Pre-clinical impact of the synergistic mechanism of daptomycin and ceftaroline in patients with methicillin-resistant Staphylococcus aureus bacteremia infections

2021 ◽  
Vol 15 ◽  
Author(s):  
Jennyflore Eliazar ◽  
Tevin Johnson ◽  
Christiane Chbib
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Clinical Impact ◽  
In Vitro Studies ◽  
Methicillin Resistant ◽  
Colony Forming Unit ◽  
Staphylococcus Aureus Bacteremia ◽  
Synergistic Mechanism

Background: Our study aims at assessing the pre-clinical impact of the synergistic mechanism of Daptomycin (DAP) and Ceftaroline (CFT) in patients with Methicillin-resistant Staphylococcus aureus bacteremia infections (MRSAB). Methods: A systematic overview was conducted by searching PubMed, Oxford academic, and Cochrane library up to June 2020. Study selection and data extraction: All English- language clinical trials, in vitro studies, and case reports related to the synergistic drug therapy for MRSAB. Results: In the case of MRSAB infections, we examined two different in vitro studies that showed effective synergism with DAP and CFT. The minimum inhibitory concentration (MIC) range observed for each is as follow: DAP 0.125-1 mg/L, CFT 0.38-1 mg/L, DAP + CFT 0.094-0.5 mg/L, vancomycin (VAN) 0.75-2 mg/L, VAN + CFT 0.25-2 mg/L. DAP + CFT combination displayed the most efficacy with the lowest MIC. The statistical analysis performed showed that DAP + CFT obtained significantly lower fractional inhibitory concentration (FIC) values (0.941 ± 0.328) compared with VAN + CFT. In vitro activities of regimens tested on DAP non-susceptibility and VAN intermediate after 96 hours showed DAP 8.29 ± 0.03a log10 CFU/mL, VAN 6.82 ± 0.04a log10 Colony Forming Unit (CFU)/mL, CFT 4.63 ± 0.19a log10 CFU/mL, DAP + CFT 1.15 ± 0.20b log10 CFU/mL, VAN + CFT 3.18 ± 0.49a log10 CFU/mL. ( a meaning significantly different than DAP plus CFT, P< equal to 0.001b meaning therapeutic enhancement combination was defined as ≥ 2 log10 CFU/ml reduction over the most active single agent). Based on these results, although DAP was not susceptible, the colony forming unit (CFU) for DAP and CFT had the best therapeutic results. Conclusion: In vitro studies have shown that combination DAP and CFT is more efficacious than the combination on VAN and CFT in MRSA bacteremia infections. The synergic effects of DAP (bactericidal) and CFT (bactericidal) is statistically significant, in recent trials, warranting promising evidence for its use in complicated bacteremia infection.

scholarly journals Adjunctive ceftaroline in combination with daptomycin or vancomycin for complicated methicillin-resistant Staphylococcus aureus bacteremia after monotherapy failure

2019 ◽  
Vol 6 ◽  
pp. 204993611988650 ◽  
Author(s):  
Joseph Patrik Hornak ◽  
Seher Anjum ◽  
David Reynoso
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Treatment Options ◽  
Source Control ◽  
Optimal Timing ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
Persistent Bacteremia

Background: Methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) may fail to improve with standard monotherapy, particularly in patients with multifocal infection, incomplete source control, or persistent bacteremia. Synergy observed in vitro between ceftaroline (CPT) and daptomycin (DAP) or vancomycin (VAN) may translate into clinical benefit. Here, we describe our experience with DAP/CPT and VAN/CPT for complicated MRSA-B after monotherapy failure. Methods: Single-center, retrospective review of consecutive patients treated with DAP/CPT or VAN/CPT for MRSA-B after monotherapy failure from 1 January 2016 to 30 November 2018. Results: We identified 11 instances of combination therapy in 10 patients (DAP/CPT = 6, VAN/CPT = 5) with 1 patient receiving VAN/CPT followed by DAP/CPT. Rates of multifocal infection, incomplete source control, persistent bacteremia, and infective endocarditis were high (100%, 80%, 60%, and 60%, respectively). Combination therapy was initiated most commonly for persistent bacteremia (60%). When patients were persistently bacteremic, median preceding duration was 13 days and median time to clearance was 3 days. Total microbiologic cure rate was 100%. There were zero instances of bacteremia relapse at 30 days (30D) or 60 days (60D). All-cause 30D and 60D mortality rates were 11.1% and 33.3%, respectively. Conclusions: Combination therapy demonstrated success in diverse cases of refractory MRSA-B, including instances of persistent bacteremia paired with incomplete source control. Optimal timing and therapeutic cadence for combination therapy remain unclear. Our findings suggest that DAP/CPT and VAN/CPT can be considered for complicated MRSA bacteremia when other treatment options fail or are unavailable. We propose persistent bacteremia with incomplete source control to be a clinical niche particularly worthy of further investigation.

