scholarly journals Predictors of Mortality in Patients with Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae: Importance of Inadequate Initial Antimicrobial Treatment

2007 ◽  
Vol 51 (6) ◽  
pp. 1987-1994 ◽  
Author(s):  
Mario Tumbarello ◽  
Maurizio Sanguinetti ◽  
Eva Montuori ◽  
Enrico M. Trecarichi ◽  
Brunella Posteraro ◽  
...  
Keyword(s):  
Antimicrobial Therapy ◽  
Antimicrobial Agents ◽  
Cohort Analysis ◽  
Bloodstream Infections ◽  
Treated Group ◽  
Antimicrobial Treatment ◽  
Predictors Of Mortality ◽  
Extended Spectrum ◽  
Initial Antimicrobial Therapy ◽  
The Impact

ABSTRACT Bloodstream infections (BSI) caused by extended-spectrum β-lactamase (ESBL)-producing organisms markedly increase the rates of treatment failure and death. We conducted a retrospective cohort analysis to identify risk factors for mortality in adult in-patients with BSI caused by ESBL-producing Enterobacteriaceae (ESBL-BSI). Particular attention was focused on defining the impact on the mortality of inadequate initial antimicrobial therapy (defined as the initiation of treatment with active antimicrobial agents >72 h after collection of the first positive blood culture). A total of 186 patients with ESBL-BSI caused by Escherichia coli (n = 104), Klebsiella pneumoniae (n = 58), or Proteus mirabilis (n = 24) were identified by our microbiology laboratory from 1 January 1999 through 31 December 2004. The overall 21-day mortality rate was 38.2% (71 of 186). In multivariate analysis, significant predictors of mortality were inadequate initial antimicrobial therapy (odds ratio [OR] = 6.28; 95% confidence interval [CI] = 3.18 to 12.42; P < 0.001) and unidentified primary infection site (OR = 2.69; 95% CI = 1.38 to 5.27; P = 0.004). The inadequately treated patients (89 of 186 [47.8%]) had a threefold increase in mortality compared to the adequately treated group (59.5% versus 18.5%; OR = 2.38; 95% CI = 1.76 to 3.22; P < 0.001). The regimens most commonly classified as inadequate were based on oxyimino cephalosporin or fluoroquinolone therapy. Prompt initiation of effective antimicrobial treatment is essential in patients with ESBL-BSI, and empirical decisions must be based on a sound knowledge of the local distribution of pathogens and their susceptibility patterns.

scholarly journals Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase- Producing Escherichia coli: Risk Factors for Inadequate Initial Antimicrobial Therapy

2008 ◽  
Vol 52 (9) ◽  
pp. 3244-3252 ◽  
Author(s):  
Mario Tumbarello ◽  
Michela Sali ◽  
Enrico Maria Trecarichi ◽  
Fiammetta Leone ◽  
Marianna Rossi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Escherichia Coli ◽  
Antimicrobial Therapy ◽  
Bloodstream Infections ◽  
Disease Epidemiology ◽  
E Coli ◽  
Infectious Disease Epidemiology ◽  
Extended Spectrum ◽  
Initial Antimicrobial Therapy

ABSTRACT Extended-spectrum-β-lactamase (ESBL)-producing strains of Escherichia coli are a significant cause of bloodstream infections (BSI) in hospitalized and nonhospitalized patients. We previously showed that delaying effective antimicrobial therapy in BSI caused by ESBL producers significantly increases mortality. The aim of this retrospective 7-year analysis was to identify risk factors for inadequate initial antimicrobial therapy (IIAT) (i.e., empirical treatment based on a drug to which the isolate had displayed in vitro resistance) for inpatients with BSI caused by ESBL-producing E. coli. Of the 129 patients considered, 56 (43.4%) received IIAT for 48 to 120 h (mean, 72 h). Independent risk factors for IIAT include an unknown BSI source (odds ratios [OR], 4.86; 95% confidence interval [CI], 1.98 to 11.91; P = 0.001), isolate coresistance to ≥3 antimicrobials (OR, 3.73; 95% CI, 1.58 to 8.83; P = 0.003), hospitalization during the 12 months preceding BSI onset (OR, 3.33; 95% CI, 1.42 to 7.79; P = 0.005), and antimicrobial therapy during the 3 months preceding BSI onset (OR, 2.65; 95% CI, 1.11 to 6.29; P = 0.02). IIAT was the strongest risk factor for 21-day mortality and significantly increased the length of hospitalization after BSI onset. Our results underscore the need for a systematic approach to the management of patients with serious infections by ESBL-producing E. coli. Such an approach should be based on sound, updated knowledge of local infectious-disease epidemiology, detailed analysis of the patient's history with emphasis on recent contact with the health care system, and aggressive attempts to identify the infectious focus that has given rise to the BSI.

