Comparison of Levofloxacin, Alatrofloxacin, and Vancomycin for Prophylaxis and Treatment of Experimental Foreign-Body-Associated Infection by Methicillin-Resistant Staphylococcus aureus

ABSTRACT The prophylactic and therapeutic activities of two fluoroquinolones, levofloxacin and alatrofloxacin (the l-Ala-l-Ala prodrug of trovafloxacin), were compared to those of vancomycin in two different experimental models of foreign-body-associated infections caused by methicillin-resistant but quinolone-susceptible Staphylococcus aureus (MRSA) isolates. In a guinea pig model of prophylaxis, subcutaneously implanted tissue cages were infected with 103 CFU of MRSA, which was a 100% infectious dose in control animals. A single dose of 50 mg of levofloxacin per kg of body weight, administered intraperitoneally 3 h before bacterial challenge, was more efficient than vancomycin for the prevention of infections in tissue cages with MRSA inocula of 104 and 105 CFU. In a rat model used to evaluate therapy of chronic tissue cage infection caused by MRSA, the efficacies of 7-day high-dose regimens of levofloxacin (100 mg/kg once a day [q.d.] or 50 mg/kg twice a day [b.i.d.]) or alatrofloxacin (50 mg/kg q.d.) were compared to the efficacy of vancomycin (50 mg/kg b.i.d.). Active levels of levofloxacin, trovafloxacin, and vancomycin were continuously present in tissue cage fluid, with the levels exceeding the minimal bactericidal concentrations for MRSA during therapy. The q.d. and b.i.d. regimens of levofloxacin had equivalent activities and were significantly (P < 0.05) more active than alatrofloxacin or vancomycin in decreasing the viable counts of MRSA in tissue cage fluids. No quinolone-resistant mutants emerged during therapy with either fluoroquinolone. The mechanisms explaining the inferior activity of alatrofloxacin compared to the activity of levofloxacin against chronic foreign-body-associated infections by MRSA are unknown.

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MRSA REMAINS A GREAT PRIORITY DUE TO THE TREMENDOUS MORTALITY --- A BIRD'S EYE VIEW

10.36106/gjra/0811782 ◽

2021 ◽

pp. 114-118

Author(s):

Raghavendra Rao M. V ◽

Mubasheer Ali ◽

Yogendra Kumar Verma ◽

Dilip Mathai ◽

Tina Priscilla ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Drug Resistance ◽

Chronic Infection ◽

Methicillin Resistant Staphylococcus Aureus ◽

Multiple Drug Resistance ◽

Multiple Drug ◽

High Dose ◽

Benzyl Penicillin ◽

Methicillin Resistant ◽

Antimicrobial Sensitivity

Methicillin-resistant Staphylococcus aureus (MRSA) is difcult to treat with methicillin, amoxicillin, penicillin, oxacillin, and other commonly used antibiotics because of its resistance. Staphylococcus organisms rapidly develop drug resistance as many as 50% of the domiciliary and 80% of the hospital strains are now penicillin resistant. Staphylococcus aureus also show multiple drug resistance. Therefore, Staphylococcal isolates should always be tested for antimicrobial sensitivity and chronic infection should be treated by more than one drug. Before 1960,when methicillin, is the rst penicillin's-resistant penicillin's, was brought into use, about 1%of the strains of the Staphylococcus aureus were "methicillin resistant" and by 1970 in Britain their proportion has risen to about 5%.These strains are tolerant of, low therapeutic concentrations of methicillin, cloxacillin, benzyl penicillin and ampicillin.They do not destroy methicillin and cloxacillin, but most of them are penicillinase-producing as well as being "methicillin resistant" and therefore inactivate benzyl penicillin and ampicillin. Its resistance is uncertain since infections may be cured with a high dose of methicillin.

