Effect of outpatient antibiotics for urinary tract infections on antimicrobial resistance among commensal Enterobacteriaceae: a multinational prospective cohort study

Stewardson, Andrew J.; Vervoort, J.J.M.; Adriaenssens, Niels; Coenen, Samuel; Godycki-Cwirko, Maciek; Kowalczyk, Anna; Huttner, Benedikt; Lammens, Christine; Malhotra-Kumar, Surbhi; Goossens, Herman; Harbarth, Stéphan Juergen

doi:10.1016/j.cmi.2017.12.026

Cited by 59 publications

(51 citation statements)

References 35 publications

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“…22 These emphasised the lower rates of 'collateral damage' on gastrointestinal flora. [23][24] It remains to be seen if resistance rates increase as a consequence of this recommendation and the subsequent rise in nitrofurantoin prescribing. The true incidence of major hepatic and pulmonary toxicity is unclear, but this appears to be more common with long-term use in the elderly.…”

Section: Efficacy and Safetymentioning

confidence: 99%

Nitrofurantoin and fosfomycin for resistant urinary tract infections: old drugs for emerging problems

Gardiner¹,

Stewardson²,

Abbott³

et al. 2019

Aust Prescr

118

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Uncomplicated urinary tract infection is one of the most common indications for antibiotic use in the community. However, the Gram-negative organisms that can cause the infection are becoming more resistant to antibiotics. Many multidrug resistant organisms retain susceptibility to two old antibiotics, nitrofurantoin and fosfomycin. Advantages over newer drugs include their high urinary concentrations and minimal toxicity. Fosfomycin is a potential treatment option for patients with uncomplicated urinary tract infection due to resistant organisms. Nitrofurantoin may be more effective and can be used for urinary infections in pregnant women. Nitrofurantoin Nitrofurantoin has been available since 1953, and in Australia since the 1970s. Its exact mechanism of action is not well understood and presumably multifactorial. Nitrofurantoin requires reduction by bacterial enzymes producing 'highly reactive electrophilic' metabolites. These then inhibit protein synthesis by interfering with bacterial ribosomal proteins. 11 Nitrofurantoin has 80% oral bioavailability, and approximately 25% is excreted unchanged in the urine, with only a small portion reaching the colon. 12 Like fosfomycin, therapeutic concentrations are only reached in the urinary tract, 13 so the clinical use of nitrofurantoin is limited to the treatment of uncomplicated urinary tract infection in women. Administration with food results in higher urinary concentrations and fewer gastrointestinal adverse effects. Antimicrobial activity Nitrofurantoin is active against common causes of urinary tract infection including E. coli, Citrobacter and Enterococcus. Klebsiella and Enterobacter are less reliably susceptible. Serratia, Acinetobacter, Morganella, Proteus and Pseudomonas are usually resistant. 14 Overall, resistance to nitrofurantoin is uncommon and many multidrug resistant organisms retain susceptibility. 15-17 Australian data are limited, but studies suggest resistance rates in E. coli of 1-2%. 4,6

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Section: Efficacy and Safetymentioning

confidence: 99%

Nitrofurantoin and fosfomycin for resistant urinary tract infections: old drugs for emerging problems

Gardiner¹,

Stewardson²,

Abbott³

et al. 2019

Aust Prescr

118

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“…The exclusion of fluoroquinolones from routine treatment in outpatient therapy and searching for alternatives should be considered. The application of fluoroquinolones is becoming increasingly questionable and the limitation of their use is promoted by many scientists [7,[9][10][11][12]48,49]. In turn, ciprofloxacin induced cross-resistance to the smallest number of antibiotics in comparison to others.…”

Section: Antibiotics Induce Different Antibiotic Susceptibility Changesmentioning

confidence: 99%

“…Nowadays they are not only seen as E. coli isolated from urine, but a specialized pathotype with specific mechanisms of intracellular pathogenicity, which allow for colonization of the urinary tract, avoidance of host defenses and causing damage to the uroepithelium [3][4][5][6]. In addition, a high spread of antibiotic resistance is observed within these pathotypes [7][8][9][10][11][12]. They owe this high capacity to genetic modulate, own pathogenicity and drug resistance [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Ciprofloxacin, amoxicillin, and aminoglycosides stimulate genetic and phenotypic changes in uropathogenic Escherichia coli strains

