Quinolone and Multidrug Resistance Predicts Failure of Antibiotic Prophylaxis of Spontaneous Bacterial Peritonitis

Abstract

Background The efficacy of antibiotic prophylaxis to prevent spontaneous bacterial peritonitis (SBP) in patients colonized with multidrug-resistant organisms (MDROs) is unknown. We evaluated the effectiveness of fluoroquinolone-based SBP prophylaxis in an era and area of frequent antibiotic resistance. Methods This is a prospective observational study in patients with liver cirrhosis and an indication for fluoroquinolone-based prophylaxis of SBP. Patients were recruited and followed in a large German tertiary reference center with comprehensive microbiological and clinical monitoring performed at baseline and after 30, 60, 90, and 180 days of prophylaxis. Results Overall, 77 patients received antibiotic prophylaxis for an average of 93 days. Baseline prevalence of colonization with MDROs was high (N = 39, 50.6%). At least one de novo MDRO was detected in 27 patients (35.1%) during antibiotic prophylaxis; 33 patients (42.9%) developed secondary infections, including 14 cases (17.9%) of infections with MDROs, and 13 cases (16.9%) of de novo/recurrent SBP. Thirty patients (39.0%) died during follow-up. Significantly higher risks of SBP development during antibiotic prophylaxis were observed for patients with versus without any apparent MDROs (P = .009), vancomycin-resistant enterococci (P = .008), multidrug-resistant gram-negative bacteria (P = .016), or quinolone-resistant gram-negative bacteria (QR-GNB) (P = .015). In competing risk analysis, QR-GNB were independently associated with prophylaxis failure (hazard ratio, 3.39; P = .045) and infections with QR-GNB were independently associated with death before SBP (subdistribution hazard risk, 6.47; P = .034). Conclusions Antibiotic prophylaxis of SBP appears to be less efficient in patients with known MDROs. Regular MDRO screening seems to be useful to tailor treatment of secondary infections and re-evaluate antibiotic prophylaxis in case of selection of quinolone resistance.

Efficacy of Norfloxacin Prophylaxis to Prevent Spontaneous Bacterial Peritonitis: A Systematic Review and Meta-Analysis

“…Most recently, the CANONIC study group reported a high and increasing prevalence of MDROs in culture-positive infections in patients with decompensated cirrhosis all over Europe ( 15 ). We have recently shown in a prospective cohort study that the effectiveness of SBP prophylaxis might be critically reduced in an environment of highly prevalent MDROs ( 16 ).…”

Stool and sputum microbiome during quinolone prophylaxis of spontaneous bacterial peritonitis: an exploratory study

“…Currently, there is an ongoing debate as to whether to extend the indication for antibiotic prophylaxis in cirrhosis: so far, it has been recommended for patients with ascites at high risk for SBP (primary prophylaxis) or with prior SBP (secondary prophylaxis) [ 5 , 6 ]. We observed higher risk of prophylaxis failure in patients with known status of multidrug-resistant bacteria (MDRO) and a recent meta-analysis reported a reduced efficacy of quinolone prophylaxis to prevent SBP over the last decades [ 8 , 23 ], while others have observed an alarming increase of MDRO in patients with cirrhosis over time [ 24 , 25 ]. Yet, Moreau et al [ 7 ] observed in a recently published, large randomized controlled trial significantly reduced overall infection rates in cirrhotic patients in general and a better overall survival in those with low ascites protein content.…”

“…Primary or secondary antibiotic prophylaxis with quinolones was started at baseline in all patients at the time of study inclusion, either with norfloxacin 400 mg once daily or ciprofloxacin 500 mg once daily; the choice between both agents was made at the treating physicians’ discretion. Patients were part of the observational study on MDRO prevalence and occurrence of MDRO under SBP prophylaxis; details on the study protocol and clinical outcome are reported elsewhere [ 8 ]. In the present sub-analysis of this study, patients were included if they were willing to provide serial stool samples.…”

“…[ 7 ] Although the primary endpoint was not met (improvement of overall survival), they observed reduced infection rates, especially with regards to gram-negative bacteria, and an improved survival in a subgroup of patients with low ascites protein. Yet, the effectiveness of quinolone prophylaxis has been questioned as to whether all patients might benefit, especially those with known multidrug-resistant bacterial colonization or infection [ 8 ].…”

<p>Clinical Efficacy and Cost-Effectiveness of β-Lactam/β-Lactamase Inhibitor Combinations and Carbapenems in Liver Cirrhosis Patients with Gram-Negative Bacteria Bloodstream Infection</p>

“…Therefore, these recommendations also emphasize that empirical antibiotic strategies need to be tailored according to local microbiological epidemiology. Notably, a previous study showed that the use of carbapenems was the only strong independent predictor for the emergence of MDR bacteria, including carbapenem-resistant MDR bacteria, 14 which represents a substantial global health and economic threat, and simultaneously increase the risk of death and the length of stay in patients with BSI. 15 Hence, it should be noted that carbapenems-sparing therapy options are urgently necessary to reduce the continuing prevalence of MDR bacteria 16 and consequent economic threat.…”