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Novel Use of Rifabutin and Rifapentine to Treat Methicillin-Resistant Staphylococcus aureus in a Rat Model of Foreign Body Osteomyelitis

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa401 ◽

2020 ◽

Vol 222 (9) ◽

pp. 1498-1504

Author(s):

Melissa J Karau ◽

Suzannah M Schmidt-Malan ◽

Mariana Albano ◽

Jayawant N Mandrekar ◽

Christina G Rivera ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Foreign Body ◽

Rat Model ◽

Methicillin Resistant Staphylococcus Aureus ◽

Joint Infection ◽

Kirschner Wire ◽

Methicillin Resistant ◽

Joint Infections ◽

Single Animal ◽

K Wires

Abstract Background Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. Methods Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. Results Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. Conclusions Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.

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Efficacy of tigecycline alone and with rifampin in foreign-body infection by methicillin-resistant Staphylococcus aureus

Journal of Infection ◽

10.1016/j.jinf.2011.07.001 ◽

2011 ◽

Vol 63 (3) ◽

pp. 229-235 ◽

Cited By ~ 8

Author(s):

C. Garrigós ◽

O. Murillo ◽

G. Euba ◽

R. Verdaguer ◽

F. Tubau ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Foreign Body ◽

Methicillin Resistant Staphylococcus Aureus ◽

Methicillin Resistant

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RNAIII inhibiting peptide against foreign-body infection by methicillin-resistant Staphylococcus aureus

Journal of Infection ◽

10.1016/j.jinf.2012.09.012 ◽

2012 ◽

Vol 65 (6) ◽

pp. 586-588 ◽

Cited By ~ 3

Author(s):

C. Garrigós ◽

O. Murillo ◽

J. Lora-Tamayo ◽

M. Vivas ◽

F. Tubau ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Foreign Body ◽

Methicillin Resistant Staphylococcus Aureus ◽

Methicillin Resistant

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Reduced susceptibility to daptomycin in methicillin-resistant Staphylococcus aureus isolated from catheter-related bloodstream infections

10.21203/rs.3.rs-970680/v1 ◽

2021 ◽

Author(s):

Sho Ohyatsu ◽

Tomoyuki Nariyama ◽

Kotaro Matsumoto ◽

Yuki Moritoki ◽

Kentaro Kikuchi

Keyword(s):

Staphylococcus Aureus ◽

Blood Culture ◽

Drug Treatment ◽

Methicillin Resistant Staphylococcus Aureus ◽

Bloodstream Infections ◽

High Dose ◽

Methicillin Resistant ◽

Treatment Methods ◽

History Of ◽

The Mean

Abstract Background The appearance of reduced susceptibility to daptomycin in methicillin-resistant Staphylococcus aureus (MRSA) has recently been reported. It is unclear how likely MRSA involved in catheter-related bloodstream infections (CRBSI) is to dampen susceptibility to daptomycin. We investigated the minimum inhibitory concentrations (MIC) of daptomycin in MRSA isolated from the blood of patients with CRBSI and examined how it was affected by previous anti-MRSA drug treatment. Methods A total of 115 patients whose blood culture samples were found to contain MRSA were enrolled in this study. The MIC of daptomycin and vancomycin and whether the subjects had a history of anti-MRSA drug treatment were investigated and compared between the CRBSI and non-CRBSI groups. Results The mean MIC of daptomycin was significantly higher for the 46 CRBSI-related MRSA isolates than for the 69 non-CRBSI-related MRSA isolates (0.78 vs. 0.33, respectively; p<0.0001). Among the CRBSI-related MRSA isolates, those collected from patients with a history of anti-MRSA drug treatment had significantly higher MIC (1.27 vs. 0.53, respectively; p <0.01). During treatment, MRSA was detected again in 10 CRBSI and 4 non-CRBSI patients, and all of the CRBSI-related MRSA isolates exhibited 1-2 log2 increases in their daptomycin MIC. Conclusions It is considered that when MRSA in catheter biofilms is exposed to anti-MRSA drugs, strains with reduced susceptibility to daptomycin are able to survive and disperse into the blood. Catheters should be removed if an MRSA-induced CRBSI is suspected. Further study of whether high-dose daptomycin treatment is effective when catheters cannot be immediately removed is needed.

