During the study period, a total of 11634 patient-days was followed up and an average of 50.4% of patients was exposed to some antimicrobial (Additional file 1). The intensive care unit was the ward that contained the largest proportion of patients using ATM (86%; ICU vs SUR, MED, PNE / INF, PED; p <0.05), followed by pneumology/infectology (62%; PNE / INF vs SUR, MED; p <0.05) and pediatrics (61%; PED vs SUR, MED; p <0.05) (Table 1).
Overall, the most prescribed classes were the 1st generation cephalosporins (25.0%), fluoroquinolone (13.2%), and carbapenems (8.4%) (Additional file 1). The 1st generation cephalosporins were the most prescribed classes both in surgical clinic (49.9%; SUR vs MED, PNE / INF, ICU; p <0.05) and in pediatrics (34.5%; PED vs MED, PNE / INF; p <0.05). The medical clinic had a higher number of prescriptions referring to 3rd generation cephalosporins (14.7%; MED vs SUR, ICU; p <0.05), pneumology/infectology had a higher number of antifungals (16%; PNE / INF vs SUR, PED; p <0.05) and the ICU prevailed the prescription of carbapenems (19.2%; ICU vs SUR, MED, PNE / INF, PED; p <0.05) (Table 1).
In 376 days for every 1000 days of hospitalization, patients were receiving antimicrobial therapy (LOT = 376/1000pd) (Additional file 1). Comparing hospital wards, the ICU was where patients were exposed to ATMs for the longest time (753 DOT / 1000pd; ICU vs SUR, MED, PED; p <0.05), followed by pneumology/infectology (470 DOT / 1000pd; PNE / INF vs SUR, MED; p <0.05). The calculated global DOT / LOT ratio showed that each patient received an average of 1.5 antimicrobials during the hospital stay (Additional file 1), with a higher number within the ICU (2 DOT / LOT; ICU vs SUR, MED, PNE / INF, PED; p <0.05) (Table 1).
Table 1. Distribution of use antimicrobial, by hospital ward, 2018.
VARIABLES
|
WARDS
|
SUR
|
MED
|
PNE/INF
|
PED
|
ICU
|
p-value
|
Use of antimicrobials (%)
|
38a
|
42b
|
62c(ab)
|
61d(ab)
|
86e(abcd)
|
0.000*
|
Number of prescriptions (%)
|
|
|
|
|
|
|
First-generation cephalosporins IV/PO
|
49.4a(bce)
|
3.8b
|
1.4c
|
34.5d(bc)
|
9.4e
|
0.000*
|
Fluoroquinolones IV/PO
|
20.5a
|
14.1b
|
11.2c
|
3.6d(abe)
|
13.5e
|
0.000*
|
Carbapenems IV
|
1.7a(bc)
|
11.5b
|
8.8c
|
6.3d
|
19.2e(abcd)
|
0.000*
|
Third-generation cephalosporins IV
|
6.5a
|
14.7b(ae)
|
8.5c
|
9.2d
|
4e
|
0.004*
|
Metronidazole IV/PO
|
10.1a
|
5.8b
|
1.7c(ae)
|
6.3d
|
11.1e
|
0.031*
|
Cefepime IV
|
0.8a
|
10.3b(a)
|
15.6c(ade)
|
6.0d
|
7.1e
|
0.000*
|
Clindamycin IV
|
9.1
|
7.1
|
5.1
|
2.1
|
7.4
|
0.072
|
Antifungals IV/PO
|
0.2a
|
7.1b(a)
|
16c(ad)
|
4.5d
|
6.7e
|
0.000*
|
Glycopeptides IV
|
1.1a
|
6.4b
|
3.4c
|
3d
|
10.4e(acd)
|
0.001*
|
Azithromycin IV/PO
|
0a
|
2.6b
|
9.5c(abe)
|
6.3d(ae)
|
1.7e
|
0.000*
|
Penicillins1 IV/PO
|
0.2a
|
10.3b(ae)
|
3.4c
|
8.3d(ae)
|
1e
|
0.000*
|
Co-trimoxazole IV/PO
|
0a
|
3.2b
|
10.9c(abe)
|
3.6d(a)
|
3e
|
0.000*
|
Aminoglycosides IV
|
0.4a
|
2.6b
|
4.4c
|
6.5d(a)
|
3.4e
|
0.025*
|
LOT/1000pd
|
300a
|
262b
|
470c(ab)
|
382d
|
753e(abd)
|
0.000*
|
DOT/1000pd
|
|
|
|
|
|
|
Fluoroquinolones IV/PO
|
108a
|
57b
|
71c
|
24d
|
147e(bd)
|
0.001*
|
First-generation cephalosporins IV/PO
|
123a(bc)
|
5b
|
6c
|
94d(bc)
|
73e(bc)
|
0.000*
|
Carbapenems IV
|
11a
|
43b
|
84c(a)
|
