Superinfections in patients treated with Teicoplanin as anti-SARS-CoV-2 agent.

Dear Editor,

We read with interest the paper by Giacobbe et al estimating a cumulative risk of developing at least one bloodstream infection (BSI) episode (largely due to Gram‐positive pathogens) of almost 50% after 30 days at risk in severe COVID‐19 patients. Similarly, Somers et al reported an increased risk to develop bacterial superinfections, principally represented by Staphylococcus aureus ventilatory associated pneumonia (VAP), in critically ill patients infected with SARS‐CoV‐2 and treated with tocilizumab. We previously described a cohort of intubated patients affected by SARS‐CoV‐2 pneumonia treated with the best available therapy (BAT), including tocilizumab, and associated with teicoplanin. This glycopeptide antibiotic was used with a double purpose: as antiviral agent for COVID‐19 and as empiric treatment of possible S aureus superinfection since the latter may represent a major complication of respiratory viral infections. , The study showed that only 19% (4/21 subjects) of patients treated with BAT plus tocilizumab and teicoplanin had an isolation of methicillin‐resistant/teicoplanin‐susceptible S aureus from respiratory secretions, and none had Gram‐positive superinfections. Here, we reported an update of the previous data, analysing bacterial infections in a retrospective multicentric cohort study enrolling 55 mechanically ventilated, SARS‐CoV‐2‐infected patients treated with BAT and tocilizumab (Tei‐COVID Study). Reporting of the study conforms to broad EQUATOR guidelines. For 34 subjects, treatment included also a median of 8‐day (range 6‐12) course of teicoplanin administration (6 mg/kg every 24 hours with loading dose every 12 hours for three doses, started on ICU admission). Ad interim BAT was compliant with suggestion of the Italian Society of Infectious and Tropical Diseases (SIMIT) and largely based on hydroxychloroquine 200 mg twice/daily plus Azithromycin 500 mg daily. Tocilizumab 8 mg/kg (up to a maximum of 800 mg/dose) twice with an interval of 12 hours was administered in all patients. As showed in Table 1, Gram‐positive superinfections were less frequent in teicoplanin‐treated group than in untreated and their incidence in teicoplanin‐treated was lower than that observed in other studies. , In particular, among 34 patients treated, 35% (12/34) developed a superinfection and only 16% BSIs and 6% bacterial lung superinfections due to Gram‐positive pathogens. The 21 teicoplanin‐untreated patients had an incidence of Gram‐positive superinfections, comparable to what Somers and Giacobbe previously reported. Interestingly, we observed a higher number of Gram‐negative BSI and VAP probably related to the changes in the abundance of aerobic bacteria in the intestinal microbiota associated with administration of teicoplanin and SARS‐CoV‐2 infection. , Nevertheless, the higher number of Gram‐negative superinfections observed in teicoplanin‐treated group could be also influenced by a longer follow up time (median 20 days, range 4‐39) than that of the other studies.

Table 1

Characteristics of patients, including causative agents of superinfection in patients treated or untreated with Teicoplanin: comparison between the results of our data (so called ‘Tei‐COVID Study’ and highlighted in grey) and other 2 key studies

Study	Tei‐COVID Study	Somers et al 1 ,*	Giocobbe et al 2
Setting	Mechanically ventilated COVID‐19 patients	Mechanically ventilated COVID‐19 patients	ICU critically ill COVID‐19 patients
Characteristics of patient enrolled	Number: 55	154	78
	Age: 66 y ± 12.1	58 y ± 14.9	66 y (57‐70)§
	Sex: 43 M, 12 F	102 M, 54 F	70 M, 12 F
	CCI: 3 (range 0‐6)	Not reported	Not reported
Pts with a superinfection			Only BSI
Overall %	24/55 (43.6%)	62/154 (40.2%)	31/78 (39.7%)
Tocilizumab
Treated	43.6%	54%	—
Untreated	—	26%	—
Teicoplanin
Treated	12/34 (35%)	—	—
Untreated	9/21 (42, 8%)	—	—

Polymicrobial infections were considered as separate events, one for each causative organism isolated. (§) expressed as median and IQR. (*) Somers et al reported that in their study pathogen numbers can add up to > 100% due to polymicrobial infections.

Abbreviations: BSI, bloodstream infection; CCI, Charlson comorbidity index; CONS, Coagulase‐negative Staphylococcus; F, females; ICU, intensive care unit; M, males; MRSA, Methicillin‐resistant S aureus; MSSA, Methicillin‐susceptible S aureus; Pt, patients; VAP, ventilatory associated pneumonia; y, years.

Superinfection N° isolates/pts

Causative microbiology↓

BSI

12/34

VAP

31/34

BSI

12/21

VAP

18/21

BSI

12/78

VAP

41/78

BSI

8/76

VAP

22/76

BSI

23/18

BSI

22/60

Based on our data, the use of teicoplanin could have represented a contributing factor in the reduction of the incidence of Gram‐positive superinfections in mechanically ventilated patients with COVID‐19. Further investigations are needed to clarify the possible impact of teicoplanin on host microbiome and on the possible development of glycopeptide resistance in this setting. On the other hand, teicoplanin role as an antiviral agent for COVID‐19 still remains under investigation.

CONFLICT OF INTEREST

None to declare.