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1.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(11): 1028-1031, 2020 Nov 25.
Article in Chinese | MEDLINE | ID: mdl-33212549

ABSTRACT

Most abdominal infections are mixed infections caused by aerobic and anaerobic bacteria. Anaerobic infections are characterized by rancid secretions or abscess formation. Early implementation of source control is the key in the treatment of abdominal anaerobic infections. Damage control should be followed as one of the principles of surgical treatment. As the in vitro isolation and culture of anaerobic bacteria as well as its drug sensitivity test are time-consuming and sometimes inaccurate, the treatment of anaerobic bacteria infection is mostly empirical. Anti-infective therapy should be employed once anaerobic bacteria infection is confirmed. Ertapenem, Mosifloxacin, and Cefoperazone-sulbactam can be used for first-line monotherapy, while combination therapy can use second- or third-generation Cephalosporin, Quinolones plus Nitroimidazoles. Nutritional support and anti-shock treatment should not be neglected when implementing surgical control of infection source and antimicrobial therapy. Considering the increasing drug resistance of anaerobic bacteria, and the higher drug resistance rate in China as compared to western countries, the choice of antibiotics should be made rationally and based on epidemiological characteristics of anaerobic bacteria in different regions.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteria, Anaerobic , Bacterial Infections , Intraabdominal Infections/therapy , Bacteria, Anaerobic/drug effects , Bacteria, Anaerobic/isolation & purification , Bacterial Infections/etiology , Bacterial Infections/microbiology , Bacterial Infections/therapy , Drug Resistance, Bacterial , Humans , Intraabdominal Infections/etiology , Intraabdominal Infections/microbiology , Microbial Sensitivity Tests
2.
Expert Rev Anti Infect Ther ; 17(11): 851-863, 2019 11.
Article in English | MEDLINE | ID: mdl-31622119

ABSTRACT

Introduction: Complicated intra-abdominal infections (cIAIs) are among the most frequent infections, contributing to significant morbidity and healthcare costs. Several medical needs remain unmet, related to the pharmacokinetic capacities of the available drugs and their limited spectrum of activity for targeting multidrug-resistant Gram-negative and Gram-positive bacteria. Eravacycline, a new synthetic fluorocycline, could have useful properties in cIAIs.Areas covered: The antimicrobial activity of eravacycline against the microorganisms most frequently cultured in cIAIs has been confirmed in worldwide panels of clinical isolates, including enterococci, ESBL-producing Enterobacteriaceae, Acinetobacter baumannii and anaerobes. Pharmacokinetic data demonstrate interesting characteristics with good tissue concentrations including biliary tract and digestive tissues. At a conventional dosage of 1 mg/kg q12h, no adjustment is required on the basis of race or gender, or in elderly (≥ 65 years old) patients, patients with renal impairment or patients undergoing hemodialysis. Phase 2 and 3 trials assessing the clinical efficacy and safety of eravacycline demonstrated non-inferiority versus carbapenems and a good safety profile.Expert opinion: Eravacycline may be particularly suitable for the treatment of cIAIs. Results from clinical trials and real-world data are now expected in specific subgroups of patients to confirm the safety profile and efficacy observed in registration trials.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Intraabdominal Infections/drug therapy , Tetracyclines/administration & dosage , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacokinetics , Bacteria/drug effects , Bacteria/isolation & purification , Dose-Response Relationship, Drug , Humans , Intraabdominal Infections/microbiology , Microbial Sensitivity Tests , Tetracyclines/adverse effects , Tetracyclines/pharmacokinetics
3.
Future Microbiol ; 14: 1293-1308, 2019 10.
Article in English | MEDLINE | ID: mdl-31570004