scholarly journals Effects of Sauropus androgynus extract and its combination with ampicillin against Methicillin-resistant Staphylococcus aureus: An in vitro study

2020 ◽  
Vol 6 (2) ◽  
pp. 128-133
Author(s):  
Asih Rahayu ◽  
Chylen Setiyo Rini ◽  
Yos Adi Prakoso ◽  
Bagus Uda Palgunadi ◽  
Muhammad Aris Munandar
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Synergistic Effects ◽  
In Vitro Study ◽  
Latex Agglutination ◽  
Herbal Extract ◽  
Ultrastructural Changes ◽  
Methicillin Resistant

Background and Aim: The massive utilization of antibiotics has increased resistant genes produced by bacteria. Many bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA), have become resistant against ampicillin (AMP). The combination of an herbal extract with AMP is expected to generate synergistic effects and may restore the susceptibility of MRSA against AMP. This study aimed to analyze the potency of Sauropus androgynous extract (SAE) as a single extract and combination with AMP against MRSA. Materials and Methods: Sauropus androgynous was extracted using 60% ethanol. SAE biochemical compounds were analyzed qualitatively and quantitatively. SAE, AMP, and SAE+AMP were tested against MRSA isolates to determine the minimum inhibitory concentration and fractional inhibitory concentration. The inhibition of penicillin-binding proteins 2a (PBP2a) was analyzed using a latex agglutination test. Further, the disruptive membrane effects of SAE, AMP, and SAE+AMP were analyzed using a scanning electron microscope. The analysis of data was conducted using SPSS version 16 with p=0.01. Results: SAE contained bioactive compounds such as phenolics and flavonoids. Further, 2 mg/mL of SAE could be used as the potential concentration against MRSA isolates in vitro. In addition, the utilization of SAE+AMP generated synergistic effects, restored the susceptibility of isolates against AMP, decreased the synthesis of PBP2a by the MRSA, and induced ultrastructural changes in the bacterial membrane. Conclusion: This study indicated that the utilization of SAE potentially inhibits the growth of MRSA through decreasing of PBP2a expression, disruption of the MRSA membrane, while the combination of SAE+AMP showed synergistic effects against MRSA.

Diminished Susceptibility to Daptomycin Accompanied by Clinical Failure in a Patient With Methicillin-Resistant Staphylococcus aureus Bacteremia

2006 ◽  
Vol 27 (3) ◽  
pp. 315-317 ◽  
Author(s):  
David Hirschwerk ◽  
Christine C. Ginocchio ◽  
Maureen Bythrow ◽  
Susan Condon
Keyword(s):  
Staphylococcus Aureus ◽  
Minimum Inhibitory Concentration ◽  
Dna Fingerprinting ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Clinical Failure ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
New Information ◽  
Serious Infections

We cared for a patient with methicillin-resistant Staphylococcus aureus bacteremia who experienced clinical failure with daptomycin. The failure was accompanied by progressive elevation of the daptomycin minimum inhibitory concentration during treatment. DNA fingerprinting confirmed that the minimum inhibitory concentration elevation occurred within the same strain of methicillin-resistant Staphylococcus aureus. This observation provides important new information to clinicians who adopt this promising drug for treatment of serious infections caused by methicillin-resistant Staphylococcus aureus.

scholarly journals NONANTIBIOTICS ENHANCE THE ANTIBACTERIAL ACTIVITY OF CEFTRIAXONE AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS

2018 ◽  
Vol 11 (11) ◽  
pp. 134
Author(s):  
Akilandeswari Krishnan ◽  
Ruckmani Kandasamy
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Dilution Method ◽  
Methicillin Resistant ◽  
Therapeutic Procedures ◽  
Mebeverine Hydrochloride ◽  
Lactam Antibiotic ◽  
Antiulcer Drugs

