scholarly journals Emergence of Antibiotic Resistance during Therapy for Infections Caused by Enterobacteriaceae Producing AmpC β-Lactamase: Implications for Antibiotic Use

2007 ◽  
Vol 52 (3) ◽  
pp. 995-1000 ◽  
Author(s):  
Sang-Ho Choi ◽  
Jung Eun Lee ◽  
Su Jin Park ◽  
Seong-Ho Choi ◽  
Sang-Oh Lee ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Antimicrobial Therapy ◽  
Antimicrobial Agents ◽  
Medical Center ◽  
Antibiotic Use ◽  
Significance Level ◽  
Risk Of Mortality ◽  
Asan Medical ◽  
Bile Duct Invasion ◽  
Emergence Of Resistance

ABSTRACT Enterobacter spp., Serratia marcescens, Citrobacter freundii, and Morganella morganii are characterized by chromosomally encoded AmpC β-lactamases and possess the ability to develop resistance upon exposure to broad-spectrum cephalosporins. To determine the incidences of the emergence of resistance during antimicrobial therapy for infections caused by these organisms and the effect of the emergence of resistance on patient outcomes, all patients who were admitted to the Asan Medical Center (Seoul, Republic of Korea) from January 2005 to June 2006 and whose clinical specimens yielded Enterobacter spp., S. marcescens, C. freundii, or M. morganii were monitored prospectively. The main end point was the emergence of resistance during antimicrobial therapy. A total of 732 patients with infections were included for analysis. The overall incidence of the emergence of antimicrobial resistance during antimicrobial therapy was 1.9% (14/732). Resistance to broad-spectrum cephalosporins, cefepime, extended-spectrum penicillin, carbapenem, fluoroquinolones, and aminoglycosides emerged during treatment in 5.0% (11/218), 0% (0/20), 2.0% (2/100), 0% (0/226), 0% (0/153), and 1.1% (1/89) of patients, respectively. The emergence of resistance to broad-spectrum cephalosporins occurred more often in Enterobacter spp. (8.3%, 10/121) than in C. freundii (2.6%, 1/39), S. marcescens (0%, 0/37), or M. morganii (0%, 0/21). Biliary tract infection associated with malignant bile duct invasion was significantly associated with the emergence of resistance to broad-spectrum cephalosporins (P = 0.024 at a significance level of 0.042, by use of the Bonferroni correction). Only 1 of the 14 patients whose isolates developed resistance during antimicrobial therapy died. The emergence of resistance was more frequently associated with broad-spectrum cephalosporins than with the other antimicrobial agents tested, especially in Enterobacter spp. However, the emergence of resistance was associated with a low risk of mortality.

scholarly journals 1305. Application of Standard Antibiotic Use Criteria to Evaluate Inpatient Antibiotic Use

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S399-S399
Author(s):  
Maureen Campion ◽  
Emily Dionne ◽  
Elizabeth Radigan ◽  
Gail Scully ◽  
Moamen Al Zoubi ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Average Length ◽  
Medical Center ◽  
Pharmacy Practice ◽  
Antibiotic Use ◽  
Antifungal Prophylaxis ◽  
Prescribing Practices ◽  
Icu Patients ◽  
Inappropriate Use ◽  
Days Of Therapy