ABSTRACT

Aim: Recently approved for use in complicated intra-abdominal infection, eravacycline is a novel fluorocycline with broad spectrum of activity against resistant Gram-negative pathogens. This manuscript is a pooled analysis of two Phase III trials. Clinical efficacy: Clinical cure rates were 86.8% for eravacycline versus 87.6% for ertapenem, and 90.8% for eravacycline versus 91.2% for meropenem in the Intent to Treat (micro-ITT) populations, and 87.0% for eravacycline versus 88.8% ertapenem, and 92.4 versus 91.6% for meropenem in the Modified Intent to Treat (MITT) populations. Safety: Eravacycline is well tolerated, with lower rates of nausea, vomiting and diarrhea than other tetracyclines. Conclusion: Eravacycline is an effective new option for use in complicated intra-abdominal infections, and in particular, for the treatment of extended-spectrum ß-lactamase- and carbapenem-resistant Enterobacteriaceae-expressing organisms.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Resistance, Multiple, Bacterial , Enterobacteriaceae/drug effects , Intraabdominal Infections/drug therapy , Intraabdominal Infections/microbiology , Tetracyclines/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Carbapenems/therapeutic use , Data Interpretation, Statistical , Enterobacteriaceae/enzymology , Ertapenem/therapeutic use , Female , Humans , Intraabdominal Infections/complications , Male , Meropenem/therapeutic use , Microbial Sensitivity Tests , Middle Aged , Prospective Studies , Young Adult , beta-Lactamases
4.
J Gastroenterol Hepatol ; 34(12): 2096-2103, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31157455

ABSTRACT

BACKGROUND AND AIM: In contrast to the first peak of multi-organ failure in acute pancreatitis, the second peak is mostly triggered by septic complications. Our aim was to analyze the spectrum of pathogens and antimicrobial resistance development in relation to the time-course of the disease and its clinical outcome. METHODS: One hundred twenty-two patients with acute necrotizing pancreatitis undergoing pancreas puncture at two tertiary academic medical centers in Germany were retrospectively analyzed. RESULTS: At species level, there was a change in spectrum from Enterococcus faecalis (∆d150 - d1 = 14.6% - 16.7% = -2.1%) to Enterococcus faecium (∆d150 - d1 = 93.1% - 16.3% = 76.8%) (P < 0.001) and from Candida albicans (∆d150 - d1 = 39.7% - 23.6% = 16.1%) to non-albicans Candida spp. (∆d150 - d1 = 43.5% - 6.4% = 37.1%) (P = 0.005). Time-to-event analysis of acquired antimicrobial resistance showed that the overall number of patients with Enterobacteriaceae presented an antimicrobial susceptibility decrease by 59.7% (∆d1 - d100 = 87.0% - 27.3% = 59.7%). The cumulative incidence of multi-resistant bacteria increased with length of hospital stay (∆d150 - d1 = 49.1% - 3.1% = 46.0%) (P = 0.004). Multivariable logistic regression analysis in relation to the pathogen spectrum and antimicrobial resistance development showed a significantly higher mortality for non-albicans Candida spp. (P = 0.039, odds ratio [OR] = 3.32 [95% confidence interval [CI]: 1.07-10.35]), E. faecium (P = 0.009, OR = 3.73 [95% CI: 1.38-10.05]), and multi-resistant bacteria (P = 0.007, OR = 5.08 [95% CI: 1.55-16.66]). CONCLUSIONS: Antimicrobial treatment of infected pancreatic necrosis becomes more challenging over time, owing to a change in spectrum favoring difficult-to-treat pathogens and an increase in multi-resistant bacteria associated with worse clinical outcomes (World Health Organization trial registration number: DRKS00014785).


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/complications , Pancreatitis, Acute Necrotizing/complications , Pancreatitis, Acute Necrotizing/drug therapy , Adult , Aged , Aged, 80 and over , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Bacterial Typing Techniques , Candida/classification , Candida/drug effects , Candida/isolation & purification , Drug Resistance, Bacterial , Drug Resistance, Multiple, Bacterial , Enterobacteriaceae/classification , Enterobacteriaceae/drug effects , Enterobacteriaceae/isolation & purification , Female , Humans , Length of Stay , Male , Microbial Sensitivity Tests/methods , Middle Aged , Retrospective Studies , Young Adult
5.
Article in Chinese | WPRIM | ID: wpr-790101