scholarly journals The Effect of pH on Antibiotic Efficacy against Coxiella burnetii in Axenic Media

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Cody B. Smith ◽  
Charles Evavold ◽  
Gilbert J. Kersh
Keyword(s):  
Coxiella Burnetii ◽  
Antimicrobial Agents ◽  
Q Fever ◽  
Antimicrobial Treatment ◽  
Etiologic Agent ◽  
Growth And Survival ◽  
Intracellular Compartments ◽  
The Impact

AbstractCoxiella burnetii, the etiologic agent of Q fever, replicates in an intracellular phagolysosome with pH between 4 and 5. The impact of this low pH environment on antimicrobial treatment is not well understood. An in vitro system for testing antibiotic susceptibility of C. burnetii in axenic media was set up to evaluate the impact of pH on C. burnetii growth and survival in the presence and absence of antimicrobial agents. The data show that C. burnetii does not grow in axenic media at pH 6.0 or higher, but the organisms remain viable. At pH of 4.75, 5.25, and 5.75 moxifloxacin, doxycycline, and rifampin are effective at preventing growth of C. burnetii in axenic media, with moxifloxacin and doxycycline being bacteriostatic and rifampin having bactericidal activity. The efficacy of doxycycline and moxifloxacin improved at higher pH, whereas rifampin activity was pH independent. Hydroxychloroquine is thought to inhibit growth of C. burnetii in vivo by raising the pH of typically acidic intracellular compartments. It had no direct bactericidal or bacteriostatic activity on C. burnetii in axenic media, suggesting that raising pH of acidic intracellular compartments is its primary mechanism of action in vivo. The data suggest that doxycycline and hydroxychloroquine are primarily independent bacteriostatic agents.

scholarly journals Antimicrobial Treatment Options for Granulomatous Mastitis Caused by Corynebacterium Species

2015 ◽  
Vol 53 (9) ◽  
pp. 2895-2899 ◽  
Author(s):  
Hazel C. Dobinson ◽  
Trevor P. Anderson ◽  
Stephen T. Chambers ◽  
Matthew P. Doogue ◽  
Lois Seaward ◽  
...  
Keyword(s):  
Antimicrobial Therapy ◽  
Breast Tissue ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Antimicrobial Treatment ◽  
Granulomatous Mastitis ◽  
Sensitivity Testing ◽  
Treatment Protocols ◽  
Content Type ◽  
16S Rna

Corynebacteriumspecies are increasingly recognized as important pathogens in granulomatous mastitis. Currently, there are no published treatment protocols forCorynebacteriumbreast infections. This study describes antimicrobial treatment options in the context of other management strategies used for granulomatous mastitis.Corynebacteriumspp. isolated from breast tissue and aspirate samples stored from 2002 to 2013 were identified and determined to the species level using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), 16S RNA sequencing, andrpoBgene targets. The MICs for 12 antimicrobials were performed using Etest for each isolate. Correlations of these with antimicrobial characteristics, choice of antimicrobial, and disease outcome were evaluated.Corynebacteriumspp. from breast tissue and aspirate samples were confirmed in 17 isolates from 16 patients. Based on EUCAST breakpoints,Corynebacterium kroppenstedtiiisolates (n= 11) were susceptible to seven antibiotic classes but resistant to β-lactam antibiotics.Corynebacterium tuberculostearicumisolates (n= 4) were multidrug resistant. Two nonlipophilic species were isolated,Corynebacterium glucuronolyticumandCorynebacterium freneyi, both of which have various susceptibilities to antimicrobial agents. Short-course antimicrobial therapy was common (median, 6 courses per subject; range, 1 to 9 courses). Patients withC. kroppenstedtiipresented with a hot painful breast mass and underwent multiple surgical procedures (median, 4 procedures; range, 2 to 6 procedures). The management ofCorynebacteriumbreast infections requires a multidisciplinary approach and includes culture and appropriate sensitivity testing to guide antimicrobial therapy. Established infections have a poor outcome, possibly because adequate concentrations of some drugs will be difficult to achieve in lipophilic granulomata. Lipophilic antimicrobial therapy may offer a therapeutic advantage. The role of immunotherapy has not been defined.

scholarly journals Impact of Inadequate Initial Antimicrobial Therapy on Mortality in Infections Due to Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae

2005 ◽  
Vol 165 (12) ◽  
pp. 1375 ◽  
Author(s):  
Emily P. Hyle ◽  
Adam D. Lipworth ◽  
Theoklis E. Zaoutis ◽  
Irving Nachamkin ◽  
Warren B. Bilker ◽  
...  
Keyword(s):  
Antimicrobial Therapy ◽  
Extended Spectrum ◽  
Initial Antimicrobial Therapy

scholarly journals Bloodstream Infections Due to Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae: Risk Factors for Mortality and Treatment Outcome, with Special Emphasis on Antimicrobial Therapy