Abstract Background It is estimated that 30–50% of antimicrobial agents prescribed inpatient are not optimal. Historically, antimicrobial evaluation has been based primarily upon expert opinion of ID trained individuals. Spivak and colleagues proposed standard terminology and definitions to assess antimicrobial prescribing practices. At UMass Memorial Medical Center we utilized Spivak’s criteria to measure antimicrobial use within point prevalence studies (PPS) and assessed the ability of Spivak’s criteria to provide consistent results between different evaluators. Methods A PPS was conducted in September 2017 (SEPT) by infectious disease (ID) attendings and ID trained pharmacists. A follow-up PPS was completed in November 2017 (NOV) by a pharmacy practice resident (PGY-1) and first year ID fellow. Patients were included if they were prescribed antibiotics at the time of review, greater than 18 years of age, and admitted to an inpatient unit. Patients only receiving antiretroviral therapy or antifungal prophylaxis were excluded from the study. Antibiotics, indications, days of therapy, and appropriateness or reason for inappropriateness, as defined by Spivak’s criteria, were collected. Results Four hundred five patients in SEPT and 475 patients in NOV were reviewed. Baseline characteristics between SEPT and NOV, including sex, age, average length of hospital stay (LOS) at time of review were similar between groups, (SEPT vs. NOV: male sex: 53.2% vs. 51.1%; age: 60.4 vs. 61.7; LOS:8.55 vs. 8.36 days). Number of antibiotics per patient was different between PPS (SEPT 1.69 vs. NOV 1.28). For non-intensive care unit (ICU) patients, 64.9% of use was considered appropriate in SEPT vs. 69.3% in NOV. The top reasons for inappropriate use in non-ICU patients in both PPS were no indication and excess length of therapy. Within the ICU, 89.4% of use was considered appropriate in SEPT, with 75% of use considered appropriate in NOV. The top reason for inappropriate use in ICU patients in both PPS was overly broad therapy. Conclusion Application of standard antibiotic evaluation criteria can assist healthcare professionals with different levels of ID training to assess antibiotic use in non-ICU patients. Further evaluation should be considered for critically ill patients. Disclosures All authors: No reported disclosures.

Changes in the Incidences of Multidrug-Resistant and Extensively Drug-Resistant Organisms Isolated in a Military Medical Center

2010 ◽  
Vol 31 (7) ◽  
pp. 728-732 ◽  
Author(s):  
Edward F. Keen ◽  
Clinton K. Murray ◽  
Brian J. Robinson ◽  
Duane R. Hospenthal ◽  
Edgie-Mark A. Co ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
San Antonio ◽  
Medical Center ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Military Healthcare ◽  
Level I ◽  
Combat Casualties ◽  
The Military ◽  
Over Time

Background.Multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa have emerged as the causes of nosocomial infections in critically ill patients.Objective.To characterize the incidence of these MDR bacteria over time in the military healthcare system, comparing isolates recovered from overseas combat casualties with isolates recovered from local military and civilian patients.Methods.Retrospective electronic records review of culture and/or susceptibility testing results of patients admitted to a military level I trauma center in San Antonio, Texas, during the period from January 2001 through December 2008. Multidrug resistance was defined as the first isolated organism resistant to 3 or more classes of antimicrobial agents.Results.Over time, the percentage of MDR A. baumannii isolates increased from 4% to 55%, whereas the percentage of MDR P. aeruginosa isolates increased from 2% to 8%. Respiratory tract specimens had a higher percentage of MDR A. baumannii isolates (49%), compared with specimens obtained from blood (30%), wound sites (24%), or urine (19%). No difference in the percentages of MDR P. aeruginosa isolates was observed with regard to source of specimen. The percentage of MDR A. baumannii isolates recovered was higher among patients who had been deployed overseas (52%) than among local patients (20%). When isolates recovered from patients in the burn intensive care unit (53% of MDR A. baumannii isolates) were removed from analysis, the percentage of MDR A. baumannii isolates decreased from 38% to 30% while the percentage of MDR P. aeruginosa isolates remained unaffected.Conclusion.The percentage of MDR A. baumannii isolates increased in this facility among combat casualties and among local patients, which indicates nosocomial transmission; however, there was no significant increase in the percentage of MDR P. aeruginosa isolates. Isolated changes in the MDR pathogens within a facility can occur. Possible interventions to limit the spread of these organisms could include implementing aggressive infection control practices, controlling antibiotic use, and using active culture surveillance.

scholarly journals Association of Antibiotic Use with the Resistance Epidemiology of Pseudomonas aeruginosa in a Hospital Setting: A Four-Year Retrospective Time Series Analysis