ABSTRACT

Objective To explore the application value of early postoperative enteral eco-immune nutrition in the nutritional support treatment for intra-abdominal infection.Methods The prospective study was conducted.The clinicopathological data of 62 patients with intra-abdominal infection who were admitted to the 940 Hospital of the People's Liberation Army Joint Service Support Force from February 2018 to December 2018 were collected.All patients were randomly divided into two groups by the envelope method with double-blind technique,including patients who began being given enteral eco-immune nutrition preparation at postoperative 24-48 hours in eco-immune group and patients who began being given simple enteral nutrition preparation at 24-48 hours in control group.Observation indicators:(1) analysis of immune function indices before treatment and after 7 days of treatment in the two groups;(2) postoperative conditions in the two groups;(3) follow-up.Follow-up using telephone interview was performed to detect complications and recurrence of infection up to May 2019.Measurement data with normal distribution were represented as Mean ± SD,and intra-group comparison and comparison between groups were analyzed using the t test.Count data were represented as absolute numbers or percentages,and comparison between groups was analyzed using the chi-square test.Results Sixty-two patients were screened for eligibility,including 38 males and 24 females,aged (54± 14)years,with the range of 22-81 years.There were 30 in the eco-immune group and 32 in the control group.(1) Analysis of immune function indices before treatment and after 7 days of treatment in the two groups:before treatment,the percentages of CD3+,CD4+,CD8+,ratio of CD4+/CD8+,count of natural killer (NK) cells,levels of blood endotoxin and immunoglobulin A (IgA) for the eco-immune group were 61% ± 12%,34% ± 5%,28% ± 5%,1.25 ± 0.34,17.26%±2.74%,(2.4±0.3)ng/L,and (1.7±0.5)g/L,versus 59%±11%,33%±5%,27%±4%,1.27± 0.36,16.96% ±2.99%,(2.5± 0.5) ng/L,(1.8± 0.5) g/L for the control group,respectively,there were no significant differences between the two groups (t =-0.563,-0.354,-0.987,0.327,-0.462,0.887,0.991,P> 0.05).After 7 days of treatment,the above indices for the eco-immune group were 62%±8%,37%±6%,27%± 8%,1.45±0.32,22.63%±7.25%,(2.2±0.4) ng/L,and (2.3±0.4) g/L,versus 58%±8%,32%±4%,27% ±6%,1.26±0.22,16.26%±2.10%,(2.7±0.6)ng/L,and (2.0±0.4)g/L for the control group,respectively,there were significant differences in the percentages of CD3+,CD4+,ratio of CD4+/CD8+,count of NK cells,levels of blood endotoxin and IgA (t =-2.393,-4.336,-3.074,-5.338,4.010,-3.155,P<0.05),but no significant difference in the percentage of CD8+ between the two groups (t =0.077,P>0.05).In the coo-immune group,the percentage of CD4+,ratio of CD4+/CD8+,count of NK cells,levels of blood endotoxin and IgA showed significant differences after 7 days of treatment (t =-2.899,-2.739,-4.385,2.157,-5.788,P<0.05),but the percentages of CD3+ and CD8+ showed no significant differences after 7 days of treatment (t =-0.490,1.193,P> 0.05).In the control group,the percentage of CD8+ and level of IgA showed significant differences after 7 days of treatment (t=3.659,-2.258,P<0.05),but the percentage of CD4+,ratio of CD4+/CD8+,count of NK cells,and level of blood endotoxin showed no significant differences after 7 days of treatment (t =0.157,0.759,1.132,1.212,-0.532,P>0.05).(2) Postoperative conditions in the two groups:the time to first flatus and duration of postoperative hospital stay of the eco-immune group were (2.4± 0.5) days and (8± 4) days,respectively,versus (2.9±0.7)days and (11±7)days of the control group;there were significant differences in the above indices between the two groups (t =-3.017,-2.764,P<0.05).In the eco-immune group,the incidence of complication was 6.7%(2/30),including 1 case of wound infection,1 case of pulmonary infection.In the control group,the incidence of complication was 31.2% (10/32),including 6 cases of wound infection,2 cases of pulmonary infection,1 case of intra-abdominal infection,and 1 case of systemic inflammatory response syndrome.There was a significant difference in the incidence of complication between the two groups (x2=4.122,P< 0.05).The patients with infection were recovered after corresponding systematic conservative treatments.(3) Follow-up:of the 62 patients,46 were followed up for 3-9 months,with a median follow-up time of 6 months,including 26 in the eco-immune group and 20 in the control group.During the follow-up,no complication or infection recurred in the two groups.Conclusion Compared with simple enteral nutrition,early postoperative enteral eco-immune nutrition in the nutritional support treatment is safe and effective for patients with intra-abdominal infection,which can enhance the immune function of patients,shorten the recovery time of patients,and reduce the incidence of infection complications.

