Bacterial co-infections, secondary infections and antimicrobial use among hospitalized COVID-19 patients in the sixth wave in Pakistan: findings and implications

Figures & data

Table 1. Demographic and clinical characteristics of the study population (N = 284).

Variables	N (%)				P-value
	Total	H1	H2	H3
	(N = 284)	(N = 74)	(N = 119)	(N = 91)
Age
10–30 years	26 (9.2)	6 (8.1)	13 (10.9)	7 (7.7)	0.213
30–50 years	144 (50.7)	34 (45.9)	68 (57.1)	42 (46.2)
>50 years	114 (40.1)	34 (45.9)	38 (31.9)	42 (46.2)
Sex
Male	190 (66.9)	50 (67.6)	80 (67.2)	60 (65.9)	0.971
Female	94 (33.1)	24 (32.4)	39 (32.8)	31 (34.1)
Residence
Rural	81 (28.5)	25 (33.8)	30 (25.2)	26 (28.6)	0.439
Urban	203 (71.5)	49 (66.2)	89 (74.8)	65 (71.4)
Comorbidity*
Yes	115 (40.5)	32 (43.2)	48 (40.3)	35 (38.5)	0.823
No	169 (59.5)	42 (56.8)	71 (59.7)	56 (61.5)
Hospital Ward
Medical	199 (70.1)	48 (64.9)	91 (76.5)	60 (65.9)	0.134
ICU	85 (29.9)	26 (35.1)	28 (23.5)	31 (34.1)
Severity of COVID-19
Asymptomatic	9 (3.2)	5 (6.8)	3 (2.5)	1 (1.1)	0.030
Mild	99 (34.9)	25 (33.8)	50 (42.0)	24 (26.4)
Moderate	86 (30.3)	16 (21.6)	38 (31.9)	32 (35.2)
Severe	67 (23.6)	20 (27.0)	19 (16.0)	28 (30.8)
Critical	23 (8.1)	8 (10.8)	9 (7.6)	6 (6.6)
Oxygen therapy
Yes	90 (31.7)	28 (37.8)	28 (23.5)	34 (37.4)	0.043
No	194 (68.3)	46 (62.2)	91 (76.5)	57 (62.6)
Invasive mechanical ventilation
Yes	26 (9.2)	9 (12.2)	8 (6.7)	9 (9.9)	0.425
No	194 (68.3)	65 (87.8)	111 (93.3)	82 (90.1)
Laboratory findings
X-Ray abnormalities	123 (43.3)	34 (45.9)	38 (31.9)	51 (56.0)	0.002
Elevated WBCs	105 (37.0)	29 (39.2)	37 (31.1)	39 (42.9)	0.195
Elevated CRP	100 (35.2)	22 (29.7)	37 (31.1)	41 (45.1)	0.057
Length of hospital stay
<7 days	41 (14.4)	8 (10.8)	13 (10.9)	20 (22.0)	0.001
7–14 days	134 (47.2)	37 (50.0)	70 (58.8)	27 (29.7)
≥15 days	109 (38.4)	29 (39.2)	36 (30.3)	44 (48.4)

NB: *Diabetes = 62 patients, Hypertension = 53 patients, cardiovascular disease = 23 patients, respiratory disease = 12 patients; CRP=C reactive protein; H=hospital; ICU=intensive care unit; WBC=white blood cell.

Table 2. Detail of prescribed antibiotics amid the sixth wave of COVID-19 in Pakistan.

Variables	N (%)
	Total	H1	H2	H3
Number of patients prescribed antibiotics (N = 284)	261 (91.9)	67	109	85
Total number of prescribed antibiotics	457	126	193	138
Average number of prescribed antibiotics per patient ± SD (N = 284)	1.61 ± 0.86	1.70 ± 0.98	1.62 ± 0.88	1.52 ± 0.72
Number of antibiotics per patient (N = 261)
One antibiotic	107 (41.0)	23	44	40
Two antibiotics	124 (47.5)	33	49	42
Three or more antibiotics	30 (11.5)	11	16	3
Duration of antibiotic therapy (N = 457)
1–5 days	67 (14.7)	16	27	24
6–10 days	218 (47.7)	72	92	54
>11 days	172 (37.6)	38	74	60
Route of administration (N = 457)
Oral	111 (24.3)	37	49	25
Intravenous	346 (75.7)	89	144	113

NB: H=hospital, SD=standard deviation.