40d
|
368e(abd)
|
0.000*
|
Third-generation cephalosporins IV
|
43
|
50
|
64
|
61
|
35
|
0.775
|
Cefepime IV
|
8a(ce)
|
32b
|
95c
|
47d
|
114e
|
0.000*
|
Metronidazole IV/PO
|
56a
|
12b
|
8c(ad)
|
59d
|
119e(bc)
|
0.000*
|
Antifungals IV/PO
|
1a(ce)
|
24b
|
83c
|
40d
|
118e
|
0.000*
|
Co-trimoxazole IV/PO
|
0a(cde)
|
4b(c)
|
121c
|
25d
|
72e
|
0.000*
|
Clindamycin IV
|
47
|
28
|
37
|
12
|
75
|
0.099
|
Glycopeptides IV
|
8a
|
25b
|
36c
|
10d
|
183e(abcd)
|
0.000*
|
Aminoglycosides IV
|
6
|
16
|
32
|
34
|
83
|
0.055
|
Penicillins1 IV/PO
|
1a(bd)
|
35b
|
18c
|
38d
|
13e(bd)
|
0.000*
|
Azithromycin IV/PO
|
0a(cd)
|
8b(c)
|
40c
|
31d
|
23e
|
0.000*
|
DOT/LOT ratio
|
1.4a
|
1.3b
|
1.5c
|
1.4d
|
2.0e(abcd)
|
0.000*
|
Subtitle: SUR - Surgical Clinic, MED - Medical Clinic, PNE/INF - Pneumology / Infectology, PED - Pediatrics, ICU - Intensive Care Unit.
1 penicillin/penicillin with beta-lactamase inhibitor.
a,b,c,d,e – statistical differences per line (Bonfferroni *p <0.05)
In the hospital, the therapy time was longer for fluoroquinolone (75 DOT / 1000pd), followed by 1st generation cephalosporins (66 DOT / 1000pd), and carbapenems (61 DOT / 1000pd) (Additional file 1). Exposure time to 1st generation cephalosporins in the surgical clinic (123 DOT / 1000pd; SUR vs MED, PNE / INF; p <0.05) and in pediatrics (94 DOT / 1000pd; PED vs MED, PNE / INF; p <0.05) was superior to the other antimicrobial classes. Higher exposures were also observed for fluoroquinolone in the medical clinic (57 DOT / 1000pd), co-trimoxazole in pneumology/infectology (121 DOT / 1000pd) and carbapenems in the ICU (368 DOT / 1000pd; ICU vs SUR, MED, PED; p <0.05) (Table 1).
The incidence of antimicrobial resistance, globally, for both Methicillin R and Carbapenem R, was 1 per 1000 patient-days (Additional file 1), presenting higher rate of Carbapenem R in ICU (3; ICU vs SUR, PNE / INF, PED; p <0.05) (Table 2).
Table 2. Incidence of antimicrobial resistance per 1000 patient-days, by hospital ward, 2018.
ANTIMICROBIAL RESISTANCE
|
WARDS
|
SUR
|
MED
|
PNE/INF
|
PED
|
ICU
|
p-value
|
Methicillin R
|
0
|
1
|
2
|
0
|
3
|
0.101
|
Carbapenem R
|
0a
|
2b
|
0c
|
0d
|
3e(a,c,d)
|
0.005*
|
Subtitle: SUR - Surgical Clinic, MED - Medical Clinic, PNE/INF - Pneumology / Infectology, PED - Pediatrics, ICU - Intensive Care Unit.
Methicillin R - Methicillin-resistant Staphylococcus aureus
Carbapenem R - Carbapenem Resistance in Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii
a,b,c,d,e – statistical differences per line (Bonfferroni *p <0.05)
Overall, diagnoses for the use of antimicrobials involved surgical prophylaxis (35.6%), respiratory infections (23.6%), and sepsis (13.9%) (Additional file 1). Surgical prophylaxis was the main indication for the use of antimicrobials in the surgical clinic (80.8%; SUR vs MED, PNE / INF; p <0.05) and in pediatrics (36.2%; PED vs MED, PNE / INF; p <0.05). Respiratory infections were higher in the medical clinic (22.4%) and pneumology/infectology (39.1%; PNE / INF vs SUR; p <0.05), while in the ICU the diagnosis of sepsis prevailed (34.1%; ICU vs SUR; p <0.05). There was no significant difference in the diagnosis of skin / soft tissue infections, urinary infections, abdominal infections, and others (Table 3).