6.
Article in Chinese | WPRIM | ID: wpr-796794

ABSTRACT

Objective@#To explore the application value of early postoperative enteral eco-immune nutrition in the nutritional support treatment for intra-abdominal infection.@*Methods@#The prospective study was conducted. The clinicopathological data of 62 patients with intra-abdominal infection who were admitted to the 940 Hospital of the People′s Liberation Army Joint Service Support Force from February 2018 to December 2018 were collected. All patients were randomly divided into two groups by the envelope method with double-blind technique, including patients who began being given enteral eco-immune nutrition preparation at postoperative 24-48 hours in eco-immune group and patients who began being given simple enteral nutrition preparation at 24-48 hours in control group. Observation indicators: (1) analysis of immune function indices before treatment and after 7 days of treatment in the two groups; (2) postoperative conditions in the two groups; (3) follow-up. Follow-up using telephone interview was performed to detect complications and recurrence of infection up to May 2019. Measurement data with normal distribution were represented as Mean±SD, and intra-group comparison and comparison between groups were analyzed using the t test. Count data were represented as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test.@*Results@#Sixty-two patients were screened for eligibility, including 38 males and 24 females, aged (54±14)years, with the range of 22-81 years. There were 30 in the eco-immune group and 32 in the control group. (1) Analysis of immune function indices before treatment and after 7 days of treatment in the two groups: before treatment, the percentages of CD3+, CD4+, CD8+, ratio of CD4+ /CD8+, count of natural killer (NK) cells, levels of blood endotoxin and immunoglobulin A (IgA) for the eco-immune group were 61%±12%, 34%±5%, 28%±5%, 1.25±0.34, 17.26%±2.74%, (2.4±0.3)ng/L, and (1.7±0.5)g/L, versus 59%±11%, 33%±5%, 27%±4%, 1.27±0.36, 16.96%±2.99%, (2.5±0.5)ng/L, (1.8±0.5)g/L for the control group, respectively, there were no significant differences between the two groups (t=-0.563, -0.354, -0.987, 0.327, -0.462, 0.887, 0.991, P>0.05). After 7 days of treatment, the above indices for the eco-immune group were 62%±8%, 37%±6%, 27%±8%, 1.45±0.32, 22.63%±7.25%, (2.2±0.4)ng/L, and (2.3±0.4)g/L, versus 58%±8%, 32%±4%, 27%±6%, 1.26±0.22, 16.26%±2.10%, (2.7±0.6)ng/L, and (2.0±0.4)g/L for the control group, respectively, there were significant differences in the percentages of CD3+, CD4+, ratio of CD4+ /CD8+, count of NK cells, levels of blood endotoxin and IgA (t=-2.393, -4.336, -3.074, -5.338, 4.010, -3.155, P<0.05), but no significant difference in the percentage of CD8+ between the two groups (t=0.077, P>0.05). In the eco-immune group, the percentage of CD4+, ratio of CD4+ /CD8+, count of NK cells, levels of blood endotoxin and IgA showed significant differences after 7 days of treatment (t=-2.899, -2.739, -4.385, 2.157, -5.788, P<0.05), but the percentages of CD3+ and CD8+ showed no significant differences after 7 days of treatment (t=-0.490, 1.193, P>0.05). In the control group, the percentage of CD8+ and level of IgA showed significant differences after 7 days of treatment (t=3.659, -2.258, P<0.05), but the percentage of CD4+, ratio of CD4+ /CD8+, count of NK cells, and level of blood endotoxin showed no significant differences after 7 days of treatment (t=0.157, 0.759, 1.132, 1.212, -0.532, P>0.05). (2) Postoperative conditions in the two groups: the time to first flatus and duration of postoperative hospital stay of the eco-immune group were (2.4±0.5)days and (8±4)days, respectively, versus (2.9±0.7)days and (11±7)days of the control group; there were significant differences in the above indices between the two groups (t=-3.017, -2.764, P<0.05). In the eco-immune group, the incidence of complication was 6.7%(2/30), including 1 case of wound infection, 1 case of pulmonary infection. In the control group, the incidence of complication was 31.2%(10/32), including 6 cases of wound infection, 2 cases of pulmonary infection, 1 case of intra-abdominal infection, and 1 case of systemic inflammatory response syndrome. There was a significant difference in the incidence of complication between the two groups (χ2=4.122, P<0.05). The patients with infection were recovered after corresponding systematic conservative treatments. (3) Follow-up: of the 62 patients, 46 were followed up for 3-9 months, with a median follow-up time of 6 months, including 26 in the eco-immune group and 20 in the control group. During the follow-up, no complication or infection recurred in the two groups.@*Conclusion@#Compared with simple enteral nutrition, early postoperative enteral eco-immune nutrition in the nutritional support treatment is safe and effective for patients with intra-abdominal infection, which can enhance the immune function of patients, shorten the recovery time of patients, and reduce the incidence of infection complications.

