scholarly journals Erratum to: Education: The role of the first siderophore cephalosporin Fetcroja® (cefiderocol) in UK clinical practice: introduction; Education: An introduction to the core data for cefiderocol with reflections for a possible role within UK clinical practice; Education: A compassionate use of cefiderocol to treat osteomyelitis caused by an XDR Pseudomonas aeruginosa; Compassionate use of cefiderocol for carbapenem-resistant Acinetobacter baumannii prosthetic joint infection; Education: An overview from the author of ‘Cefiderocol as rescue therapy for Acinetobacter baumannii and other carbapenem-resistant Gram-negative infections in intensive care unit patients’

2021 ◽  
Vol 3 (3) ◽  
Keyword(s):  
Clinical Practice ◽  
Acinetobacter Baumannii ◽  
Rescue Therapy ◽  
Joint Infection ◽  
Compassionate Use ◽  
Gram Negative ◽  
The Core ◽  
Carbapenem Resistant ◽  
Prosthetic Joint

scholarly journals The H-NS regulator plays a role in the stress induced by carbapenemase expression in Acinetobacter baumannii

2020 ◽  
Author(s):  
Fanny Huang ◽  
Noelle Fitchett ◽  
Chelsea Razo-Gutierrez ◽  
Casin Le ◽  
Grace Ra ◽  
...  
Keyword(s):  
Stress Response ◽  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Gram Negative ◽  
Toxic Species ◽  
Carbapenem Resistant ◽  
Dna Damaging Agents ◽  
Envelope Stress ◽  
Evolutionary Advantage

AbstractDisruption of the histone-like nucleoid structuring protein (H-NS) was shown to affect the ability for Gram-negative bacteria to regulate genes associated with virulence, persistence, stress response, quorum sensing, biosynthesis pathways and cell adhesion. Here, we used the expression of metallo-β-lactamases (MBLs) known to elicit envelope stress by the accumulation of toxic species in the periplasm to interrogate the role of H-NS in Acinetobacter baumannii, together with other stressors. Using a multidrug-resistant A. baumannii, we observed that H-NS plays a role in alleviating the stress triggered by MBL toxic precursors and counteract the effect of DNA-damaging agents, supporting its role in stress response.ImportanceCarbapenem-resistant A. baumannii (CRAB) is recognized as one of the most threatening gram-negative bacilli. H-NS is known to play a role in controlling the transcription of a variety of different genes, including those associated with stress response, persistence and virulence. In the present work, we uncovered a link between the role of H-NS in the A. baumannii stress response and its relationship with the envelope stress response and resistance to DNA-damaging agents. Overall, we posit a new role of H-NS, showing that H-NS serves to endure envelope stress that could also be a mechanism that alleviates the stress induced by MBL expression in A. baumannii. This could be an evolutionary advantage to further resist the action of carbapenems.

Cefiderocol as Rescue Therapy for Acinetobacter baumannii and Other Carbapenem-resistant Gram-negative Infections in Intensive Care Unit Patients

2020 ◽  
Author(s):  
Marco Falcone ◽  
Giusy Tiseo ◽  
Manuela Nicastro ◽  
Alessandro Leonildi ◽  
Alessandra Vecchione ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Stenotrophomonas Maltophilia ◽  
Inhibitory Concentration ◽  
Clinical Success ◽  
Rescue Therapy ◽  
Survival Rates ◽  
New Delhi ◽  
Ventilator Associated Pneumonia ◽  
Gram Negative ◽  
Carbapenem Resistant

Abstract Ten critically ill patients with either bacteremia or ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii, Stenotrophomonas maltophilia, or New Delhi metallo-β-lactamase–producing Klebsiella pneumoniae received cefiderocol. All strains had minimum inhibitory concentration ≤2 μg/mL. Thirty-day clinical success and survival rates were 70% and 90%, respectively. Two patients had a microbiological failure. Future prospective studies are warranted.

scholarly journals 1297. In-Vitro Antibacterial Activities of Cefiderocol (S-649266) Alone and With the Addition of Beta-Lactamase Inhibitors Against Multidrug-resistant Acinetobacter baumannii

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S663-S663
Author(s):  
Jacinda C Abdul-Mutakabbir ◽  
Logan Nguyen ◽  
Philip Maassen ◽  
Kyle Stamper ◽  
Razieh Kebriaei ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Beta Lactamase ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Mueller Hinton ◽  
Fold Reduction

