Intravesical Gentamicin Treatment for Recurrent Urinary Tract Infections Caused by Multidrug Resistant Bacteria.

PURPOSE: Antimicrobial resistance leads to complications in the management of recurrent urinary tract infections. In some patients with recurrent urinary tract infections who have limited treatment options intravenous therapy with reserve antibiotics is often required. In this study we assessed the effectiveness, safety and feasibility of prophylactic treatment with intravesical gentamicin in patients with refractory recurrent urinary tract infections caused by multidrug resistant microorganisms. MATERIALS AND METHODS: This was a prospective trial of 63 adults with recurrent urinary tract infections caused by multidrug resistant pathogens who were enrolled at 1 academic and 1 general hospital in The Netherlands between 2014 and 2017. The intervention was overnight intravesical instillations of gentamicin for 6 months. The primary outcome was the recurrence rate of urinary tract infections compared to that in the preceding 6 months. Secondary objectives included assessment of the safety of intravesical gentamicin instillation and its influence on the development of antibiotic resistance in uropathogens. RESULTS: The mean number of urinary tract infections was reduced from 4.8 to 1.0 during intravesical treatment. The resistance rate of the uropathogens decreased from 78% to 23%. No systemic absorption or clinically relevant side effects were observed. CONCLUSIONS: Intravesical gentamicin instillation reduced the number of urinary tract infection episodes and the degree of antimicrobial resistance.

Recurrent respiratory tract infections (RRTI) in the elderly: A late onset mild immunodeficiency?

Elderly with late-onset recurrent respiratory tract infections (RRTI) often have specific anti-polysaccharide antibody deficiency (SPAD). We hypothesized that late-onset RRTI is caused by mild immunodeficiencies, such as SPAD, that remain hidden through adult life. We analyzed seventeen elderly RRTI patients and matched controls. We determined lymphocyte subsets, expression of BAFF receptors, serum immunoglobulins, complement pathways, Pneumovax-23 vaccination response and genetic variations in BAFFR and MBL2. Twelve patients (71%) and ten controls (59%) had SPAD. IgA was lower in patients than in controls, but other parameters did not differ. However, a high percentage of both patients (53%) and controls (65%) were MBL deficient, much more than in the general population. Often, MBL2 secretor genotypes did not match functional deficiency, suggesting that functional MBL deficiency can be an acquired condition. In conclusion, we found SPAD and MBL deficiency in many elderly, and conjecture that at least the latter arises with age.

Using local clinical and microbiological data to develop an institution specific carbapenem-sparing strategy in sepsis: a nested case-control study.

Background: From a stewardship perspective it is recommended that antibiotic guidelines are adjusted to the local setting, accounting for the local epidemiology of pathogens. In many settings the prevalence of Gram-negative pathogens with resistance to empiric sepsis therapy is increasing. How and when to escalate standard sepsis therapy to a reserve antimicrobial agent, is a recurrent dilemma. The study objective was to develop decision strategies for empiric sepsis therapy based on local microbiological and clinical data, and estimate the number needed to treat with a carbapenem to avoid mismatch of empiric therapy in one patient (NNTC). Methods: We performed a nested case control study in patients (> 18 years) with Gram-negative bacteremia in 2013-2016. Cases were defined as patients with Gram-negative bacteremia with in vitro resistance to the combination 2nd generation cephalosporin AND aminoglycoside (C-2GC + AG). Control patients had Gram-negative bacteremia with in vitro susceptibility to cefuroxime AND/OR gentamicin, 1:2 ratio. Univariate and multivariable analysis was performed for demographic and clinical predictors of resistance. The adequacy rates of empiric therapy and the NNTC were estimated for different strategies. Results: The cohort consisted of 486 episodes of Gram-negative bacteremia in 450 patients. Median age was 66 years (IQR 56-74). In vitro resistance to C-2GC + AG was present in 44 patients (8.8%). Independent predictors for resistance to empiric sepsis therapy were hematologic malignancy (adjusted OR 4.09, 95%CI 1.43-11.62, p < 0.01), previously cultured drug resistant pathogen (adjusted OR 3.72. 95%CI 1.72-8.03, p < 0.01) and antibiotic therapy during the preceding 2 months (adjusted OR 12.5 4.08-38.48, p < 0.01). With risk-based strategies, an adequacy rate of empiric therapy of 95.2-99.3% could be achieved. Compared to treating all patients with a carbapenem, the NNTC could be reduced by 82.8% (95%CI 78.5-87.5%) using the targeted approaches. Conclusions: A risk-based approach in empiric sepsis therapy has the potential to better target the use of reserve antimicrobial agents aimed at multi-resistant Gram-negative pathogens. A structured evaluation of the expected antimicrobial consumption and antibiotic adequacy rates is essential to be able to weigh the costs and benefits of potential antibiotic strategies and select the most appropriate approach.