2021 ◽  
Vol 89 (1) ◽  
pp. 13
Author(s):  
Rania Kousovista ◽  
Christos Athanasiou ◽  
Konstantinos Liaskonis ◽  
Olga Ivopoulou ◽  
Vangelis Karalis
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Broad Spectrum ◽  
Antimicrobial Agents ◽  
Transfer Functions ◽  
Moving Average ◽  
Hospital Setting ◽  
Antibiotic Use ◽  
Positive Correlations ◽  
Resistance Rates ◽  
Hospital Acquired

Background: Even though, Pseudomonas aeruginosa is a common cause of hospital-acquired infections, treatment is challenging because of decreasing rates of susceptibility to many broad-spectrum antibiotics. Methods: Consumption data of eight broad spectrum antimicrobial agents and resistance rates of P. aeruginosa were collected for 48 consecutive months. Autoregressive integrated moving average (ARIMA) and transfer functions models were used to develop relationships between antibiotic use and resistance. Results: Positive correlations between P. aeruginosa resistance and uses of ciprofloxacin (p < 0.001), meropenem (p < 0.001), and cefepime (p = 0.005) were identified. Transfer function models showed the quantified effect of each of these antibiotics on resistance. Regarding levofloxacin, ceftazidime, piperacillin/tazobactam and imipenem, no significant relationships were found. For ceftazidime and levofloxacin, this was probably due to their low consumption, while for imipenem the reason can possibly be ascribed to the already high established P. aeruginosa resistance in the hospital. Conclusion: In the hospital setting, the effect of antimicrobial agents’ consumption on the susceptibility epidemiology of P. aeruginosa differs significantly for each one of them. In this study, the role of precedent use of meropenem, cefepime and ciprofloxacin was quantified in the development of P. aeruginosa resistance.

scholarly journals Antibiotics in General Surgical Practice

JMS SKIMS ◽  
2018 ◽  
Vol 21 (1) ◽  
pp. 54-60
Author(s):  
Javid Ahmad Bhat ◽  
Ajaz Ahmad Malik ◽  
Nadiem Nazir Bhat
Keyword(s):  
Antifungal Therapy ◽  
Broad Spectrum ◽  
Antimicrobial Therapy ◽  
Antimicrobial Agents ◽  
Postoperative Mortality ◽  
Source Control ◽  
Individual Risk ◽  
Apache Ii Score ◽  
Short Period ◽  
Risk Patients

Introduction: Worldwide antibiotic prescription in surgical practices are inappropriate quite often, reasons being inappropriate indication, inappropriate antibiotic prophylaxis, continuation of empiric therapy despite negative cultures in a stable patient, and a lack of awareness of susceptibility patterns of common pathogens. Extended-spectrum b-lactamase, Carbapenemase resistant and multidrug-resistant strains of organisms causing intrabdominal infections, have developed. The occurrence of MRSA surgical site infection (SSI) has a significant impact on clinical and economic outcomes, notably an increase in postoperative mortality. Opportunities: There is an array of web of factors which affect the occurrence of SSI and antibiotics should not be answer or replacement to any of those factors. Narrow spectrum antibiotic active against the most probable pathogen to be encountered during operation, for a short period of time in adequate doses should be utilized. Broad-spectrum antimicrobial agents don’t result in lower rates of postoperative SSI compared to narrower spectrum. Elective laparoscopic cholecystectomy, parotidectomy, chest tube insertion and other clean procedures don’t warrant use of prophylaxis. For most patients who have had their wounds opened and adequately drained, antibiotic therapy is unnecessary. Antibiotics should be discontinued at time of incision closure (exceptions include implant-based breast reconstruction, joint arthroplasty, and cardiac procedures and liver transplantation. Hospital-specific antibiograms are important to guide the usage of diverse antibiotic agents to decrease resistance among pathogens. In intrabdominal infections source control is still integral and most important to the treatment of most patients. Routine use of antimicrobial therapy is not appropriate for all patients with intra-abdominal infections e.g. Patients with uncomplicated diverticulitis. In uncomplicated IAIs, when the focus of infection is treated effectively, the administration of antibiotics is unnecessary beyond prophylaxis e.g. Acute unperforated appendicitis removed surgically. In case of intraabdominal infections selection of empirical antimicrobial therapy depends on various factors which include probable contaminating pathogen/s, individual risk assessment and possibility of resistant pathogens. Higher risk patients are those, with severe sepsis/septic shock, elevated APACHE II score (>10), multiple medical comorbidities, problematic or delayed source control. The possibility of resistant pathogens is low in community acquired infections (CAI) in contrast to healthcare or hospital-associated infection (HAI). In Lower risk patients with community-acquired IAI, narrower-spectrum therapy ( coli, Bacteroides) is recommended and there is no need for anti-enterococcal or antifungal therapy. In Higher risk patients with community-acquired IAI, broader-spectrum therapy is recommended with selective use of anti-enterococcal and antifungal therapy. In Patients with healthcare/hospital-associated IAI, broader-spectrum therapy is recommended with additional agents for resistant pathogens. Do not use clindamycin as an anti-anaerobic agent in combination regimens for the empiric treatment in adults and children unless metronidazole cannot be used. Duration of antimicrobial therapy can be significantly shortened to 4-7 days under most of the circumstances. Routine addition of an aminoglycoside to other agents having broad spectrum gram negative coverage provides no additional benefit in intrabdominal infections. Conclusion: Antibiotics are a treasure but not unlimited. Appropriate use is the need of the hour to save our present and future generations from the menace of antimicrobial resistance. JMS 2018;21(1):54-60  

