Risk of emergence of Pseudomonas aeruginosa resistance to β-lactam antibiotics in intensive care units

Georges, Bernard; Conil, Jean‐Marie; Dubouix, Anne; Archambaud, M.; Bonnet, É.; Saivin, Sylvie; Lauwers‐Cancès, Valérie; Cristini, C.; Cougot, P.; Decun, J. F.; Mathe, Olivier; Chabanon, G.; Marty, N.; Seguin, Thierry; Houin, Georges

doi:10.1097/01.ccm.0000215517.51187.ca

Cited by 40 publications

(29 citation statements)

References 33 publications

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“…The exposed data show that patients received in our ICU are predominantly male, which is consistent with other studies. [12][13][14][15][16] According to Ciampone, 17 men have a higher ICU admission frequency because they use primary and secondary health care services less. In the population studied by Gomes, 18 the absence of men seeking health services can be explained by fear of discovering a severe illness, shame to expose their body to a health professional, the absence of exclusive units for the treatment of men's health and a limited availability of public services.…”

Section: Discussionmentioning

confidence: 99%

Epidemiological profile of ICU patients at Faculdade de Medicina de Marília

El-Fakhouri

Carrasco

Araújo

et al. 2016

Rev. Assoc. Med. Bras.

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Objective: To characterize the epidemiological profile of the hospitalized population in the ICU of Hospital das Clínicas de Marília (Famema). Method: A retrospective, descriptive and quantitative study. Data regarding patients admitted to the ICU Famema was obtained from the Technical Information Center (Núcleo Técnico de Informações, NTI, Famema). For data analysis, we used the distribution of absolute and relative frequencies with simple statistical treatment. Results: 2,022 ICU admissions were recorded from June 2010 to July 2012 with 1,936 being coded according to the ICD-10. The epidemiological profile comprised mostly males (57.91%), predominantly seniors ≥ 60 years (48.89%), at an average age of 56.64 years (±19.18), with limited formal education (63.3% complete primary school), mostly white (77.10%), Catholic (75.12%), from the city of Marília, state of São Paulo, Brazil (53.81%). The average occupancy rate was 94.42%. The predominant cause of morbidity was diseases of the circulatory system with 494 admissions (25.5%), followed by traumas and external causes with 446 admissions (23.03%) and neoplasms with 213 admissions (11.00%). The average stay was 8.09 days (±10.73). The longest average stay was due to skin and subcutaneous tissue diseases, with average stay of 12.77 days (±17.07). There were 471 deaths (24.32%), mainly caused by diseases of the circulatory system (30.99%). The age group with the highest mortality was the range from 70 to 79 years with 102 deaths (21.65%). Conclusion:The ICU Famema presents an epidemiological profile similar to other intensive care units in Brazil and worldwide, despite the few studies available in the literature. Thus, we feel in tune with the treatment of critical care patients.

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Section: Discussionmentioning

confidence: 99%

Epidemiological profile of ICU patients at Faculdade de Medicina de Marília

El-Fakhouri

Carrasco

Araújo

et al. 2016

Rev. Assoc. Med. Bras.

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“…Over the past decade, the prevalence of ciprofloxacin-resistant (Cip R ) PA strains has increased 3-fold in parallel to the trend of prescribing this antibiotic class 7 . Upwards of 30% of clinical PA strains are multidrug-resistant, and some are resistant to all available antibiotics 5, 8–10 . In addition, PA strains have an arsenal of virulence factors, including a type III secretion system (TTSS) that induces cytotoxicity and expression of ExoU or ExoS effector proteins which are virulence factors that influence disease severity by phagocyte evasion during acute infections 11 .…”