Table 3. Prescribed antibiotics according to their ATC classification accross the three hospitals.

ATC class	Name of antibiotics (ATC code)	N (%)
		H1	H2	H3	Total
Third-generation cephalosporins	Ceftriaxone (J01DD04)	31 (24.6)	53 (27.5)	30 (21.7)	114 (24.9)
	Cephoperazone + beta-lactamase inhibitor (J01DD12)	9 (7.1)	12 (6.2)	8 (5.8)	29 (6.3)
Macrolides	Azithromycin (J01FA10)	26 (20.7)	42 (21.8)	24 (17.4)	92 (20.1)
Piperacillin and an enzyme inhibitor	Piperacillin + enzyme inhibitor (tazobactam) (J01CR05)	23 (18.2)	23 (11.9)	16 (11.6)	62 (13.6)
Carbapenems	Meropenem (J01DH02)	14 (11.1)	27 (14.0)	18 (13.0)	59 (12.9)
Fluoroquinolones	Ciprofloxacin (J01MA02)	4 (3.1)	7 (3.6)	10 (7.3)	21 (4.6)
	Levofloxacin (J01MA12)	1 (0.8)	4 (2.0)	5 (3.6)	10 (2.2)
	Moxifloxacin (J01MA14)	1 (0.8)	4 (2.0)	0	5 (1.1)
Other antibacterials	Linezolid (J01XX08)	6 (4.8)	5 (2.6)	11 (8.0)	22 (4.8)
Glycopeptides	Vancomycin (J01XA01)	6 (4.8)	5 (2.6)	8 (5.8)	19 (4.2)
Amoxicillin and beta-lactamase inhibitor	Amoxicillin+ Beta-lactamase inhibitors (J01CR02)	2 (1.6)	5 (2.6)	3 (2.2)	10 (2.2)
Penicillins with extended spectrum	Amoxicillin (J01CA04)	2 (1.6)	3 (1.6)	5 (3.6)	10 (2.2)
Fourth-generation cephalosporins	Cefepime (J01DE01)	1 (0.8)	3 (1.6)	0	4 (0.9)

NB: ATC=Anatomical Therapeutic Chemical Classification; H=hospital.

Figure 1. Prescribed antibiotics according to WHO AWaRe classification among the participating hospitals.NB: ‘Access’, ‘Watch’ and ‘Reserve’ antibiotics based on the AWaRe list [63,64].

Table 4. Comparison of antibiotic usage among selected variables.

Variables	No. of antibiotics (Mean ± SD)	P-value
Hospital (H)
H1	1.70 ± 0.98	0.374
H2	1.62 ± 0.88
H3	1.52 ± 0.72
Age
10–30 years	1.31 ± 0.74	0.011
30–50 years	1.53 ± 0.84
>50 years	1.78 ± 0.89
Sex
Male	1.66 ± 0.87	0.133
Female	1.50 ± 0.84
Residence
Rural	1.56 ± 0.82	0.508
Urban	1.63 ± 0.88
Comorbidity*
Yes	1.77 ± 0.83	0.008
No	1.50 ± 0.87
Ward
Medical	1.49 ± 0.80	<0.001
ICU	1.88 ± 0.93
Severity of COVID-19
Asymptomatic	0.56 ± 0.88	<0.001
Mild	1.26 ± 0.78
Moderate	1.60 ± 0.60
Severe	2.00 ± 0.85
Critical	2.39 ± 0.94
Oxygen therapy
Yes	2.10 ± 0.89	<0.001
No	1.38 ± 0.75
Invasive mechanical ventilation
Yes	2.35 ± 0.98	<0.001
No	1.53 ± 0.81
X-Ray abnormalities
Yes	1.93 ± 0.85	<0.001
No	1.36 ± 0.79
Elevated White blood cell count
Yes	1.96 ± 0.89	<0.001
No	1.40 ± 0.78
Elevated C-reactive protein
Yes	1.99 ± 0.82	<0.001
No	1.40 ± 0.81
Length of stay
<7 days	1.10 ± 0.83	<0.001
7–14 days	1.45 ± 0.71
≥15 days	2.00 ± 0.88

NB: * See Table 1 for details of co-morbidities.