Abstract Background Multidrug-resistant (MDR) infections caused by Acinetobacter baumannii continue to pose a serious public health threat. Cefiderocol (CFDC) is a new parental siderophore cephalosporin that has displayed potent activity against Gram-negative bacteria, more specifically non-fermenting Gram-negative bacilli, including A. baumannii. Although uncommon, elevated minimum inhibitory concentrations (MICs) to CFDC have been reported, when tested against A. baumannii isolates, in-vitro. The addition of beta-lactamase inhibitors has been shown to be successful in decreasing elevated CFDC MICs. The evaluation of sulbactam (SUL), tazobactam (TAZO), or clavulanic acid (CLAV) in addition to CFDC against A. baumannii isolates with elevated CFDC MICs, has yet to be reported. The objective of this study was to evaluate the activity of several beta-lactamase inhibitors in combination with CFDC against A. baumannii strains with high CFDC MICs. Methods One hundred and fifty carbapenem-resistant A. baumannii strains were selected from the Anti-infective Research Laboratory. MIC susceptibility testing was performed for all of the strains via broth microdilution (BMD). Seven strains that exhibited elevated CFDC MICs,16-32 mg/L, were assessed via BMD, with the addition of the following beta-lactamase inhibitors: TAZO, SUL, AVI, and CLAV to CFDC. All in-vitro testing for CFDC was completed with the use of iron-depleted cation-adjusted Mueller-Hinton broth to ensure the induction of bacterial iron transporters per manufacturer standards. Results A decline in elevated CFDC MIC values was observed in six of the seven A. baumannii strains, with the addition of each beta-lactamase inhibitor. AVI showed the most potent activity when added to CFDC, with an average 28- fold reduction in MIC values observed. SUL and CLAV produced similar fold reductions in the MIC values with an average 20-fold reduction observed with the addition of either agent to FDC. The addition of TAZO to CFDC also presented with a decline in MIC values, with an average 7-fold-reduction observed. Cefiderocol (CFDC) strains with MICs of 16-32 mg/l plus Beta-Lactamase Inhibitors Conclusion The addition of several beta-lactamase inhibitors to CFDC has shown promise in decreasing elevated CFDC MICs. Further research is warranted to determine the role of BLIs on CFDC activity. Disclosures Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)

scholarly journals The H-NS Regulator Plays a Role in the Stress Induced by Carbapenemase Expression in Acinetobacter baumannii

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Fanny Huang ◽  
Noelle Fitchett ◽  
Chelsea Razo-Gutierrez ◽  
Casin Le ◽  
Jasmine Martinez ◽  
...  
Keyword(s):  
Stress Response ◽  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Dna Damaging Agents ◽  
Envelope Stress ◽  
Evolutionary Advantage

ABSTRACT Disruption of the histone-like nucleoid structuring protein (H-NS) was shown to affect the ability of Gram-negative bacteria to regulate genes associated with virulence, persistence, stress response, quorum sensing, biosynthesis pathways, and cell adhesion. Here, we used the expression of metallo-β-lactamases (MBLs), known to elicit envelope stress by the accumulation of toxic precursors in the periplasm, to interrogate the role of H-NS in Acinetobacter baumannii, together with other stressors. Using a multidrug-resistant A. baumannii strain, we observed that H-NS plays a role in alleviating the stress triggered by MBL toxic precursors and counteracts the effect of DNA-damaging agents, supporting its role in stress response. IMPORTANCE Carbapenem-resistant A. baumannii (CRAB) is recognized as one of the most threatening Gram-negative bacilli. H-NS is known to play a role in controlling the transcription of a variety of different genes, including those associated with the stress response, persistence, and virulence. In the present work, we uncovered a link between the role of H-NS in the A. baumannii stress response and its relationship with the envelope stress response and resistance to DNA-damaging agents. Overall, we posit a new role of H-NS, showing that H-NS serves to endure envelope stress and could also be a mechanism that alleviates the stress induced by MBL expression in A. baumannii. This could be an evolutionary advantage to further resist the action of carbapenems.

scholarly journals Role of Universal 16S rRNA Gene PCR and Sequencing in Diagnosis of Prosthetic Joint Infection