Section: Introductionmentioning

confidence: 99%

Microbicidal effects of α- and θ-defensins against antibiotic-resistantStaphylococcus aureusandPseudomonas aeruginosa

et al. 2013

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Antibiotic-resistant bacterial pathogens threaten public health. Because many anti-biotics target specific bacterial enzymes or reactions, corresponding genes may mutate under selection and lead to antibiotic resistance. Accordingly, antimicrobials that selectively target overall microbial cell integrity may offer alternative approaches to therapeutic design. Naturally occurring mammalian α- and θ-defensins are potent, non-toxic microbicides that may be useful for treating infections by antibiotic-resistant pathogens, because certain defensin peptides disrupt bacterial but not mammalian cell membranes. To test this concept, clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), including vancomycin heteroresistant strains, and ciprofloxacin-resistant Pseudomonas aeruginosa (CipR-PA) were tested for sensitivity to α-defensins Crp-4, RMAD-4, and HNPs 1–3, and to RTD-1, a macaque θ-defensin-1. In vitro, 3 µM Crp-4, RMAD-4, and RTD-1 reduced MRSA cell survival by 99%, regardless of vancomycin susceptibility. For PA clinical isolates that differ in fluoroquinolone resistance and virulence phenotype, peptide efficacy was independent of strain ciprofloxacin resistance, site of isolation, or virulence factor expression. Thus, Crp-4, RMAD-4, and RTD-1 are effective in vitro antimicrobials against clinical isolates of MRSA and CipR-PA, perhaps providing templates for development of α- and θ-defensin-based microbicides against antibiotic resistant or virulent infectious agents.

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“…[1][2][3] Increases in multidrugresistant gram-negative bacteria are diminishing treatment options for infections that were previously cured with an armamentarium of antimicrobials, [4][5][6] and there are no new prospects in the pharmaceutical pipeline in the foreseeable future. 7 Aminoglycosides (AGs) are commonly used to manage these infections in ICU patients as part of a combination regimen in an attempt to increase the chance of initial effective therapy.…”

Section: Introductionmentioning

confidence: 99%

Suboptimal Aminoglycoside Dosing in Critically Ill Patients

Rea¹,

Capitano²,

Bies³

et al. 2008

Therapeutic Drug Monitoring

128

104

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Maximal aminoglycoside (AG) killing requires that the ratio of peak serum concentrations (Cmax) to the minimum inhibitory concentration (MIC) of the pathogen exceeds by > or =10. This has been shown to hasten resolution of infection in the general patient population. It was postulated that critically ill patients, likely to have larger intravascular volumes, are underdosed. The primary aim was to determine Cmax to MIC target attainment rate in medical intensive care unit (MICU) patients. A retrospective review of MICU patients who received at least 1 intravenous dose and serum concentration of either gentamicin or tobramycin was performed. A population pharmacokinetic model was developed, and MIC distributions for AG were used in determining the Cmax/MIC and in calculating the probability of attaining the pharmacodynamic (PD) target. One hundred two unique patients with 211 AG concentrations were analyzed to determine population pharmacokinetic parameters. Mean maximum clearance (CL) was 3.14L/h (95% confidence interval: 1.26-4.54 L/h), and mean volume of distribution (V) was 53 L (95% confidence interval: 38-66.8 L/h). Glomerular filtration rate and standardized body weight were identified as significant covariates for clearance in the final model. Standardized body weight also significantly affected V. There was only a 20% and 40% probability that patients receiving 7 mg/kg of gentamicin and tobramycin, respectively, will achieve PD target over the range of MIC distributions. Based on these data, the majority of critically ill patients would not be predicted to achieve the PD target under current dosing regimens. This may be a result of intensive care unit patients having a larger volume of distribution than reported in the literature. Future recommendations for treating gram-negative infections in the MICU population include using initial doses of 7 mg/kg of either gentamicin or tobramycin, measuring Cmax after the first dose, and determining MIC for the pathogen(s) with adjustment of subsequent doses to achieve the PD target.

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Risk of emergence of Pseudomonas aeruginosa resistance to β-lactam antibiotics in intensive care units

Abstract: Our results show that there is a high risk of the emergence of drug resistance during treatment with cefotaxime, imipenem, and piperacillin-tazobactam. This has to be taken into account in the therapeutic choice and in the patient's surveillance.

Cited by 40 publications

References 33 publications

Epidemiological profile of ICU patients at Faculdade de Medicina de Marília

Epidemiological profile of ICU patients at Faculdade de Medicina de Marília

Microbicidal effects of α- and θ-defensins against antibiotic-resistantStaphylococcus aureusandPseudomonas aeruginosa

Suboptimal Aminoglycoside Dosing in Critically Ill Patients

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