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Rapid Antibacterial Activity of Cannabichromenic Acid against Methicillin-Resistant Staphylococcus aureus

Antibiotics ◽

10.3390/antibiotics9080523 ◽

2020 ◽

Vol 9 (8) ◽

pp. 523

Author(s):

Maria Galletta ◽

Tristan A. Reekie ◽

Gayathri Nagalingam ◽

Amy L. Bottomley ◽

Elizabeth J. Harry ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibacterial Activity ◽

Bactericidal Activity ◽

Methicillin Resistant Staphylococcus Aureus ◽

Lipid Membrane ◽

Bacterial Species ◽

High Dose ◽

Methicillin Resistant ◽

Microscopic Evaluation ◽

Bacterial Lipid

Methicillin-resistant Staphylococcus aureus (MRSA) has proven to be an imminent threat to public health, intensifying the need for novel therapeutics. Previous evidence suggests that cannabinoids harbour potent antibacterial activity. In this study, a group of previously inaccessible phytocannabinoids and synthetic analogues were examined for potential antibacterial activity. The minimum inhibitory concentrations and dynamics of bacterial inhibition, determined through resazurin reduction and time-kill assays, revealed the potent antibacterial activity of the phytocannabinoids against gram-positive antibiotic-resistant bacterial species, including MRSA. One phytocannabinoid, cannabichromenic acid (CBCA), demonstrated faster and more potent bactericidal activity than vancomycin, the currently recommended antibiotic for the treatment of MRSA infections. Such bactericidal activity was sustained against low-and high-dose inoculums as well as exponential- and stationary-phase MRSA cells. Further, mammalian cell viability was maintained in the presence of CBCA. Finally, microscopic evaluation suggests that CBCA may function through the degradation of the bacterial lipid membrane and alteration of the bacterial nucleoid. The results of the current study provide encouraging evidence that cannabinoids may serve as a previously unrecognised resource for the generation of novel antibiotics active against MRSA.

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Treatment of experimental foreign body infection caused by methicillin-resistant Staphylococcus aureus.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.34.12.2312 ◽

1990 ◽

Vol 34 (12) ◽

pp. 2312-2317 ◽

Cited By ~ 87

Author(s):

J C Lucet ◽

M Herrmann ◽

P Rohner ◽

R Auckenthaler ◽

F A Waldvogel ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Foreign Body ◽

Methicillin Resistant Staphylococcus Aureus ◽

Methicillin Resistant

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Importance of penicillinase production for activity of penicillin alone or in combination with sulbactam in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.5.1219 ◽

1996 ◽

Vol 40 (5) ◽

pp. 1219-1224 ◽

Cited By ~ 7

Author(s):

B Fantin ◽

J Pierre ◽

N Castéla-Papin ◽

L Saint-Julien ◽

H Drugeon ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Body Weight ◽

Synergistic Effect ◽

Methicillin Resistant Staphylococcus Aureus ◽

Methicillin Resistance ◽

Limiting Factor ◽

High Dose ◽

Methicillin Resistant

The activity of penicillin, alone and in combination with sulbactam, against a heterogeneously methicillin-resistant, penicillinase-producing clinical isolate of Staphylococcus aureus and its penicillinase-negative derivative was investigated in vitro and in a rabbit experimental endocarditis model. Penicillin was significantly more effective than vancomycin against the penicillinase-negative derivative in vivo (P < 0.001), and it sterilized 25% of the vegetations. The combination of penicillin and sulbactam exhibited an in vivo synergistic effect on the penicillinase-producing strain (P < 0.01) but did not produce any advantage over treatment with vancomycin, even when a high dose of sulbactam was used (100 mg/kg of body weight every 6 h). This combination was significantly less effective against the penicillinase-producing strain than was penicillin alone against the penicillinase-negative derivative (P < 0.03). In addition, the most resistant subpopulation of the surviving bacteria, which grew on agar containing 16 micrograms of methicillin per ml, was detected in 5 of 6 animals treated with penicillin and a high dose of sulbactam against the penicillinase-producing strain compared with only 1 of 12 animals treated with penicillin alone against the penicillinase-negative derivative (P < 0.01). We conclude that penicillin is highly effective against penicillinase-negative methicillin-resistant S. aureus and that penicillinase production, rather than methicillin resistance, appears to be the limiting factor for the activity of the penicillin-sulbactam combination against penicillinase-producing, methicillin-resistant S. aureus.

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