2011 ◽  
Vol 50 (3) ◽  
pp. 583-589 ◽  
Author(s):  
M. Marin ◽  
J. M. Garcia-Lechuz ◽  
P. Alonso ◽  
M. Villanueva ◽  
L. Alcala ◽  
...  
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Rrna Gene ◽  
Prosthetic Joint

Role of tigecycline in the control of a carbapenem-resistant Acinetobacter baumannii outbreak in an intensive care unit

2009 ◽  
Vol 72 (3) ◽  
pp. 234-242 ◽  
Author(s):  
W. Jamal ◽  
M. Salama ◽  
N. Dehrab ◽  
G. Al Hashem ◽  
M. Shahin ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Acinetobacter Baumannii ◽  
Carbapenem Resistant

scholarly journals Efficacy of Colistin-Loaded Cement Spacer in Carbapenem-Resistant Klebsiella pneumoniae Experimental Prosthetic Joint Infection

2016 ◽  
Vol 3 (suppl_1) ◽  
Author(s):  
Laure Gatin ◽  
Azzam Saleh-Mghir ◽  
Frederic Laurent ◽  
Marie-Clémence Verdier ◽  
Idir Ghout ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Cement Spacer ◽  
Carbapenem Resistant ◽  
Prosthetic Joint

scholarly journals 392. Epidemiology and Treatment Outcome of Gram-Negative Polymicrobial, Gram-Positive Polymicrobial and Mixed Polymicrobial Prosthetic Joint Infection

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S202-S202 ◽  
Author(s):  
Babak Hooshmand ◽  
Dima Youssef ◽  
Kathleen M Riederer ◽  
Susan M Szpunar ◽  
Meredith M Coyle ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Joint Infection ◽  
Suppressive Therapy ◽  
Two Stage ◽  
Gram Positive ◽  
Gram Negative ◽  
Presenting Symptoms ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Prosthesis Removal

Abstract Background Polymicrobial prosthetic joint infections (PMPJIs) are rare but treatment is usually challenging. Published studies described the PMPJIs without differentiating the component pathogens. We assessed clinical features and treatment outcome among Gram-negative polymicrobial (GNPM), Gram-positive polymicrobial (GPPM) and mixed polymicrobial (MPM) PJIs. Methods A retrospective cohort was studied at three Ascension hospitals in Detroit from January 2012 to December 2018. Cases were identified using the International Classification of Diseases, 9th and 10th Revision code specific for PJIs. Patient’s electronic medical records were reviewed. Results 38 patients with PMPJI with a mean age of 67 years. were identified. 71% patients were female and caucasians. Nineteen (50%) patients had MPM, 16 (42%) had GPPM and 3 had GNPM. Among MPM PJIs, 14 (74%) involved hips, 4 (21%) knee and 1 (5%) ankle joint. Among GPPM PJIs, 7 (44%) involved hips, 8 (50%) knee and 1 (6%) shoulder joints. Among GNPM PJIs, 1 (33%) involved hip and 2 (67%) involved knee joints. 4 (21%), 1 (6%), and 1 (33%) patients had diabetes among MPM, GPPM and GNPM, respectively. Symptom onset of less than a week was noted in 13 (68%), 5 (31%), 3(100%) and of more than 3 weeks in 3 (16%), 7 (43%) and in 0 among MPM, GPPM and GNPM, respectively. 18 (95%), 12 (75%) and 2 (67%) patients presented with pain; 16 (84%), 6 (38%) and 3 (100%) patients had drainage among MPM, GPPM and GNPM, respectively. Among MPM PJIs, 12 (63%) underwent debridement, antibiotics and implant retention (DAIR), 2 (11%) for two stage exchange, 4 (21%) for chronic suppressive therapy and 1 (5%) had an amputation. 6 (58%) were readmitted within 6 months; 3 (50%) required prosthesis removal, 1 (4%) each died, was made hospice and was lost to follow-up. Among GPPM PJIs, 12 (75%) underwent DAIR and 4 (25%) went for two stage exchange. 9 (69%) patients among GPPM PJIs were readmitted in 6 months and 3 (50%) required prosthesis removal. All 3 of GNPM PJIs underwent DAIR and none were readmitted in 6 months. Conclusion Pain and drainage were common presenting symptoms. All GNPM PJIs presented within 1 week of symptoms and were treated successfully with DAIR. MPM and GPPM PJIs had high readmission rates and 6/26 (23%) managed with DAIR required prosthesis removal. Disclosures All authors: No reported disclosures.

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