7.
BMC Infect Dis ; 18(1): 584, 2018 Nov 19.
Article in English | MEDLINE | ID: mdl-30453893

ABSTRACT

BACKGROUND: The aim was to evaluate the value of organ-specific weighted incidence antibiogram (OSWIA) percentages for bacterial susceptibilities of Gram-negative bacteria (GNB) collected from intra-abdominal infections (IAIs) during SMART 2010-2014. METHODS: We retrospectively calculated the OSWIA percentages that would have been adequately covered by 12 common antimicrobials based on the bacterial compositions found in the appendix, peritoneum, colon, liver, gall bladder and pancreas. RESULTS: The ESBL positive rates were 65.7% for Escherichia coli, 36.2% for Klebsiella pneumoniae, 42.9% for Proteus mirabilis and 33.1% for Klebsiella oxytoca. Escherichia coli were mainly found in the appendix (76.8%), but less so in the liver (32.4%). Klebsiella pneumoniae constituted 45.2% of the total liver pathogenic bacteria and 15.2-20.8% were found in 4 other organs, except the colon and appendix (< 10%). The percentages of Pseudomonas aeruginosa infections were higher in the gall bladder, intra-abdominal abscesses, pancreas and colon (10.2-13.2%) and least (5.4%) in the appendix. The susceptibilities of hospital acquired (HA) and community acquired (CA) IAI isolates from appendix, gall bladder and liver showed ≥80% susceptibilities to amikacin (AMK), imipenem (IPM), piperacillin-tazobactam (TZP) and ertapenem (ETP), while the susceptibility of isolates in abscesses and peritoneal fluid showed ≥80% susceptibility only to amikacin (AMK) and imipenem (IPM). In colon CA IAI isolates susceptibilities did not reach 80% for AMK and ETP, and in pancreatic IAIs susceptibilities of HA GNBs did not reach 80% to AMK, TZP and ETP, and CA GNBs to IMP and ETP. In addition, besides circa 80% susceptibility of HA and CA IAI isolates from appendix to cefoxitin (FOX), IAI isolates from all other organs had susceptibilities between 7.6 and 67.9% to all cephalosporins tested, 28.3-75.2% to fluoroquinolones and 7.6-51.0% to ampicillin-sulbactam (SAM), whether they were obtained from CA or HA infections. CONCLUSION: The calculated OSWIA susceptibilities were specific for different organs in abdominal infections.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Load/methods , Intraabdominal Infections/drug therapy , Intraabdominal Infections/microbiology , Microbial Sensitivity Tests/methods , Organ Specificity , China/epidemiology , Cross Infection/epidemiology , Cross Infection/microbiology , Drug Resistance, Bacterial , Gram-Negative Bacteria/classification , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacteria/pathogenicity , Humans , Intraabdominal Infections/classification , Intraabdominal Infections/epidemiology , Microbial Sensitivity Tests/standards , Organ Specificity/drug effects , Research Design , Retrospective Studies , Syndrome
8.
Hepatobiliary Pancreat Dis Int ; 17(5): 456-460, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30197163