scholarly journals Cranberry-Derived Proanthocyanidins Potentiate β-Lactam Antibiotics Against Resistant Bacteria

2021 ◽  
Author(s):  
Mathias Gallique ◽  
Kuan Wei ◽  
Vimal B. Maisuria ◽  
Mira Okshevsky ◽  
Geoffrey McKay ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Antimicrobial Agents ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
E Coli ◽  
New Generation ◽  
Future Work ◽  
Emergence Of Resistance

The emergence and spread of extended-spectrum β-lactamases (ESBLs), metallo-β-lactamases (MBLs) or variant low affinity penicillin-binding proteins (PBPs) pose a major threat to our ability to treat bacterial infection using β-lactam antibiotics. Although combinations of β-lactamase inhibitors with β-lactam agents have been clinically successful, there are no MBL inhibitors in current therapeutic use. Furthermore, recent clinical use of new generation cephalosporins targeting PBP2a, an altered PBP, has led to the emergence of resistance to these antimicrobial agents. Previous work shows that natural polyphenols such as cranberry-extracted proanthocyanidins (cPAC) can potentiate non-β-lactam antibiotics against Gram-negative bacteria. This study extends beyond previous work by investigating the in vitro effect of cPAC in overcoming ESBL-, MBL- and PBP2a-mediated β-lactam resistance. The results show that cPAC exhibit variable potentiation of different β-lactams against β-lactam resistant Enterobacteriaceae clinical isolates as well as ESBL- and MBL-producing E. coli. We also discovered that cPAC have broad-spectrum inhibitory properties in vitro on the activity of different classes of β-lactamases, including CTX-M3 ESBL and IMP-1 MBL. Furthermore, we observe that cPAC selectively potentiate oxacillin and carbenicillin against methicillin-resistant but not methicillin-sensitive Staphylococci, suggesting that cPAC also interfere with PBP2a-mediated resistance. This study motivates the need for future work to identify the most bioactive compounds in cPAC and to evaluate their antibiotic potentiating efficacy in vivo. IMPORTANCE Emergence of β-lactam resistant Enterobacteriaceae and Staphylococci compromised the efficiency of β-lactams-based therapy. By acquisition of ESBLs, MBLs or PBPs, it is highly likely that bacteria become completely resistant to the most efficient β-lactam agents in the near future. In this study, we described a natural extract rich in proanthocyanidins which exerts adjuvant properties by interfering with two different resistance mechanisms. By their broad-spectrum inhibitory ability, cranberry-extracted proanthocyanidins could have the potential to enhance effectiveness of existing β-lactam agents.

