Proof‑of‑concept study to quantify changes in intestinal loads of KPC-producing Klebsiella pneumoniae in colonised patients following selective digestive decontamination with oral gentamicin. (September 2022)

• Record Type: Journal Article
• Authors: Pérez-Nadales, Elena; Natera, Alejandra M.; Recio-Rufíán, Manuel; Guzmán-Puche, Julia; Cano, Ángela; Frutos-Adame, Azahara; Castón, Juan José; Elías-López, Cristina; Romero-Saldaña, Manuel; López-Cerero, Lorena; Martínez-Martínez, Luis; Torre-Cisneros, Julián
• Is Part Of: Journal of global antimicrobial resistance. Volume 30(2022)
• Page Start: 16
• Page End: 22
• Publication Date: 2022-09
• Subjects: Intestinal colonisation -- Selective digestive decontamination -- Antimicrobial resistance -- KPC-producing Klebsiella pneumoniae -- Bacterial load; Drug resistance -- Periodicals; Drug resistance -- Periodicals; Drug resistance; Periodicals; 616.9041
• DOI: 10.1016/j.jgar.2022.04.010
• Languages: English
• ISSNs: 2213-7165

Abstract

Highlights: We developed and validated a qPCR method for quantitative determination of the extent of intestinal colonisation by KPC-producing Klebsiella pneumoniae ( KPC-Kp). This validated qPCR method detects 17% more positives for KPC-Kp and reduces ≥24 h the time required by a reference method based on standard culture. A rapid and persistent reduction of KPC-Kp intestinal load is observed in about 60% of patients within a month of selective digestive decolonisation with oral gentamicin; however, only 17% of patients reach persitent eradication at this time point. The death rate was significantly higher among patients with high baseline KPC-Kp intestinal loads. The validated qPCR method will help to strengthen public health efforts to monitor colonisation by carbapenemase-producing Klebsiella pneumoniae through rapid screening of KPC-producing Klebsiella spp. ABSTRACT: Objectives: To monitor quantitatively the extent of intestinal colonisation by KPC-producing Klebsiella pneumoniae (KPC-Kp) in colonised patients who receive selective digestive decontamination (SDD) with oral gentamicin. Methods: We developed a real-time quantitative PCR (qPCR) method for determination of the relative load of bla KPC (RLKPC ) within the gut microbiota. Clinical validation was performed using a culture method as the gold standard and receiver operating curve (ROC) analysis. Fifteen patients were observationally and prospectively followed for one year. Clinical, microbiological variables and rectal swab samples were collected at 0 (baseline), 14 and 30 days and monthly thereafter. Results: Clinical validation performed on 111 rectal swab samples demonstrated that the PCR method detected 17% more positives than the culture method. ROC curve analysis documented excellent agreement between both methods (area under the curve, 0.96; 95% confidence interval 0.93–0.99). The RLKPC decreased in 6/15 (40%) and 7/12 (58.3%) patients on days 14 and 30, respectively. Persistent eradication was observed in 2/12 (16.7%), 3/9 (33.3%), 4/8 (50%) and 7/8 (87.5%) patients at 1, 3, 6 and 12 months, respectively, with a median time of 150 days (range 30–270) to persistent eradication. Gentamicin-resistant KPC-Kp isolates were identified in 4/15 (26.7%) patients. The rates of infections (57.1% vs. 12.5%, P = 0.119) and deaths (71.4% vs. 0%, P = 0.007) were higher among patients with high baseline RLKPC . Conclusion: Following SDD, a rapid reduction on intestinal load is observed when the colonising KPC-Kp isolate is susceptible to gentamicin; however, persistent eradication at the end of SDD is low. Intestinal carriage of KPC-Kp persists after three months in about one third of patients.