ABSTRACT

BACKGROUND: Acute pancreatitis (AP) continues to cause significant morbidity and mortality, especially when it leads to infected pancreatic necrosis (IPN). Modern treatment of IPN frequently involves prolonged courses of antibiotics in combination with minimally invasive therapies. This study aimed to update the existing evidence base by identifying the pathogens causing IPN and therefore aid future selection of empirical antibiotics. METHODS: Clinical data, including microbiology results, of consecutive patients with IPN undergoing minimally invasive necrosectomy at our institution between January 2009 and July 2016 were retrospectively reviewed. RESULTS: The results of 40 patients (22 males and 18 females, median age 60 years) with IPN were reviewed. The etiology of AP was gallstones, alcohol, dyslipidemia and unknown in 31, 2, 2 and 5 patients, respectively. The most frequently identified microbes in microbiology cultures were Enterococcus faecalis and faecium (22.5% and 20.0%) and Escherichia coli (20.0%). In 19 cases the cultures grew multiple organisms. The antibiotics with the least resistance amongst the microbiota were teicoplanin (5.0%), linezolid (5.6%), ertapenem (6.5%), and meropenem (7.4%). CONCLUSION: The carbapenem antibiotics, ertapenem and meropenem provide good antimicrobial cover against the common, mainly enteral, microorganisms causing IPN. Culture and sensitivity results of acquired samples should be regularly reviewed to adjust prescribing and monitor for emergence of resistance.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/isolation & purification , Pancreatitis, Acute Necrotizing/drug therapy , Pancreatitis, Acute Necrotizing/microbiology , Adult , Aged , Anti-Bacterial Agents/pharmacology , Cohort Studies , Databases, Factual , Drainage/methods , Drug Therapy, Combination , Female , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Infusions, Intravenous , Male , Microbial Sensitivity Tests , Middle Aged , Pancreatitis, Acute Necrotizing/mortality , Pancreatitis, Acute Necrotizing/surgery , Prognosis , Retrospective Studies , Severity of Illness Index , Survival Rate , Tertiary Care Centers , Treatment Outcome
9.
Article in English | MEDLINE | ID: mdl-29686147

ABSTRACT

The increasing prevalence of multidrug-resistant Gram-negative pathogens has generated a requirement for new treatment options. Avibactam, a novel non-ß-lactam-ß-lactamase inhibitor, restores the activity of ceftazidime against Ambler class A, C, and some class D ß-lactamase-producing strains of Enterobacteriaceae and Pseudomonas aeruginosa The in vitro activities of ceftazidime-avibactam versus comparators were evaluated against 1,440 clinical isolates obtained in a phase 3 clinical trial in patients with complicated intra-abdominal infections (cIAI; ClinicalTrials.gov identifier NCT01499290). Overall, in vitro activities were determined for 803 Enterobacteriaceae, 70 P. aeruginosa, 304 Gram-positive aerobic, and 255 anaerobic isolates obtained from 1,066 randomized patients at baseline. Susceptibility was determined by broth microdilution. The most commonly isolated Gram-negative, Gram-positive, and anaerobic pathogens were Escherichia coli (n = 549), Streptococcus anginosus (n = 130), and Bacteroides fragilis (n = 96), respectively. Ceftazidime-avibactam was highly active against isolates of Enterobacteriaceae, with an overall MIC90 of 0.25 mg/liter. In contrast, the MIC90 for ceftazidime alone was 32 mg/liter. The MIC90 value for ceftazidime-avibactam (4 mg/liter) was one dilution lower than that of ceftazidime alone (8 mg/liter) against isolates of Pseudomonas aeruginosa The ceftazidime-avibactam MIC90 for 109 ceftazidime-nonsusceptible Enterobacteriaceae isolates was 2 mg/liter, and the MIC range for 6 ceftazidime-nonsusceptible P. aeruginosa isolates was 8 to 32 mg/liter. The MIC90 values were within the range of susceptibility for the study drugs permitted per the protocol in the phase 3 study to provide coverage for aerobic Gram-positive and anaerobic pathogens. These findings demonstrate the in vitro activity of ceftazidime-avibactam against bacterial pathogens commonly observed in cIAI patients, including ceftazidime-nonsusceptible Enterobacteriaceae (This study has been registered at ClinicalTrials.gov under identifier NCT01499290.).