2004 ◽  
Vol 48 (12) ◽  
pp. 4574-4581 ◽  
Author(s):  
Cheol-In Kang ◽  
Sung-Han Kim ◽  
Wan Beom Park ◽  
Ki-Deok Lee ◽  
Hong-Bin Kim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Escherichia Coli ◽  
Treatment Outcome ◽  
Klebsiella Pneumoniae ◽  
Antimicrobial Therapy ◽  
Bloodstream Infections ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum ◽  
Empirical Antimicrobial Therapy

ABSTRACT This study was conducted to evaluate risk factors for mortality and treatment outcome of bloodstream infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK). ESBL production in stored K. pneumoniae and E. coli blood isolates from Jan 1998 to Dec 2002 was phenotypically determined according to NCCLS guidelines and/or the double-disk synergy test. A total of 133 patients with ESBL-EK bacteremia, including 66 patients with ESBL-producing K. pneumoniae and 67 with ESBL-producing E. coli, were enrolled. The overall 30-day mortality rate was 25.6% (34 of 133). Independent risk factors for mortality were severe sepsis, peritonitis, neutropenia, increasing Acute Physiology and Chronic Health Evaluation II score, and administration of broad-spectrum cephalosporin as definitive antimicrobial therapy (P < 0.05 for each of these risk factors). In 117 of the 133 patients, excluding 16 patients who died within 3 days after blood culture sample acquisition, the 30-day mortality rates according to definitive antibiotics were as follows: carbapenem, 12.9% (8 of 62); ciprofloxacin, 10.3% (3 of 29); and others, such as cephalosporin or an aminoglycoside, 26.9% (7 of 26). When patients who received appropriate definitive antibiotics, such as carbapenem or ciprofloxacin, were evaluated, mortality in patients receiving inappropriate empirical antimicrobial therapy was found not to be significantly higher than mortality in those receiving appropriate empirical antimicrobial therapy (18.9 versus 15.5%; P = 0.666). Carbapenem and ciprofloxacin were the most effective antibiotics in antimicrobial therapy for ESBL-EK bacteremia. A delay in appropriate definitive antimicrobial therapy was not associated with higher mortality if antimicrobial therapy was adjusted appropriately according to the susceptibility results. Our data suggest that more prudent use of carbapenem as empirical antibiotic may be reasonable.

scholarly journals Bloodstream Infections Caused by Antibiotic-Resistant Gram-Negative Bacilli: Risk Factors for Mortality and Impact of Inappropriate Initial Antimicrobial Therapy on Outcome

2005 ◽  
Vol 49 (2) ◽  
pp. 760-766 ◽  
Author(s):  
Cheol-In Kang ◽  
Sung-Han Kim ◽  
Wan Beom Park ◽  
Ki-Deok Lee ◽  
Hong-Bin Kim ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Mortality Rate ◽  
Antimicrobial Therapy ◽  
Treated Group ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Gram Negative Bacteremia ◽  
Initial Antimicrobial Therapy ◽  
Risk Source

ABSTRACT The marked increase in the incidence of infections due to antibiotic-resistant gram-negative bacilli in recent years is of great concern, as patients infected by those isolates might initially receive antibiotics that are inactive against the responsible pathogens. To evaluate the effect of inappropriate initial antimicrobial therapy on survival, a total of 286 patients with antibiotic-resistant gram-negative bacteremia, 61 patients with Escherichia coli bacteremia, 65 with Klebsiella pneumoniae bacteremia, 74 with Pseudomonas aeruginosa bacteremia, and 86 with Enterobacter bacteremia, were analyzed retrospectively. If a patient received at least one antimicrobial agent to which the causative microorganisms were susceptible within 24 h of blood culture collection, the initial antimicrobial therapy was considered to have been appropriate. High-risk sources of bacteremia were defined as the lung, peritoneum, or an unknown source. The main outcome measure was 30-day mortality. Of the 286 patients, 135 (47.2%) received appropriate initial empirical antimicrobial therapy, and the remaining 151 (52.8%) patients received inappropriate therapy. The adequately treated group had a 27.4% mortality rate, whereas the inadequately treated group had a 38.4% mortality rate (P = 0.049). Multivariate analysis showed that the significant independent risk factors of mortality were presentation with septic shock, a high-risk source of bacteremia, P. aeruginosa infection, and an increasing APACHE II score. In the subgroup of patients (n = 132) with a high-risk source of bacteremia, inappropriate initial antimicrobial therapy was independently associated with increased mortality (odds ratio, 3.64; 95% confidence interval, 1.13 to 11.72; P = 0.030). Our data suggest that inappropriate initial antimicrobial therapy is associated with adverse outcome in antibiotic-resistant gram-negative bacteremia, particularly in patients with a high-risk source of bacteremia.

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