Novel pharmacotherapy for the treatment of hospital-acquired and ventilator-associated pneumonia caused by resistant gram-negative bacteria

2018 ◽  
Vol 19 (4) ◽  
pp. 397-408 ◽  
Author(s):  
James M. Kidd ◽  
Joseph L. Kuti ◽  
David P. Nicolau
2008 ◽  
Vol 52 (12) ◽  
pp. 4388-4399 ◽  
Author(s):  
Chris M. Pillar ◽  
Mohana K. Torres ◽  
Nina P. Brown ◽  
Dineshchandra Shah ◽  
Daniel F. Sahm

ABSTRACT Doripenem, a 1β-methylcarbapenem, is a broad-spectrum antibiotic approved for the treatment of complicated urinary tract and complicated intra-abdominal infections. An indication for hospital-acquired pneumonia including ventilator-associated pneumonia is pending. The current study examined the activity of doripenem against recent clinical isolates for the purposes of its ongoing clinical development and future longitudinal analysis. Doripenem and comparators were tested against 12,581 U.S. clinical isolates collected between 2005 and 2006 including isolates of Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pneumoniae, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. MICs (μg/ml) were established by broth microdilution. By MIC90, doripenem was comparable to imipenem and meropenem in activity against S. aureus (methicillin susceptible, 0.06; resistant, 8) and S. pneumoniae (penicillin susceptible, ≤0.015; resistant, 1). Against ceftazidime-susceptible Enterobacteriaceae, the MIC90 of doripenem (0.12) was comparable to that of meropenem (0.12) and superior to that of imipenem (2), though susceptibility of isolates exceeded 99% for all evaluated carbapenems. The activity of doripenem was not notably altered against ceftazidime-nonsusceptible or extended-spectrum β-lactamase screen-positive Enterobacteriaceae. Doripenem was the most potent carbapenem tested against P. aeruginosa (MIC90/% susceptibility [%S]: ceftazidime susceptible = 2/92%S, nonsusceptible = 16/61%S; imipenem susceptible = 1/98.5%S, nonsusceptible = 8/56%S). Against imipenem-susceptible Acinetobacter spp., doripenem (MIC90 = 2, 89.1%S) was twice as active by MIC90 as were imipenem and meropenem. Overall, doripenem potency was comparable to those of meropenem and imipenem against gram-positive cocci and doripenem was equal or superior in activity to meropenem and imipenem against Enterobacteriaceae, including β-lactam-nonsusceptible isolates. Doripenem was the most active carbapenem tested against P. aeruginosa regardless of β-lactam resistance.


Author(s):  
Adeniyi J. Idigo ◽  
Matthew L. Brown ◽  
Howard W. Wiener ◽  
Russell L. Griffin ◽  
Yuanfan Ye ◽  
...  

Abstract Objective: We observed an overall increase in the use of third- and fourth-generation cephalosporins after fluoroquinolone preauthorization was implemented. We examined the change in specific third- and fourth-generation cephalosporin use, and we sought to determine whether there was a consequent change in non-susceptibility of select Gram-negative bacterial isolates to these antibiotics. Design: Retrospective quasi-experimental study. Setting: Academic hospital. Intervention: Fluoroquinolone preauthorization was implemented in the hospital in October 2005. We used interrupted time series (ITS) Poisson regression models to examine trends in monthly rates of ceftriaxone, ceftazidime, and cefepime use and trends in yearly rates of nonsusceptible isolates (NSIs) of select Gram-negative bacteria before (1998–2004) and after (2006–2016) fluoroquinolone preauthorization was implemented. Results: Rates of use of ceftriaxone and cefepime increased after fluoroquinolone preauthorization was implemented (ceftriaxone RR, 1.002; 95% CI, 1.002–1.003; P < .0001; cefepime RR, 1.003; 95% CI, 1.001–1.004; P = .0006), but ceftazidime use continued to decline (RR, 0.991, 95% CI, 0.990–0.992; P < .0001). Rates of ceftazidime and cefepime NSIs of Pseudomonas aeruginosa (ceftazidime RR, 0.937; 95% CI, 0.910–0.965, P < .0001; cefepime RR, 0.937; 95% CI, 0.912–0.963; P < .0001) declined after fluoroquinolone preauthorization was implemented. Rates of ceftazidime and cefepime NSIs of Enterobacter cloacae (ceftazidime RR, 1.116; 95% CI, 1.078–1.154; P < .0001; cefepime RR, 1.198; 95% CI, 1.112–1.291; P < .0001) and cefepime NSI of Acinetobacter baumannii (RR, 1.169; 95% CI, 1.081–1.263; P < .0001) were increasing before fluoroquinolone preauthorization was implemented but became stable thereafter: E. cloacae (ceftazidime RR, 0.987; 95% CI, 0.948–1.028; P = .531; cefepime RR, 0.990; 95% CI, 0.962–1.018; P = .461) and A. baumannii (cefepime RR, 0.972; 95% CI, 0.939–1.006; P = .100). Conclusions: Fluoroquinolone preauthorization may increase use of unrestricted third- and fourth-generation cephalosporins; however, we did not observe increased antimicrobial resistance to these agents, especially among clinically important Gram-negative bacteria known for hospital-acquired infections.


