- Predictors of insufficient peak amikacin concentration in critically ill patients on extracorporeal membrane oxygenation. [Journal Article]
- CCCrit Care 2018 Aug 19; 22(1):199
- CONCLUSIONS: ECMO-treated patients were under-dosed for amikacin in one third of cases. Increasing the dose to 35 mg/kg of body weight in low-BMI patients and those with positive 24-h fluid balance on ECMO to reach adequate targeted concentrations should be investigated.
- Bacteriuria and asymptomatic infection in chronic patients with indwelling urinary catheter: The incidence of ESBL bacteria. [Journal Article]
- MMedicine (Baltimore) 2018; 97(33):e11796
- Urinary tract infections due to the presence of a urinary catheter represent a real problem for patients who have to carry such an invasive device for a long time.Our aim was to identify the suscepti...
Urinary tract infections due to the presence of a urinary catheter represent a real problem for patients who have to carry such an invasive device for a long time.Our aim was to identify the susceptibility of extended spectrum beta lactamases (ESBL) versus non-ESBL bacteria to antibiotics in urinary tract infections in patients who are chronic carriers of urinary catheters.The retrospective study included a period of 5 years, a total of 405 patients who are chronic carriers of urinary catheters, admitted to rehabilitation and palliative care units.Escherichia coli (E coli) was isolated in 41.2% of patients, Klebsiella pneumoniae (K pneumoniae) in 24.7%, and Proteus mirabilis (P mirabilis) in 15.3%. E coli microbial resistance rates ranged from a minimum of 7.5% (nitrofurantoin) to a maximum of 77.1% (ampicillin). In the case of K pneumoniae, microbial resistance ranged from 34.2% (netilmicin) to 73.2% (ceftriaxone). Resistance rates of P mirabilis ranged from 11.1% (cefepim) to 89.5% (ampicillin). Positivity of ESBL bacteria was identified in 47.4% of patients. Resistance rates of ESBL-positive E coli ranged from 50.0% (ceftriaxone) to 88.1% (cefepime), and ESBL-negative E coli rates ranged from 3.4% (cefepime) to 64.4% (amikacin). Resistance rates of ESBL-positive K pneumoniae ranged between 39.1% (netilmicin) and 85.1% (ceftriaxone), and ESBL-negative K pneumoniae between 7.1% (cefepime) and 53.3% (amikacin). In cases of ESBL-positive P mirabilis, rates ranged from 13.3% (cefepime) to 90.3% (ceftriaxone), whereas in cases of ESBL-negative P mirabilis, rates ranged between 8.3% (cefepime) and 80.0% (trimetroprim).Bacteriuria and asymptomatic catheter infection in chronic carriers is an important public health concern due to the frequent presence of multidrug-resistant bacteria. Our study highlights the need to develop control programs of catheter infections to minimize the risk of infections associated with these medical devices, and also the need for treatment of the infection rather than catheter colonization or contamination.
- Aminoglycoside Heteroresistance in Acinetobacter baumannii AB5075. [Journal Article]
- MmSphere 2018 Aug 15; 3(4)
- Heteroresistance is a phenomenon where a subpopulation of cells exhibits higher levels of antibiotic resistance than the general population. Analysis of tobramycin resistance in Acinetobacter baumann...
