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In Vitro and In Vivo Activity of Zabofloxacin and Other Fluoroquinolones Against MRSA Isolates from A University Hospital in Egypt

NELLY M. MOHAMED
NELLY M. MOHAMED
, 
AZZA S. ZAKARIA
AZZA S. ZAKARIA
, 
EVA A. EDWARD
EVA A. EDWARD
 e 
AMANY ABDEL-BARY
AMANY ABDEL-BARY
   | 27 mar 2019
Polish Journal of Microbiology's Cover Image
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Article Category: original-paper
Pubblicato online: 27 mar 2019
Pagine: 59 - 69
DOI: https://doi.org/10.21307/pjm-2019-007
Parole chiave
© 2019 Maryam Labibzadeh et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fig. 1.

Bactericidal activities of (A) zabofloxacin, (B) moxifloxacin, (C) levofloxacin and (D) ciprofloxacin against fluoroquinolone-resistant MRSA clinical isolate S13. Blue line, 0.5 MIC; red line, 1 MIC; green line, 2 MIC; purple line, 4 MIC. Data points are geometric means with error bars being one standard deviation of replicate experiments (n = 3).
Bactericidal activities of (A) zabofloxacin, (B) moxifloxacin, (C) levofloxacin and (D) ciprofloxacin against fluoroquinolone-resistant MRSA clinical isolate S13. Blue line, 0.5 MIC; red line, 1 MIC; green line, 2 MIC; purple line, 4 MIC. Data points are geometric means with error bars being one standard deviation of replicate experiments (n = 3).

Fig. 2.

Bactericidal activities of (A) zabofloxacin, (B) moxifloxacin, (C) levofloxacin and (D) ciprofloxacin against fluoroquinolone-sensitive MRSA clinical isolate S15. Blue line, 0.5 MIC; red line, 1 MIC; green line, 2 MIC; purple line, 4 MIC. Data points are geometric means with error bars being one standard deviation of replicate experiments (n = 3).
Bactericidal activities of (A) zabofloxacin, (B) moxifloxacin, (C) levofloxacin and (D) ciprofloxacin against fluoroquinolone-sensitive MRSA clinical isolate S15. Blue line, 0.5 MIC; red line, 1 MIC; green line, 2 MIC; purple line, 4 MIC. Data points are geometric means with error bars being one standard deviation of replicate experiments (n = 3).

Fig. 3.

Lung tissue sections dissected from mice infected with MRSA clinical isolate and treated with (A) zabofloxacin showing very mild congestion (arrow) and inflammation with scarce inflammatory cells in the interstitial spaces; (B) moxifloxacin showing moderate congestion with ectatic vessels (arrow) and moderate interstitial inflammation; (C) levofloxacin showing moderate inflammation, congestion and oedema, with a dilated lymphatic vessel (arrow); and (D) ciprofloxacin showing bronchopneumonic changes with marked congestion, oedema, inflammatory infiltration and necrosis, with accumulation of necro-inflammatory exudate within the lumen of bronchioles (arrow) (H&E x400).
Lung tissue sections dissected from mice infected with MRSA clinical isolate and treated with (A) zabofloxacin showing very mild congestion (arrow) and inflammation with scarce inflammatory cells in the interstitial spaces; (B) moxifloxacin showing moderate congestion with ectatic vessels (arrow) and moderate interstitial inflammation; (C) levofloxacin showing moderate inflammation, congestion and oedema, with a dilated lymphatic vessel (arrow); and (D) ciprofloxacin showing bronchopneumonic changes with marked congestion, oedema, inflammatory infiltration and necrosis, with accumulation of necro-inflammatory exudate within the lumen of bronchioles (arrow) (H&E x400).

Fig. 4.

(A, × 100) cross section of lung tissue dissected from mice treated with zabofloxacin showing patent alveoli, (B, × 400) clear alveolar spaces and normal vessels, the bronchioles are lined by a layer of pneumocytes (arrow).
(A, × 100) cross section of lung tissue dissected from mice treated with zabofloxacin showing patent alveoli, (B, × 400) clear alveolar spaces and normal vessels, the bronchioles are lined by a layer of pneumocytes (arrow).

Scoring of detected congestion, inflammation, oedema and necrosis in lung tissues of mice groups infected with MRSA clinical isolate S19 and treated with zabofloxacin, moxifloxacin, levofloxacin and ciprofloxacin at a dose of 20 mg/kg of body weight/day.

Histological observationa(Score 0–3)
ZABbMOXLEVCIP
Congestion0 (40%)
+1 (20%)+1 (60%)+2 (80%)+3 (60%)
+2 (40%)+2 (40%)+1 (20%)+1 (40%)
Inflammation0 (40%)
+1 (20%)+1 (60%)+2 (80%)+3 (60%)
+2 (40%)+2 (40%)+1 (20%)+1 (40%)
Edema0 (40%)
+1 (20%)+1 (60%)+2 (80%)+3 (60%)
+2 (40%)+2 (40%)+1 (20%)+1 (40%)
Necrosis0 (40%)
+1 (20%)+1 (60%)+2 (80%)+3 (60%)
+2 (40%)+2 (40%)+1 (20%)+1 (40%)

MIC distribution of zabofloxacin, moxifloxacin, levofloxacin and ciprofloxacin determined by broth microdilution method for 116 MRSA isolates.

Antimicrobial agentMIC (μg/ml)
0.030.060.1250.250.51248163264> 64
Zabofloxacin1017251271321200000
Moxifloxacin0273515101121132000
Levofloxacin001033110182229020
Ciprofloxacin0041819824111914143a

MICs of zabofloxacin, moxifloxacin, levofloxacin and ciprofloxacin for selected 7 clinical MRSA isolates with detected mutations in QRDRs.

Strain No.MIC (μg/ml)Detected Mutation in QRDRs
ZABaMOXLEVCIPgyrAparCparE
S37483264S84LbS80FcP451Sd
S30281664S84LS80FP451S
S5241664S84LS80FP451S
S3283264S84LS80FP451S
S110.1250.25832S84LNoneP451S
S380.250.25816NoneS80FNone
S220.030.2548NoneS80FNone

In vivo activities of zabofloxacin, moxifloxacin, levofloxacin and ciprofloxacin against mice infected with MRSA S19 clinical isolate.

Microorganism inoculum (CFU/mouse)Antimicrobial agentaMIC (μg/ml)Count in dissected lungs log10 (CFU/ml)bED50c (mg/kg)
Methicillin-resistant S. aureus clinical isolate S19Zabofloxacin0.063.6629.05
Moxifloxacin0.064.3138.69
Levofloxacin84.01> 40.00
Ciprofloxacin164.24> 40.00

In vitro activity of zabofloxacin, moxifloxacin, levofloxacin and ciprofloxacin against 116 MRSA clinical isolates.

Antimicrobial agentMIC (μg/ml)% Susceptible% Intermediate% Resistant
MIC rangeMIC50*MIC90*
Zabofloxacin0.03 – 40.25261.20.937.9
Moxifloxacin0.06 – 160.5850.98.640.5
Levofloxacin0.125 – 6441646.50.952.6
Ciprofloxacin0.125 – > 6486442.31.756
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