An Interventional Program to Improve Antibiotic Use

2003 ◽  
Vol 37 (5) ◽  
pp. 646-651 ◽  
Author(s):  
Cynthia L Feucht ◽  
Louis B Rice
Keyword(s):  
Clinical Pharmacist ◽  
Antimicrobial Agents ◽  
Medical Center ◽  
Antibiotic Use ◽  
Resistant Bacteria ◽  
Prescribing Practices ◽  
Gram Negative ◽  
Inappropriate Use ◽  
Multidisciplinary Program ◽  
Empiric Antibiotic

BACKGROUND: Large volume and often inappropriate use of specific antimicrobial agents increase selective pressure for emergence of resistant bacteria and place strain on the pharmacy budget. OBJECTIVE: To initiate a multidisciplinary program designed to align intravenous vancomycin and fluoroquinolone prescribing practices with guidelines for appropriate use of these agents. METHODS: A multidisciplinary, prospective interventional program was implemented to encourage early discontinuation of inappropriate vancomycin and fluoroquinolone therapy and decrease inappropriate duplicative gram-negative coverage using fluoroquinolones. A computerized review was performed for patients receiving intravenous vancomycin and fluoroquinolones for 1998 in a Veterans Affairs Medical Center. In June 1999, guidelines were disseminated and an interventional program was initiated, with a monthly conference for medical residents regarding antimicrobial resistance and local hospital practices. Concurrently, a prospective review of new orders was assessed by the clinical pharmacist and interventions performed when inappropriate use occurred. RESULTS: The interventional program was successful in reducing unnecessary duplicative gram-negative coverage with intravenous fluoroquinolones by 26% (p < 0.001) from 1998 to 2001. Overall, a 43% reduction in the number of courses of intravenous fluoroquinolones was seen during these 4 years. Courses lasting >5 days were reduced by 22% (p < 0.001). Vancomycin prescriptions deemed inappropriate that were administered >5 days were reduced by 16% (p < 0.001) during the same time period. The interventions performed by the clinical pharmacist were deemed successful, with a 76% acceptance rate by providers. CONCLUSIONS: Education of physicians through monthly conferences and personal interventions resulted in an increase in appropriate empiric antibiotic use, a decrease in the duration of inappropriate use, and a decrease in duplicate gram-negative coverage.

scholarly journals Three Decades of β-Lactamase Inhibitors

2010 ◽  
Vol 23 (1) ◽  
pp. 160-201 ◽  
Author(s):  
Sarah M. Drawz ◽  
Robert A. Bonomo
Keyword(s):  
Clinical Practice ◽  
Antimicrobial Agents ◽  
Selective Pressure ◽  
Antibiotic Use ◽  
Mechanisms Of Action ◽  
Single Class ◽  
Life Saving ◽  
Catalytic Mechanisms ◽  
Emergence Of Resistance ◽  
Lactamase Inhibitor

SUMMARYSince the introduction of penicillin, β-lactam antibiotics have been the antimicrobial agents of choice. Unfortunately, the efficacy of these life-saving antibiotics is significantly threatened by bacterial β-lactamases. β-Lactamases are now responsible for resistance to penicillins, extended-spectrum cephalosporins, monobactams, and carbapenems. In order to overcome β-lactamase-mediated resistance, β-lactamase inhibitors (clavulanate, sulbactam, and tazobactam) were introduced into clinical practice. These inhibitors greatly enhance the efficacy of their partner β-lactams (amoxicillin, ampicillin, piperacillin, and ticarcillin) in the treatment of seriousEnterobacteriaceaeand penicillin-resistant staphylococcal infections. However, selective pressure from excess antibiotic use accelerated the emergence of resistance to β-lactam-β-lactamase inhibitor combinations. Furthermore, the prevalence of clinically relevant β-lactamases from other classes that are resistant to inhibition is rapidly increasing. There is an urgent need for effective inhibitors that can restore the activity of β-lactams. Here, we review the catalytic mechanisms of each β-lactamase class. We then discuss approaches for circumventing β-lactamase-mediated resistance, including properties and characteristics of mechanism-based inactivators. We next highlight the mechanisms of action and salient clinical and microbiological features of β-lactamase inhibitors. We also emphasize their therapeutic applications. We close by focusing on novel compounds and the chemical features of these agents that may contribute to a “second generation” of inhibitors. The goal for the next 3 decades will be to design inhibitors that will be effective for more than a single class of β-lactamases.