Subject(s)
Anti-Bacterial Agents/pharmacology , Azabicyclo Compounds/pharmacology , Ceftazidime/pharmacology , Intraabdominal Infections/microbiology , Bacteroides fragilis/drug effects , Double-Blind Method , Drug Combinations , Escherichia coli/drug effects , Humans , Microbial Sensitivity Tests , Pseudomonas aeruginosa/drug effects , Streptococcus anginosus/drug effects
10.
Int J Antimicrob Agents ; 51(2): 227-234, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28705666

ABSTRACT

To evaluate the activity of ceftolozane/tazobactam compared with other broad-spectrum antimicrobials against Pseudomonas aeruginosa and Enterobacteriaceae, 497 non-duplicate P. aeruginosa and 802 Enterobacteriaceae clinical isolates were consecutively collected during the period from September 2014 to April 2015 from patients in Germany with bloodstream, lower respiratory tract, intra-abdominal or urinary tract infections. Antimicrobial susceptibility testing was performed by broth microdilution. Results were interpreted according to EUCAST criteria. Ceftolozane/tazobactam showed good activity against Escherichia coli and Klebsiella pneumoniae isolates with MIC50/90 values of 0.25/0.5 mg/L and 0.25/1 mg/L, respectively. Comparatively, piperacillin/tazobactam, ceftazidime and meropenem MIC50/90 values were 2/8 mg/L, 0.25/8 mg/L and ≤0.03/ ≤ 0.03 mg/L, respectively, for E. coli, and 2/16 mg/L, 0.12/8 mg/L, and ≤0.03/ ≤ 0.03 mg/L, respectively, for K. pneumoniae isolates. The activity of ceftolozane/tazobactam against P. aeruginosa was superior to that of other antipseudomonal antimicrobials. Based on MIC50/90 values, ceftolozane/tazobactam (0.5/2 mg/L) was more active than piperacillin/tazobactam (8/64 mg/L), ceftazidime (2/16 mg/L), cefepime (2/16 mg/L) or meropenem (0.5/8 mg/L). In conclusion, ceftolozane/tazobactam exhibited the best in vitro potency of the antibiotics tested against P. aeruginosa, including isolates that were resistant to piperacillin/tazobactam, cefepime, ceftazidime, doripenem, meropenem, ciprofloxacin, levofloxacin, amikacin, and tobramycin. Ceftolozane/tazobactam has the potential to become a useful addition to the limited armamentarium of drugs that can be used to treat this problem pathogen.


Subject(s)
Anti-Infective Agents, Urinary/therapeutic use , Cephalosporins/therapeutic use , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae/drug effects , Penicillanic Acid/analogs & derivatives , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/drug effects , Urinary Tract Infections/drug therapy , Drug Resistance, Multiple, Bacterial , Enterobacteriaceae/isolation & purification , Enterobacteriaceae Infections/microbiology , Germany , Humans , Microbial Sensitivity Tests , Penicillanic Acid/therapeutic use , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/isolation & purification , Tazobactam , Urinary Tract Infections/microbiology
11.
Int J Antimicrob Agents ; 47(3): 210-6, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26899413

