Pre-optimized phage therapy on secondary Acinetobacter baumannii infection in four critical COVID-19 patients

Figures & data

Figure 1. Study diagram. Flow diagram of the conventional phage therapy procedure for Patient 1 and the pre-optimized procedure (via next evolution phage-typing, NEPT) for the rest 3 patients.

Figure 2. Changes of bacterial phage susceptibility profiles upon in-vivo and in-vitro phage challenges. Representative CRAB isolates and their phage-resistant derivates induced by phage therapy or in-vitro next evolution phage-typing (NEPT) were analysed by Phage-typing and multilocus-sequence typing (MLST) using both the Pasteur and the Oxford schemes.

Table 1. Baseline characteristics, treatments, and outcomes of the patients*.

	Patient 1		Patient 2		Patient 3	Patient 4
Characteristics at baseline
Age-year	62		64		81	78
SARS-CoV-2 status (RNA, Antibodies)^a	(Negative, Positive)		(Negative, Positive)		(Negative, Positive)	(Negative, Positive)
CRAB infections (days after admission to ICU)	Respiratory tract (18)		Respiratory tract (21)	Wound (34)^b	Respiratory tract (40)	Respiratory tract (18)
Days before phage therapy	11		38	1	6	50
CRAB detected samples	Sputum, BALF		Sputum, BALF	Secretion	Sputum, BALF	Sputum, BALF, Urine
Coexisting infections	Candida albicans		Candida albicans, Ralstonia mannitolilytica	ND	Candida albicans, Candida glabrata	Candida albicans, CSKP, Sphingomonas paucimobilis
Antibiotic and life-support treatment
Principal antibiotics (Susceptibility)	CFP/SUL (S/I)		CFP/SUL (S/I), TGC (S), LEV (S/I)		MPM (R), CFP/SUL (S/I)	TGC (S), IPM (R), CFP/SUL (S/I)
Life-support status	MV, ECMO		MV, ECMO		MV, ECMO, CRRT	MV
Phage therapy
Therapeutic phages	1ɸ	2ɸ	2ɸ	2ɸ	2ɸ	2ɸ
Administrated route	Inhalation	Inhalation	Inhalation	Wet compress	Inhalation	Inhalation
Primary indicators
Semi-quantitative CRAB (24 h before, after)^c	(4+, 2+)	(4+, 2+)	(3+, 2+)	(4+, Negative)	(4+, Negative)	(4+, 2+)
Phage resistance of evolved CRAB	Yes	Yes	Yes	NA	NA	Yes
Adverse event	fever, IL-6&IL-8 storm	ND	ND	ND	ND	ND
Outcome	Discharged from hospital Day 30		Discharged from hospital Day 9		Died Day 10	Discharged from ICU Day 7, Died Day 40

*SARS-CoV-2, Severe acute respiratory syndrome coronavirus-2; CRAB, Carbapenem-resistant Acinetobacter baumanni; ICU, Intensive care unit; BALF, Bronchoalveolar lavage fluid; ND, Not detectable; CSKP, Carbapenem-resistant Klebsiella Pneumoniae; CFP/SUL, Cefoperazone-sulbactam; TGC, Tigecycline; LEV, Levofloxacin; MPM, Meropenem; IPM, Imipenem; S, Susceptible; R, Resistant; I, Intermediate; MV, Mechanical ventilation; ECMO, Extracorporeal membrane oxygenation; CRRT, Continuous Renal Replacement Therapy; 1ɸ, ɸ124; 2ɸ, ɸ124+ɸ121; NA, Not applicable.

^a SARS-CoV-2 RNA status in throat swab and IgG/IgM status in serum.

^b Wound infection on the jugular intubation site of ECMO.

^c Semi-quantitative burden of bacteria was measured by streak-plate method.

Figure 3. Changes of clinical status within 30 days post phage therapy. Clinical status on a 7-point ordinal scale (1. dead, 2. hospitalized, on extracorporeal membrane oxygenation or invasive mechanical ventilation, 3. hospitalized, on noninvasive ventilation or high flow oxygen devices, 4. hospitalized, requiring supplemental oxygen, 5. hospitalized, not requiring supplemental oxygen, 6. not hospitalized, but unable to resume normal activities, 7. not hospitalized, with resumption of normal activities) was measured at baseline, 7, 14 and 30 days after treatment.