Heteroresistance is a phenomenon where a subpopulation of cells exhibits higher levels of antibiotic resistance than the general population. Analysis of tobramycin resistance in Acinetobacter baumannii AB5075 using Etest strips demonstrated that colonies with increased resistance arose at high frequency within the zone of growth inhibition. The presence of a resistant subpopulation was confirmed by population analysis profiling (PAP). The tobramycin-resistant subpopulation was cross resistant to gentamicin but not amikacin. The increased tobramycin resistance phenotype was highly unstable, and cells reverted to a less resistant population at frequencies of 60 to 90% after growth on nonselective media. Furthermore, the frequency of the resistant subpopulation was not increased by preincubation with subinhibitory concentrations of tobramycin. The tobramycin-resistant subpopulation was shown to replicate during the course of antibiotic treatment, demonstrating that these were not persister cells. In A. baumannii AB5075, a large plasmid (p1AB5075) carries aadB, a 2″-nucleotidyltransferase that confers resistance to both tobramycin and gentamicin but not amikacin. The aadB gene is part of an integron and is carried adjacent to four additional resistance genes that are all flanked by copies of an integrase gene. In isolates with increased resistance, this region was highly amplified in a RecA-dependent manner. However, in a recA mutant, colonies with unstable tobramycin resistance arose by a mechanism that did not involve amplification of this region. These data indicate that tobramycin heteroresistance occurs by at least two mechanisms in A. baumannii, and future studies to determine its effect on patient outcomes are warranted.IMPORTANCEAcinetobacter baumannii has become an important pathogen in hospitals worldwide, where the incidence of these infections has been increasing. A. baumannii infections have become exceedingly difficult to treat due to a rapid increase in the frequency of multidrug- and pan-resistant isolates. This has prompted the World Health Organization to list A. baumannii as the top priority for the research and development of new antibiotics. This study reports for the first time a detailed analysis of aminoglycoside heteroresistance in A. baumannii We define the mechanistic basis for heteroresistance, where the aadB(ant2″)Ia gene encoding an aminoglycoside adenylyltransferase becomes highly amplified in a RecA-dependent manner. Remarkably, this amplification of 20 to 40 copies occurs stochastically in 1/200 cells in the absence of antibiotic selection. In addition, we provide evidence for a second RecA-independent mechanism for aminoglycoside heteroresistance. This study reveals that aminoglycoside resistance in A. baumannii is far more complex than previously realized and has important implications for the use of aminoglycosides in treating A. baumannii infections.
- Treatment of Infections with OXA-48 producing Enterobacteriaceae. [Journal Article]
- AAAntimicrob Agents Chemother 2018 Aug 13
- Carbapenemase-producing Enterobacteriaceae (CPE) contribute significantly to the global public health threat of antimicrobial resistance. OXA-48, and its variants, are unique carbapenemases with low ...
Carbapenemase-producing Enterobacteriaceae (CPE) contribute significantly to the global public health threat of antimicrobial resistance. OXA-48, and its variants, are unique carbapenemases with low level hydrolytic activity toward carbapenems, but no intrinsic activity against expanded spectrum cephalosporins. blaOXA-48 is usually located on a plasmid, but may also be integrated chromosomally, and these genes have progressively disseminated throughout Europe and the Middle East. Despite the inability of OXA-48-like carbapenemases to hydrolyse expanded spectrum cephalosporins, pooled isolates demonstrate high variable resistance to ceftazidime and cefepime, respectively, likely to represent high rates of extended-spectrum beta-lactamase (ESBL) co-production. In-vitro data from pooled studies suggests that avibactam is the most potent beta-lactamase inhibitor when combined with ceftazidime, cefepime, aztreonam, meropenem or imipenem. Resistance to novel avibactam combinations such as imipenem/avibactam or aztreonam/avibactam has not yet been reported in OXA-48 producers, although only few clinical isolates have been tested. Although combination therapy is thought to improve chances of clinical cure and survival in CPE infection, successful outcomes were seen in ∼70% of patients with infections caused by OXA-48-producing Enterobacteriaceae treated with ceftazidime/avibactam monotherapy. A carbapenem in combination with either amikacin or colistin has achieved treatment success in a few case reports. Uncertainty remains over the best treatment options and strategies used to manage these infections. Newly available antibiotics such as ceftazidime/avibactam show promise, however recent reports of resistance are concerning. Newer choices of antimicrobial agents will likely be required to combat this problem.
- Prescribing Empiric Antibiotics for Febrile Neutropenia: Compliance with Institutional Febrile Neutropenia Guidelines. [Journal Article]
- PPharmacy (Basel) 2018 Aug 10; 6(3)
- Background: Febrile neutropenia (FN) is an oncologic emergency which should be treated immediately with empiric antibiotics. Different institutions observe different antibiograms and use different F...