ABSTRACT

Complicated intra-abdominal infection (cIAIs) are a common and important cause of morbidity worldwide. In this study, the clinical features, microbiological profiles, antimicrobial patterns and treatments of 3233 cIAI patients (mean age, 47.6 years; 54.7% male) with 3531 hospitalisations from 2008-2013 were retrospectively investigated. The most commonly isolated bacteria were Escherichia coli (47.6%), Klebsiella pneumoniae (16.9%), Enterococcus faecalis (10.4%) and Pseudomonas aeruginosa (8.8%). Ciprofloxacin, aminoglycoside (gentamicin), piperacillin/tazobactam and carbapenems exhibited activity against 53%, 76%, 88% and 100% of extended-spectrum ß-lactamase (ESBL)-positive Enterobacteriaceae isolates, respectively. Pseudomonas aeruginosa isolates exhibited 100%, 95%, 88%, 71% and 76% susceptibility to aminoglycoside (gentamicin), ciprofloxacin, meropenem, imipenem and ceftazidime, respectively, and Enterococcus remained 100% susceptible to vancomycin and linezolid. ß-Lactam antibacterials other than penicillin (specifically third-generation cephalosporins) and imidazole derivatives (ornidazole and metronidazole) were the most common first-line treatments. Patients subjected to regimen change after initial antibiotic treatment had predisposing conditions (e.g. older age, more severe co-morbidities) and a higher incidence of P. aeruginosa infection; in addition, these patients encountered a higher average cost of care and worse clinical outcomes compared with those without medication modification. Taken together, these findings indicate the importance of appropriate initial empirical therapy and suggest the use of combination therapy comprising cephalosporins and metronidazole.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Epidemiologic Studies , Intraabdominal Infections , Carbapenems/therapeutic use , China/epidemiology , Ciprofloxacin/therapeutic use , Drug Resistance, Multiple, Bacterial , Drug Therapy, Combination , Enterococcus faecalis/drug effects , Escherichia coli/drug effects , Female , Gentamicins/therapeutic use , Humans , Intraabdominal Infections/drug therapy , Intraabdominal Infections/epidemiology , Intraabdominal Infections/microbiology , Klebsiella pneumoniae/drug effects , Male , Microbial Sensitivity Tests , Middle Aged , Penicillanic Acid/analogs & derivatives , Penicillanic Acid/therapeutic use , Piperacillin/therapeutic use , Pseudomonas aeruginosa/drug effects , Tazobactam , Treatment Outcome
12.
J Chemother ; 27(2): 67-73, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24548089

ABSTRACT

The study for monitoring antimicrobial resistance trends (SMART) surveillance program monitors the epidemiology and trends in antibiotic resistance of intra-abdominal pathogens to currently used therapies. The current report describes such trends during 2010-2011. A total of 25,746 Gram-negative clinical isolates from intra-abdominal infections were collected and classified as hospital-associated (HA) if the hospital length of stay (LOS) at the time of specimen collection was ≥48 hours, community-associated (CA) if LOS at the time of specimen collection was <48 hours, or unknown (no designation given by participating centre). A total of 92 different species were collected of which the most common was Escherichia coli: 39% of all isolates in North America to 55% in Africa. Klebsiella pneumoniae was the second most common pathogen: 11% of all isolates from Europe to 19% of all isolates from Asia. Isolates were from multiple intra-abdominal sources of which 32% were peritoneal fluid, 20% were intra-abdominal abscesses, and 16.5% were gall bladder infections. Isolates were further classified as HA (55% of all isolates), CA (39% of all isolates), or unknown (6% of all isolates). The most active antibiotics tested were imipenem, ertapenem, amikacin, and piperacillin-tazobactam. Resistance rates to all other antibiotics tested were high. Considering the current data set and high-level resistance of intra-abdominal pathogens to various antibiotics, further monitoring of the epidemiology of intra-abdominal infections and their susceptibility to antibiotics through SMART is warranted.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial , Global Health , Gram-Negative Aerobic Bacteria/drug effects , Gram-Negative Bacterial Infections/drug therapy , Intraabdominal Infections/drug therapy , Abdominal Abscess/drug therapy , Abdominal Abscess/epidemiology , Abdominal Abscess/microbiology , Anti-Bacterial Agents/pharmacology , Ascitic Fluid/microbiology , Cholecystitis/drug therapy , Cholecystitis/epidemiology , Cholecystitis/microbiology , Cross Infection/drug therapy , Cross Infection/epidemiology , Cross Infection/microbiology , Drug Resistance, Multiple, Bacterial , Epidemiological Monitoring , Escherichia coli/drug effects , Escherichia coli/growth & development , Escherichia coli/isolation & purification , Escherichia coli Infections/drug therapy , Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Gram-Negative Aerobic Bacteria/growth & development , Gram-Negative Aerobic Bacteria/isolation & purification , Gram-Negative Bacterial Infections/epidemiology , Gram-Negative Bacterial Infections/microbiology , Humans , Incidence , Intraabdominal Infections/epidemiology , Intraabdominal Infections/microbiology , Klebsiella Infections/drug therapy , Klebsiella Infections/epidemiology , Klebsiella Infections/microbiology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/growth & development , Klebsiella pneumoniae/isolation & purification , Length of Stay , Microbial Sensitivity Tests
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