Table 5. Pairwise comparisons of antibiotic use among age groups, COVID-19 severity, and length of hospital stay.

Comparison	Mean difference	SE	95% CI
			Lower bound	Upper bound	P-value*
Age (years)
10–30 vs 31–50	−0.22	0.18	−0.65	0.21	0.445
10–30 vs > 50	−0.47	0.19	−0.91	−0.04	0.029
31–50 vs > 50	−0.25	0.11	0.00	0.50	0.048
COVID-19 severity
Asymptomatic vs mild	−0.71	0.27	−1.44	0.02	0.064
Asymptomatic vs moderate	−1.05	0.27	−1.79	−0.31	0.001
Asymptomatic vs severe	−1.44	0.27	−2.19	−0.70	<0.001
Asymptomatic vs critical	−1.84	0.30	−2.66	−1.01	<0.001
Mild vs moderate	−0.34	0.11	−0.65	−0.03	0.022
Mild vs severe	−0.74	0.12	−1.07	−0.40	<0.001
Mild vs critical	−1.13	0.17	−1.62	−0.64	<0.001
Moderate vs severe	−0.40	0.13	−0.74	−0.05	0.015
Moderate vs critical	−0.79	0.18	−1.28	−0.29	<0.001
Severe vs critical	−0.39	0.19	−0.90	0.12	0.216
Length of hospital stay (days)
<7 vs 7–14	−0.35	0.14	−0.69	−0.01	0.038
<7 vs > 15	−0.90	0.15	−1.25	−0.56	<0.001
7–14 vs > 15	−0.55	0.10	−0.79	−0.31	<0.001

NB: ^aTukey HSD test.

Table 6. Factors associated with increased use of antibiotics among COVID-19 patients.

Coefficients^a
Model	Unstandardized Coefficients		Standardized Coefficients	t	P	95% CI for B
	B	SE	β			Lower bound	Upper bound
(Constant)	0.576	0.916		0.629	0.530	−1.228	2.379
Age	0.050	0.081	0.037	0.618	0.537	−0.110	0.210
Comorbidity	−0.006	0.105	−0.003	−0.054	0.957	−0.213	0.202
Ward type	−0.101	0.132	−0.054	−0.766	0.444	−0.361	0.159
COVID Severity	0.372	0.116	0.441	3.201	0.002	0.143	0.601
Oxygen therapy	0.000	0.227	0.000	−0.001	0.999	−0.448	0.447
IMV	−0.119	0.200	−0.040	−0.594	0.553	−0.513	0.275
Abnormal X-ray	0.082	0.153	0.047	0.535	0.593	−0.220	0.384
Elevated WBC	0.050	0.156	0.028	0.324	0.747	−0.257	0.358
Elevated CRP	−0.107	0.141	−0.059	−0.757	0.450	−0.384	0.171
Length of stay	0.059	0.114	0.047	0.514	0.608	−0.166	0.284

NB: ^aDependent Variable: Total number of prescribed antibiotics; B=the unstandardized beta; SE=standard error for the unstandardized beta; β=the standardized beta coefficient; t=the t test statistic; P=probability value; CI=confidence interval; CRP=C reactive protein; IMV=invasive mechanical ventilation; SE=standard error; WBC=white blood cell.

Table 7. Findings of culture testing.

Pathogens		Number of samples (n = 11)
		Identified as co-infection	Identified as secondary infection	Total
Pseudomonas aeruginosa		-	3	3
Streptococcus pneumoniae		1	2	3
Klebsiella species		-	3	3
Staphylococcus aureus		2	-	2

Data availability statement

Additional data is available from the corresponding authors on reasonable request.