Background: Febrile neutropenia (FN) is an oncologic emergency which should be treated immediately with empiric antibiotics. Different institutions observe different antibiograms and use different FN management guidelines. Our center implemented FN management guidelines for adult cancer patients in 2009. Hence, we decided to assess compliance with FN management guidelines and to describe the pattern of bacterial infections. Method: We conducted a cross-sectional study on all adult cancer patients admitted with FN. Data were collected from electronic medical records between January and December 2014. Results: One hundred FN episodes met the study inclusion criteria. The mean age of the patients was 41 ± 17 years; 52% (52 patients) were women. The most common diagnosis was lymphoma (33%). In terms of compliance to institutional FN guidelines, 55% of patients received guideline non-compliant treatment. The most common non-compliant treatment was incorrect amikacin dosing in 31% of patients, followed by incorrect vancomycin dosing in 20%, incorrect piperacillin/tazobactam dosing in 19%, inappropriate use of carbapenems in 18%, and non-compliant vancomycin use in 12% of patients. Bacterial isolates were only observed in 19% of the FN episodes. Among these 19 episodes of FN, Gram-negative pathogens were predominant and were identified in 74% of the episodes, followed by Gram-positive pathogens in 16% and polymicrobial pathogens in 10%. The mean time to defervescence was 2.21 ± 2 days. Conclusion: Our study concluded that there was a high percentage of non-compliance with our institutional FN management guidelines. We recommend following appropriate empiric antibiotic doses and indications as per institutional guidelines.
- Incidence of multidrug resistance and extended-spectrum beta-lactamase expression in community-acquired urinary tract infection among different age groups of patients. [Journal Article]
- IJIndian J Pharmacol 2018 Mar-Apr; 50(2):69-74
- CONCLUSIONS: It was concluded that for effective treatment of UTIs, appropriate screening of ESBL and culture sensitivity must be employed instead of empiric treatment.
- Effect of increasing meropenem MIC on the killing activity of meropenem in combination with amikacin or polymyxin B against MBL- and KPC-producing Enterobacter cloacae. [Journal Article]
- DMDiagn Microbiol Infect Dis 2018 Jun 22
- Carbapenem resistant Enterobacteriaceae (CRE) are a growing threat worldwide. Infections caused by these organisms have exhibited high rates of mortality (50%) for which there is no standard of care ...
Carbapenem resistant Enterobacteriaceae (CRE) are a growing threat worldwide. Infections caused by these organisms have exhibited high rates of mortality (50%) for which there is no standard of care and a dearth of clinical trials. Most in vitro data on CRE focus on Klebsiella pneumoniae, but it is known that effective therapy may depend on species or even strain. To address this, meropenem, amikacin, and polymyxin B alone and in combination were evaluated by time kill against four carbapenem-producing Enterobacter cloacae clinical isolates representing a range of meropenem nonsusceptibility (2-32 mg/L) and resistance mechanisms (KPC 2 and/or VIM 1). As meropenem minimum inhibitory concentration (MIC) increased, bactericidal activity and synergy were maintained for 48 hours in isolates exposed to meropenem and amikacin, but synergy and bactericidal activity were not maintained in all isolates exposed to meropenem and polymyxin B.
- NOCARDIOSIS: 7-YEAR experience at an australian tertiary hospital. [Journal Article]
- IMIntern Med J 2018 Aug 08
- CONCLUSIONS: In the largest Australian series in 25 years, nocardiosis predominantly affected patients with chronic lung disease or impaired cell-mediated immunity. A significant proportion of organisms from pulmonary sites were isolated on mycobacterial culture media only, suggesting that its use may improve yield. Isolates remain highly susceptible to sulfamethoxazole-trimethoprim, amikacin and imipenem, whilst other agents should be used only after confirmation of in vitro susceptibility. This article is protected by copyright. All rights reserved.
- Identification and Ranking of Clinical Compounds with Activity against Log-phase Growing Uropathogenic Escherichia coli. [Journal Article]
- CDCurr Drug Discov Technol 2018 Aug 07
- CONCLUSIONS: Our findings provide possible effective drug candidates for more effective treatment of antibiotic-resistant UTIs.
New Search Next
- Measuring the impact of varying denominator definitions on standardized antibiotic consumption rates: implications for antimicrobial stewardship programmes. [Journal Article]
- JAJ Antimicrob Chemother 2018 Aug 06
- CONCLUSIONS: We found that data source and definitions of at-risk denominator days meaningfully impact antibiotic SCRs. Centres should carefully consider these potential sources of variation when setting consumption benchmarks and internally evaluating use.