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

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

Polish Journal of Microbiology

Volume 68 (2019): Issue 1 (March 2019)

By: NELLY M. MOHAMED , AZZA S. ZAKARIA , EVA A. EDWARD and AMANY ABDEL-BARY

Open Access

|Mar 2019

Figures & Tables

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-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).

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).

(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 observation^a	(Score 0–3)
Histological observation^a	ZAB^b	MOX	LEV	CIP
Congestion	0 (40%)
	+1 (20%)	+1 (60%)	+2 (80%)	+3 (60%)
	+2 (40%)	+2 (40%)	+1 (20%)	+1 (40%)
Inflammation	0 (40%)
	+1 (20%)	+1 (60%)	+2 (80%)	+3 (60%)
	+2 (40%)	+2 (40%)	+1 (20%)	+1 (40%)
Edema	0 (40%)
	+1 (20%)	+1 (60%)	+2 (80%)	+3 (60%)
	+2 (40%)	+2 (40%)	+1 (20%)	+1 (40%)
Necrosis	0 (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 agent	MIC (μg/ml)
Antimicrobial agent	0.03	0.06	0.125	0.25	0.5	1	2	4	8	16	32	64	> 64
Zabofloxacin	10	17	25	12	7	1	32	12	0	0	0	0	0
Moxifloxacin	0	2	7	35	15	10	11	21	13	2	0	0	0
Levofloxacin	0	0	10	33	11	0	1	8	22	29	0	2	0
Ciprofloxacin	0	0	4	18	19	8	2	4	11	19	14	14	3^a

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
Strain No.	ZAB^a	MOX	LEV	CIP	gyrA	parC	parE
S37	4	8	32	64	S84L^b	S80F^c	P451S^d
S30	2	8	16	64	S84L	S80F	P451S
S5	2	4	16	64	S84L	S80F	P451S
S3	2	8	32	64	S84L	S80F	P451S
S11	0.125	0.25	8	32	S84L	None	P451S
S38	0.25	0.25	8	16	None	S80F	None
S22	0.03	0.25	4	8	None	S80F	None

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

Microorganism inoculum (CFU/mouse)	Antimicrobial agent^a	MIC (μg/ml)	Count in dissected lungs log₁₀ (CFU/ml)^b	ED50^c (mg/kg)
Methicillin-resistant S. aureus clinical isolate S19	Zabofloxacin	0.06	3.66	29.05
	Moxifloxacin	0.06	4.31	38.69
	Levofloxacin	8	4.01	> 40.00
	Ciprofloxacin	16	4.24	> 40.00

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

Antimicrobial agent	MIC (μg/ml)			% Susceptible	% Intermediate	% Resistant
Antimicrobial agent	MIC range	MIC₅₀^*	MIC₉₀^*	% Susceptible	% Intermediate	% Resistant
Zabofloxacin	0.03 – 4	0.25	2	61.2	0.9	37.9
Moxifloxacin	0.06 – 16	0.5	8	50.9	8.6	40.5
Levofloxacin	0.125 – 64	4	16	46.5	0.9	52.6
Ciprofloxacin	0.125 – > 64	8	64	42.3	1.7	56

DOI: https://doi.org/10.21307/pjm-2019-007 | Journal eISSN: 2544-4646 | Journal ISSN: 1733-1331

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Language: English

Page range: 59 - 69

Published on: Mar 27, 2019

Published by: Polish Society of Microbiologists

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

Keywords:

fluoroquinolones,

quinolone resistance-determining regions,

Related subjects:

Microbiology and virology

© 2019 NELLY M. MOHAMED, AZZA S. ZAKARIA, EVA A. EDWARD, AMANY ABDEL-BARY, published by Polish Society of Microbiologists
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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