2019 ◽  
Vol 12 (5) ◽  
pp. 630-633 ◽  
Author(s):  
Ding-Yun Feng ◽  
Yu-Qi Zhou ◽  
Xiao-Ling Zou ◽  
Mi Zhou ◽  
Wen-Bin Wu ◽  
...  

2020 ◽  
Vol 8 (8) ◽  
pp. 2111-2119 ◽  
Author(s):  
Jea Sung Ryu ◽  
San Hae Im ◽  
Yoo Kyung Kang ◽  
Yang Soo Kim ◽  
Hyun Jung Chung

A rapid and universal assay for detection of Gram-negative bacteria was developed using a fluorescent derivative of colistin. Labeling is achieved within 10 min in various bacteria relevant to hospital-acquired infections in complex samples.


2007 ◽  
Vol 28 (7) ◽  
pp. 825-831 ◽  
Author(s):  
David J. Weber ◽  
William A. Rutala ◽  
Emily E. Sickbert-Bennett ◽  
Gregory P. Samsa ◽  
Vickie Brown ◽  
...  

Objective.Nosocomial pneumonia is the leading cause of mortality attributed to nosocomial infection. Appropriate empirical therapy has been associated with improved survival, but data are limited regarding the etiologic agents of hospital-acquired pneumonia in non-ventilated patients (HAP). This evaluation assessed whether the currently recommended empirical therapy is appropriate for both ventilator-associated pneumonia (VAP) and HAP by evaluating the infecting flora.Design.Prospectively collected hospitalwide surveillance data was obtained by infection control professionals using standard Centers for Disease Control and Prevention definitions.Setting.A tertiary care academic hospital.Patients.All patients admitted from 2000 through 2003.Results.A total of 588 episodes of pneumonia were reported in 556 patients: 327 episodes of VAP in 309 patients, and 261 episodes of HAP in 247 Patients. The infecting flora in ventilated patients included gram-positive cocci (32.0% [oxacillin-susceptible Staphylococcus aureus {OSSA}, 9.25%; oxacillin-resistant Staphylococcus aureus {ORSA}, 17.75%]), gram-negative bacilli (59.0% {Pseudomonas aeruginosa, 17.50%; Stenotrophomonas maltophilia, 6.75%; Acinetobacter species, 7.75%), and miscellaneous pathogens (9.0%). The infecting flora in nonventilated patients included gram-positive cocci (42.59% [OSSA, 13.33%; ORSA, 20.37%]), gram-negative bacilli (39.63% [P. aeruginosa, 9.26%; S. maltophilia, 1.11%; Acinetobacter species, 3.33%), and miscellaneous pathogens (17.78%).Conclusions.Our data demonstrated that patients with HAP, compared with those with VAP, had a similar frequency of infection with ORSA but less commonly had infections due to P. aeruginosa, Acinetobacter species, and S. maltophilia. However, the overall frequency of infection with these pathogens was sufficiently high to warrant the use of empirical therapy likely to be active against them. Our data supports using the currently recommended empirical therapy for both HAP and VAP.


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