scholarly journals Antimicrobial Susceptibilities of Geographically Diverse Clinical Human Isolates of Leptospira

2008 ◽  
Vol 52 (8) ◽  
pp. 2750-2754 ◽  
Author(s):  
Roseanne A. Ressner ◽  
Matthew E. Griffith ◽  
Miriam L. Beckius ◽  
Guillermo Pimentel ◽  
R. Scott Miller ◽  
...  
Keyword(s):  
Antimicrobial Therapy ◽  
Antimicrobial Agents ◽  
Limit Of Detection ◽  
Medical Center ◽  
Penicillin G ◽  
Geographic Variability ◽  
Broth Microdilution ◽  
Randomized Controlled ◽  
The World ◽  
Susceptibility Patterns

ABSTRACT Although antimicrobial therapy of leptospirosis has been studied in a few randomized controlled clinical studies, those studies were limited to specific regions of the world and few have characterized infecting strains. A broth microdilution technique for the assessment of antibiotic susceptibility has been developed at Brooke Army Medical Center. In the present study, we assessed the susceptibilities of 13 Leptospira isolates (including recent clinical isolates) from Egypt, Thailand, Nicaragua, and Hawaii to 13 antimicrobial agents. Ampicillin, cefepime, azithromycin, and clarithromycin were found to have MICs below the lower limit of detection (0.016 μg/ml). Cefotaxime, ceftriaxone, imipenem-cilastatin, penicillin G, moxifloxacin, ciprofloxacin, and levofloxacin had MIC90s between 0.030 and 0.125 μg/ml. Doxycycline and tetracycline had the highest MIC90s: 2 and 4 μg/ml, respectively. Doxycycline and tetracycline were noted to have slightly higher MICs against isolates from Egypt than against strains from Thailand or Hawaii; otherwise, the susceptibility patterns were similar. There appears to be possible variability in susceptibility to some antimicrobial agents among strains, suggesting that more extensive testing to look for geographic variability should be pursued.

scholarly journals The impact of pricing and patent expiration on demand for pharmaceuticals: an examination of the use of broad-spectrum antimicrobials

2012 ◽  
Vol 8 (1) ◽  
pp. 7-20 ◽  
Author(s):  
Klaus Kaier
Keyword(s):  
Broad Spectrum ◽  
Antimicrobial Agents ◽  
Hospital Setting ◽  
Antibiotic Use ◽  
Patent Expiration ◽  
Price Elasticities ◽  
Time Series Approach ◽  
Outpatient Sector ◽  
Using Data ◽  
The Impact

AbstractThe aim of the analysis was to determine whether demand in Germany for specific antimicrobial agents is driven by prices that drop considerably when generic substitutes become available. A time-series approach was therefore carried out to explore price elasticities of demand for two different classes of broad-spectrum antimicrobials (fluoroquinolones and cephalosporins) using data on ambulatory antibiotics prescribed on the German statutory health insurance scheme and data on in-hospital antibiotic use in a German teaching hospital. In short, we attempted to explain demand for different antibiotics based on changes in price and hospital-wide morbidity. The data indicate that patent expiration is followed by substantial decreases in the price of antibiotics. In the outpatient sector, all antibiotics included in the analysis showed significant negative own-price elasticities of demand. However, in the hospital settings, significant own-price elasticities were only determined for some antibiotics, although price decreases were stronger than in the outpatient sector. We conclude that price dependence of demand for antimicrobials is present both in the ambulatory and the hospital setting. However, this is especially surprising in the hospital setting because price differences among the antibiotics observed are particularly small compared with the overall cost of hospitalisation.

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