Objectives: Antibiotic resistance is one of the most persistent issues worldwide nowadays, and methicillin-resistant Staphylococcus aureus (MRSA) infection is one such issue where the standard therapeutic procedures involving powerful antibiotics have failed in controlling the infection.Methods: In the present study, the antibacterial potency of the nonantibiotics troxipide (TR), mebeverine hydrochloride (Hcl), and their combinations with ceftriaxone (CEF) against MRSA has been investigated using microbiological assays of microplate dilution method and combination index interpretations of the nonantibiotics with β-lactam antibiotic CEF and the zone of inhibition method.Results: The nonantibiotics ME and TR inhibited resistant strain tested in vitro in the checkerboard assay, where the results showed that CEF and TR exhibited minimum inhibitory concentration (MIC) at concentrations of 50 μg/ml and 318 μg/ml, respectively. Interestingly, CEF when combined with TR reduced the MIC to 8 μg/ml and 78 μg/ml. According to the results, CEF with TR exhibited synergistic interactions at the fractional inhibitory concentration of 0.36–1.4. ME and TR and its combinations, CEF with ME, and CEF with TR have considerable anti-MRSA efficacy, with synergism though at 36 h of incubation.Conclusion: ME and TR being antispasmodic and antiulcer drugs can also be used against MRSA infections, which could prove to be favorable in the reduction of dosage of antibiotics such as CEF, and cutting down the need for additional administration of antibiotics to the patients affected with multiple complications such as gastrointestinal ulcer, spasm difficulties, and infection.

scholarly journals Antimicrobial activity of SM-17466, a novel carbapenem antibiotic with potent activity against methicillin-resistant Staphylococcus aureus.

1995 ◽  
Vol 39 (4) ◽  
pp. 910-916 ◽  
Author(s):  
Y Sumita ◽  
H Nouda ◽  
K Kanazawa ◽  
M Fukasawa
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Antibacterial Activities ◽  
Infection Model ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Wide Range

The in vitro and in vivo antibacterial activities of SM-17466, a new 1 beta-methyl carbapenem, were evaluated against a wide range of clinical bacterial isoaltes and compared with the activities of meropenem, imipenem, vancomycin, and arbekacin. SM-17466 had a broad spectrum of action against gram-positive bacteria, showing especially potent activity against methicillin-resistant staphylococci. The MICs of SM-17466, meropenem, imipenem, vancomycin, and arbekacin at which 90% of clinical isolates of methicillin-resistant Staphylococcus aureus were inhibited were 3.13, 50, 100, 1.56, and 3.13 micrograms/ml, respectively. This activity of SM-17466 was almost equivalent to those of the antibiotics used for the treatment of infections caused by this organism. SM-17466 also showed bactericidal activity against methicillin-resistant S. aureus. In contrast, SM-17466 was less active against gram-negative bacteria, especially against Pseudomonas aeruginosa, compared with the other carbapenems; however, of the carbapenems, SM-17466 exhibited the highest activity against Haemophilus influenzae and Bacteriodes fragilis. SM-17466, at a 50% inhibitory concentration of less than 1 microgram/ml, bound to penicillin-binding proteins 1 to 4 in methicillin-susceptible S. aureus and also had good binding to penicillin-binding protein 2' in a methicillin-resistant strain (50% inhibitory concentration, 5.9 micrograms/ml). This high affinity, which was 10 and 20 times greater than those for meropenem and imipenem, respectively, was reflected in the potent activity of SM-17466 against methicillin-resistant S. aureus. SM-17466 demonstrated excellent in vivo efficacy against methicillin-susceptible and -resistant S. aureus strains in a mouse peritoneal infection model: the efficacy of SM-17466 against methicillin-resistant strains was equal to or one-third that of vancomycin. This activity was comparable to the in vitro activity of SM-17466. The subcutaneous injection of SM-17466 in mice revealed that the half-life of SM-17466 in serum was about 18 min, intermediate between those of vancomycin and arbekacin and 1.5-fold that of imipenem-cilastatin. SM-17466 was resistant to hydrolysis by swine renal dehydropeptidase I, to an extent comparable to the resistance shown by meropenem.

Sign in / Sign up

Export Citation Format

Share Document