Table 3. Distribution of diagnostic for the use of antimicrobials, by hospital ward, 2018.
DIAGNOSTIC
(%)
|
WARDS
|
SUR
|
MED
|
PNE/INF
|
PED
|
ICU
|
p-value
|
Surgical prophylactic
|
80.8a(bc)
|
0b
|
0c
|
36.2d(bc)
|
33.9e
|
0.000*
|
Respiratory infection
|
4.2a
|
22.4b
|
39.1c(a)
|
32.9d
|
19.8e
|
0.017*
|
Sepsis
|
0a
|
19.0b
|
19.6c
|
5.4d
|
34.1e(a)
|
0.033*
|
Skin/soft tissue infection
|
2.5
|
17.2
|
16.3
|
10.1
|
0.9
|
0.154
|
Urinary infection
|
2.5
|
19.0
|
14.1
|
5.4
|
3.8
|
0.749
|
Abdominal infection
|
7.5
|
19.0
|
1.1
|
0.7
|
7.5
|
0.134
|
Others
|
2.5
|
3.4
|
9.8
|
9.4
|
0
|
0.141
|
Subtitle: SUR - Surgical Clinic, MED - Medical Clinic, PNE/INF - Pneumology / Infectology, PED - Pediatrics, ICU - Intensive Care Unit.
Others - Surgical Site Infection, Visceral Leishmaniasis, Febrile Neutropenia, Bacterial Endocarditis.
a,b,c,d,e – statistical differences per line (Bonfferroni *p <0.05)
Trend
The time series analysis reveals a significant reduction in the use of antimicrobials, globally (-1.0%; p <0.05), and in particular, in the surgical clinic (-1.6%; p <0.05), on the other hand, there was an increase in the medical clinic (2.6%; p <0.05) (Additional file 1; Additional file 2). Overall, there was a significant decrease in the use of aminoglycosides (-0.3%; p <0.05), and a significant increase for carbapenems (0.4%; p <0.05). The surgical clinic obtained a significant reduction in the number of aminoglycosides prescriptions (-0.1%; p <0.05). In the medical clinic, there was a reduction in the number of penicillins (-1.9%; p <0.05) and an increase in the number of carbapenems (1.0%; p <0.05). In pneumology / infectology, reductions were observed for 1st generation cephalosporins (-0.3%; p <0.05) and aminoglycosides (-1.1%; p <0.05). In pediatrics, there was an increase in the number of azithromycin prescriptions (0.9%; p <0.05). There was no significant change in the ICU prescriptions (Additional file 1; Additional file 2).
There were no significant changes in the duration of antimicrobial therapy (LOT/1000pd) and the DOT / LOT ratio, in general, and between the units analyzed (Additional file 1; Additional file 2). Regarding the time of use single of antimicrobials, in hospital, significant decreases were observed for use of 1st generation cephalosporins (-2.9 DOT/1000pd; p <0.05), and aminoglycosides (-0.4 DOT/1000pd; p <0.05). These falls were mostly observed in the surgical clinic (1st generation cephalosporins -10.6 DOT/1000pd and aminoglycosides -1.8 DOT/1000pd; p <0.05), with increased time for use of glycopeptides (1.7 DOT/1000pd; p <0.05). In the medical clinic, there was reduced the time in the use of penicillins (-4.9 DOT/1000pd; p <0.05) and extended the therapy to carbapenems (5.6 DOT/1000pd; p <0.05). In pneumology / infectology, the only significant change observed was a reduction in the time of use of aminoglycosides (-7.3 DOT/1000pd; p <0.05). In pediatrics, azithromycin use time increased (3.6 DOT/1000pd; p <0.05). In the ICU there was a decrease in the time of use of clindamycin (-23.5 DOT/1000pd; p <0.05), and an increase for carbapenems (24.4 DOT/1000pd; p <0.05).
Overall, incidence rates of antimicrobial resistance revealed an important increase of Methicillin R (0.1; p<0.05), especially in the surgical clinic (0.1; p <0.05) and in the ICU (1.0; p <0.05) (Additional file 1; Additional file 2).