et al. 2019

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Antibiotic therapy and its consequences in bacterial and human aspects are widely investigated. Despite this, the emergence of new multidrug resistant bacteria is still a current problem. The scope of our work included the observation of changes among uropathogenic Escherichia coli strains after the treatment with a subinhibitory concentration of different antibiotics. The sensitive strains with or without virulence factors were incubated with amoxicillin, ciprofloxacin, gentamycin, or tobramycin. After each passage, the E. coli derivatives were compared to their wild types based on their susceptibility profiles, virulence genes, biofilm formations and the fingerprint profiles of PCR products amplified with using the (N)(6)(CGG)(4) primer. It turned out that antibiotics caused significant changes in the repertoire of bacterial virulence and biofilm formation, corresponding to acquired cross-resistance. The genomic changes among the studied bacteria were reflected in the changed profiles of the CGG-PCR products. In conclusion, the inappropriate application of antibiotics may cause a rapid rise of Multidrug Resistant (MDR) strains and give bacteria a chance to modulate their own pathogenicity. This phenomenon has been easily observed among uropathogenic E. coli strains and it is one of the main reasons for recurrent infections of the urinary tract.

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“…Namely, they are associated with an increased risk of Closridioides di cile associated diarrhea and probably more so than most other antibiotics [22]; they can cause QT prolongation that may lead to arrhythmias; and their use is associated with tendinopathies, peripheral neuropathy, and rupture of aortic aneurysms [22]. Treatment with uoroquinolones quickly leads to colonization with resistant pathogens in the treated patients [18,23], and increases the risk of uoroquinolones resistance in certain geographic areas even in the absence of personal antibiotic use [24].…”

Section: Discussionmentioning

confidence: 99%

Pathogens Isolated in Respiratory Tract Samples of Recently Hospitalized Patients: Implications for Primary Care Physicians

Henig

Benaim

Neuberger

2020

Preprint

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Background. Little is known about the etiology of community-acquired lower respiratory tract infections (CA-LRTI), and treatment is largely empirical. We aimed to provide clinicians with microbiologic data of the more severe cases, i.e. those that result in hospital admission. Methods. A retrospective observational cohort study was conducted at a tertiary care hospital in Haifa, Israel. Consecutive respiratory tract samples obtained from admitted patients older than 12 years between 2014 and 2020 were included. Pathogen distribution and drug susceptibility were described, and factors associated with 14 day mortality rates were analyzed using a multivariable logistic regression with a stepwise model reduction. Results. A total of 1,395; 2,212; and 2,760 samples were included in the community-acquired, healthcare-associated and hospital-acquired LRTI groups, respectively. Gram negative bacteria were the most common bacteria isolated. Streptococcus pneumoniae was over represented in patients admitted to the intensive care unit (ICU) with CA-LRTI and healthcare-associated LRTI (accounting for 20% and 10.1% of patients admitted to the ICU versus 12.6% and 6.4% of patients in the entire cohort, p < 0.001). Streptococcus pneumoniae was susceptible to penicillin in around 50% of cases; to erythromycin in 65% of cases; and to fluoroquinolones and 3rd generation cephalosporins in more than 95% of cases. Twenty-five percent of other typical community-acquired pathogens (Hemophillus influenza, Moraxella spp., and Bordatella spp.) were resistant to ampicillin. Susceptibility of Gram negative bacteria to penicillins with and without a β-lactamase inhibitor and to second generation cephalosporins was lower than 50%. In the multivariable analysis, factors that were associated with increased mortality in the entire cohort were: age, admission to an ICU or surgical department, healthcare-associated or hospital-acquired infections, and infections with gram negative bacteria, Staphylococcus aureus, and Stenotrophomonas or Acinetobacter baummannii. Conclusions. Our data shows that gram negative bacteria are common causative agents among elderly patients with multiple comorbidities. Streptococcus pneumoniae and other typical community acquired pathogens are proportionally more common in younger patients, although most absolute cases occur in elderly patients. The susceptibility pattern of these community pathogens suggests that for high-risk patients the choice of effective oral antibiotic agents in the community is limited.

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Effect of outpatient antibiotics for urinary tract infections on antimicrobial resistance among commensal Enterobacteriaceae: a multinational prospective cohort study

Abstract: These findings support avoidance of fluoroquinolones for first-line UTI therapy in primary care, and suggest potential for interventions that interrupt household circulation of resistant Enterobacteriaceae.

Cited by 59 publications

References 35 publications

Nitrofurantoin and fosfomycin for resistant urinary tract infections: old drugs for emerging problems

Nitrofurantoin and fosfomycin for resistant urinary tract infections: old drugs for emerging problems

Ciprofloxacin, amoxicillin, and aminoglycosides stimulate genetic and phenotypic changes in uropathogenic Escherichia coli strains

Pathogens Isolated in Respiratory Tract Samples of Recently Hospitalized Patients: Implications for Primary Care Physicians

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