Impact of the COVID-19 pandemic on multidrug-resistant hospital-acquired bacterial infections.

Sir, We read with attention the paper by de Carvalho et al. that was recently published in this Journal [1]. The authors evaluated the incidence of carbapenem-resistant Gram-negative bacteria in device-associated infections between 2019 and 2020 and correlated their findings with the incidence and the spread of the COVID-19 pandemic. They found a significant increase in Acinetobacter baumannii infections in 2020 compared to 2019, and a consequent increase in the empiric prescription of polymyxins. To date, the impact of the COVID-19 pandemic on the occurrence of multidrug-resistant (MDR) bacteria has been evaluated in several reports [[2], [3], [4], [5]]; notably, the longer duration of antimicrobial therapy for the management of respiratory complications of COVID-19 infection may have a devastating impact on infection control, leading to possible outbreaks of MDR bacteria in hospitals. Further, data on the increased incidence of specific MDR Enterobacterales (e.g. Klebsiella pneumoniae) or meticillin-resistant Staphylococcus aureus (MRSA) are still conflicting [[6], [7], [8]]. In this study, we compared the incidence of different hospital-acquired infections (HAIs) due to MDR bacteria in the period 2017–2019 (pre-COVID-19 period) and 2020 (COVID-19 period) in hospitalized patients at Garbagnate Milanese Hospital, Milan, Italy, a tertiary referral hospital that was fully converted to a COVID-19 hospital from March 2020.

Micro-organisms were included in the analysis only if they were found in blood, sputum, or urine of patients with systemic or local symptoms of infection at least seven days after hospital admission. Systemic or local features of infection at the time of diagnosis of HAI were fever or septic shock, pneumonia demonstrated by X-ray or computed tomography of the thorax, or pyuria; any of these had to be accompanied by a raised serum C-reactive protein level. The following bacteria were considered causes of HAI: carbapenem-resistant A. baumannii (CRAB), meticillin-susceptible S. aureus (MSSA), MRSA, extended-spectrum β-lactamase (ESBL)-producing or carbapenem-resistant (CR) Escherichia coli, K. pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa, and vancomycin-susceptible or -resistant (VRE) Enterococcus faecium. Finally, we compared the incidence rate ratio (IRR) of all these HAIs in 2020 with the incidence in the period 2017–2019.

Table I summarizes the differences in the IRR of the HAI in the two periods considered. CRAB was isolated from 16 subjects in 2020 compared to 45 in 2017–2019 (P < 0.001); MRSA was diagnosed in 79 versus 311 subjects, respectively (P = 0.85). CR-E. coli was found in nine subjects in 2020 vs 0 in 2017–2019 (P < 0.001); CR-K. pneumoniae was found in 57 patients in 2020 vs 101 in 2017–2019 (P < 0.001) and CR-P. aeruginosa in 43 vs 97 patients in 2020 and 2017–2019, respectively (P = 0.001). Finally VRE was found in 27 subjects in 2020 vs 32 in 2017–2019 (P < 0.001). The IRR of ESBL-producing bacteria was not statistically significant for E. coli and P. aeruginosa; a significant, though modest, increase in ESBL-producing K. pneumoniae was observed in 2020 compared with 2017–2019 (P = 0.037), whereas a significant reduction was found for P. mirabilis (P < 0.001). The incidence of non-MDR bacteria in 2020 vs 2017–2019 was not statistically different for the majority of bacteria, except for reductions in E. coli (P < 0.001) and K. pneumoniae (P = 0.05) (Table I). These data demonstrate that the COVID-19 pandemic led to a significant increase in MDR hospital-acquired bacterial infections, specifically CRAB, carbapenem-resistant Entero-bacterales, and VRE.

Table I

Incidence of hospital-acquired infection in 2020 (COVID-19 period) vs 2017–2019 (no COVID-19 period)

	OR (CI)	RR (CI)	IRR (CI)	P
CRAB	6.75 (1.96–23.28)	1.9 (1.91–2.18)	6.91 (1.98–37.04)	<0.001
Staphylococcus aureus
MSSA	0.40 (0.12–1.31)	0.45 (0.12–1.28)	0.4 (0.08–1.29)	0.12
MRSA	1.03 (0.79–1.33)	1.02 (0.82–1.26)	1.02 (0.79–1.31)	0.85
Escherichia coli
Not resistant	0.17 (0.07–0.40)	0.21 (0.09–0.40)	0.18 (0.07–0.40)	<0.001
ESBL+	0.83 (0.64–1.07)	0.89 (0.76–1.05)	0.84 (0.68–1.06)	0.16
CR	12.23 (3.30–45.32)	3.81 (2.16–4.75)	36.15 (5.00–1584.33)	<0.001
Klebsiella pneumoniae
Not resistant	0.26 (0.06–1.08)	0.3 (0.05–1.08)	0.26 (0.03–1.00)	0.05
ESBL+	1.33 (1.01–1.73)	1.25 (1.01–1.53)	1.29 (1.02–1.66)	0.037
CR	2.39 (1.70–3.34)	1.88 (1.49–2.34)	2.24 (1.59–3.13)	<0.001
Pseudomonas aeruginosa
Not resistant	0.44 (0.16–1.25)	0.50 (0.16–1.23)	0.45 (0.12–1.25)	0.11
ESBL+	0.48 (0.67–1.05)	0.52 (0.68–1.12)	0.49 (0.66–1.05)	0.09
CR	1.84 (1.27–2.66)	1.58 (1.19–2.04)	1.78 (1.21–2.57)	0.001
Proteus mirabilis
Not resistant	1.82 (0.83–4.02)	1.57 (0.8–2.59)	1.81 (0.72–4.15)	0.13
ESBL+	0.182 (0.07–0.45)	0.22 (0.08–0.52)	0.19 (0.06–0.45)	<0.001
Enterococcus faecium
VSE	0.78 (0.37–1.68)	0.82 (0.39–1.52)	0.78 (0.32–1.69)	0.53
VRE	3.5 (2.08–5.88)	2.36 (1.68–3.07)	3.39 (1.95–5.84)	<0.001

CI, confidence interval; OR, odds ratio; IRR, incidence rate ratio; CRAB, carbapenem-resistant Acinetobacter baumannii; MSSA, meticillin-susceptible Staphylococcus aureus; MRSA, meticillin-resistant S. aureus; ESBL+, extended spectrum β-lactamase-producing; CR, carbapenem-resistant; VSE, vancomycin-susceptible Enterococcus faecium; VRE, vancomycin-resistant E. faecium.

Our data were from a single hospital based in Lombardy, an area where the prevalence of MDR bacteria was very high even before the COVID-19 pandemic. Either of these factors may partially explain the differences between our results and those from other geographical areas, where the incidence of MDR HAI declined during the COVID-19 period [4,6,8]. Nevertheless, our data show the potential for MDR bacteria to cause infections in COVID-19 patients. The infective complications due to prolonged hospitalization and immune suppression in these patients may cause a further worsening of their prognosis.

Conflict of interest statement

None declared.

Funding sources

None.