricture incidence in the anterior urethra in the norfloxacin group, fewer patients in that group were dissatisfied with the operative outcome. The results suggest that norfloxacin provides effective prophylaxis against stricture formation after transurethral resection of the prostate.

Norfloxacin prophylaxis for acute recurrent uncomplicated urinary tract infection in women

Long-term low dose antimicrobial prophylaxis is effective for the prevention of recurrent uncomplicated urinary infections in women. The fluoroquinolone antimicrobials, including norfloxacin, have an in vitro spectrum effective for most uropathogens, and generally achieve high concentrations in the urine. In addition, they are effective for eradication of aerobic Gram-negative flora from the gut. These features suggest these antimicrobials should be effective agents for antimicrobial prophylaxis for urinary infection. Only norfloxacin has been studied in clinical trials to date. In two of the three studies reported, norfloxacin was effective for prophylaxis compared to placebo. In the third study, it was as effective as nitrofurantoin macrocrystals. Infections which occurred during prophylaxis were with organisms resistant to norfloxacin, particularly Enterococcus faecalis and Pseudomonas aeruginosa. Norfloxacin is effective for the prevention of recurrent uncomplicated urinary infections in women. Further studies comparing it to standard regimens are required to identify its specific niche in the management of this common problem.

Norfloxacin: Its potential in clinical practice

The in vitro spectrum and potency of norfloxacin against both aerobic gram-negative and gram-positive bacteria, its limited activity against anaerobes, and the apparent difficulty organisms have in acquiring resistance to it, have provided a rationale for the clinical development of this oral fluoroquinolone antimicrobial agent. The clinical experience with norfloxacin as treatment for a variety of urinary tract infection syndromes, uncomplicated gonococcal infection, and diarrheal disease, and as prophylaxis of infection in neutropenic patients with cancer, is reviewed. Norfloxacin appears at least equivalent to standard regimens for the treatment of acute urinary tract infections; however, long-term studies are needed to define its role in the treatment of recurrent urinary infections. Initial studies of norfloxacin treatment of uncomplicated gonococcal infection and bacterial gastroenteritis are also promising, and in neutropenic patients, continuous norfloxacin prophylaxis has been shown to reduce the incidence of gram-negative infections. Further prospective evaluation is required to confirm these findings.