Objectives To describe the burden, epidemiology and outcomes of co-infections and superinfections occurring in hospitalized patients with coronavirus disease 2019 (COVID-19). Methods We performed an observational cohort study of all consecutive patients admitted for ≥48 hours to the Hospital Clinic of Barcelona for COVID-19 (28 February to 22 April 2020) who were discharged or dead. We describe demographic, epidemiologic, laboratory and microbiologic results, as well as outcome data retrieved from electronic health records. Results Of a total of 989 consecutive patients with COVID-19, 72 (7.2%) had 88 other microbiologically confirmed infections: 74 were bacterial, seven fungal and seven viral. Community-acquired co-infection at COVID-19 diagnosis was uncommon (31/989, 3.1%) and mainly caused by Streptococcus pneumoniae and Staphylococcus aureus . A total of 51 hospital-acquired bacterial superinfections, mostly caused by Pseudomonas aeruginosa and Escherichia coli , were diagnosed in 43 patients (4.7%), with a mean (SD) time from hospital admission to superinfection diagnosis of 10.6 (6.6) days. Overall mortality was 9.8% (97/989). Patients with community-acquired co-infections and hospital-acquired superinfections had worse outcomes. Conclusions Co-infection at COVID-19 diagnosis is uncommon. Few patients developed superinfections during hospitalization. These findings are different compared to those of other viral pandemics. As it relates to hospitalized patients with COVID-19, such findings could prove essential in defining the role of empiric antimicrobial therapy or stewardship strategies.
Strains were clonally related and coproduced a CTX-M-15 -lactamase. A conjugative plasmid of circa 70 kb carrying bla OXA-48 was identified. Eleven isolates showed low-level resistance to carbapenems, whereas nine showed high-level resistance. Decreased expression of OmpK36 was related to high-level resistance to carbapenems. The isolates belonged to sequence type 101 (ST101). This is the first outbreak caused by an OXA-48-producing K. pneumoniae strain in Spain.
Evidence supporting the combination of aminoglycosides with -lactams for Gram-negative bacteremia is inconclusive. We have explored the influence on survival of empirical therapy with a -lactam alone versus that with a -lactam-aminoglycoside combination by retrospectively analyzing a series of bacteremic episodes due to aerobic or facultative Gram-negative microorganisms treated with single or combination therapy. The outcome variable was a 30-day mortality. Prognostic factors were selected by regression logistic analysis. A total of 4,863 episodes were assessed, of which 678 (14%) received combination therapy and 467 (10%) were fatal. Factors independently associated with mortality included age greater than 65 (odds ratio [OR], 2; 95% confidence interval [CI], 1.6 to 2.6), hospital acquisition (OR, 1.5; 95% CI, 1.2 to 1.9), a rapidly or ultimately fatal underlying disease (OR, 2.5; 95% CI, 2 to 3.2), cirrhosis (OR, 1.9; 95% CI, 1.4 to 2.6), prior corticosteroids (OR, 1.5; 95% CI, 1.1 to 2), shock on presentation (OR, 8.8; 95% CI, 7 to 11), pneumonia (OR, 2.8; 95% CI, 1.9 to 4), and inappropriate empirical therapy (OR, 1.8; 95% CI, 1.3 to 2.5). Subgroup analysis revealed that combination therapy was an independent protective factor in episodes presenting shock (OR, 0.6; 95% CI, 0.4 to 0.9) or neutropenia (OR, 0.5; 95% CI, 0.3 to 0.9). Combination therapy improved the appropriateness of empirical therapy in episodes due to extended-spectrum -lactamase (ESBL)-or AmpC-producing Enterobacteriaceae and Pseudomonas aeruginosa. In patients with Gram-negative bacteremia, we could not find an overall association between empirical -lactam-aminoglycoside combination therapy and prognosis. However, a survival advantage cannot be discarded for episodes presenting shock or neutropenia, hence in these situations the use of combination therapy may still be justified. Combination therapy also should be considered for patients at risk of being infected with resistant organisms, if only to increase the appropriateness of empirical therapy.
A carbapenem-resistant Escherichia coli strain (DVR22) was recovered from a stool specimen from a patient with traveler's diarrhea who had traveled to India. Molecular screening led to the first identification of NDM-1 in Spain. The bla NDM-1 gene was located in a conjugative plasmid of ca. 300 kb that also contained the bla CTX-M-15 , bla TEM-1 , ⌬bla DHA-1 , and armA genes. In addition, bla NDM-1 was preceded by an ISAba125 insertion element only found in Acinetobacter spp.The emergence of carbapenem resistance among Enterobacteriaceae is a major cause of concern since carbapenems currently represent the treatment of choice for severe infections caused by multidrug-resistant strains producing extended-spectrum -lactamases (ESBLs) (8).In addition to commonly known carbapenem-hydrolyzing enzymes in Enterobacteriaceae (IMP, VIM, KPC, and OXA-48), a novel class B metallo--lactamase (NDM-1) has recently been described. This enzyme, first identified in Klebsiella pneumoniae and Escherichia coli clinical isolates recovered in Sweden from a traveler returning from India, confers resistance to all -lactams except aztreonam (22). Since then, several reports have identified bla NDM genes worldwide that have typically been associated with multidrug-resistant strains (1,5,12,(16)(17)(18)23).A 40-year-old Spanish Caucasian male reported intermittent abdominal discomfort, fever, and bloody diarrhea about 5 days before returning from India. He visited a local dispensary in India where treatment with ofloxacin and ornidazole tablets (twice a day) was prescribed for 5 days. The patient reported to the Hospital Clinic of Barcelona 1 day after his return, still complaining of bloody diarrhea, although with fewer unformed stools. He was afebrile, without any sign of dehydration, and the rest of the physical examination was normal. The diarrhea resolved spontaneously over the next 9 days.A carbapenem-resistant E. coli (DVR22) strain was recovered from the stool samples of the patient, and after isolation and identification, antimicrobial susceptibility profiling analysis performed with both BD Phoenix (Becton Dickinson, Franklin Lakes, NJ) and Etest strips (AB bioMérieux, Solna, Sweden) indicated that strain DVR22 was resistant to all the antibiotics tested except tigecycline (MIC of 0.75 g/ml), fosfomycin (MIC of 32 g/ml), and colistin (MIC of 0.5 g/ml) (Table 1), presenting MICs of 8 g/ml and 16 g/ml for imipenem and meropenem, respectively, 24 g/ml for ertapenem, and 6 g/ml for doripenem (CLSI breakpoints from broth microdilution tests were used to classify the MICs obtained by Etest [7]). Screening for carbapenemase/MBL production yielded positive results when using either the cloverleaf test (modified Hodge test) or imipenem-EDTA Etest strips. PCR screening for -lactamase genes followed by DNA sequencing using specific primers (NDM-1 F, 5Ј-CCAATATTATGCACC CGGTCG-3Ј, and NDM-1 R 5Ј-ATGCGGGCCGTATGAGT GATTG-3Ј) (2, 14, 21) identified the presence of bla NDM-1 , bla CTX-M-15 , bla TEM-1 , and a partial sequence of the bla DHA-...
A carbapenem-resistant Escherichia coli isolate (sequence type 448 [ST448]) was recovered from a urine culture of a female patient with no recent record of traveling. PCR screening identified the presence of bla NDM-5 , bla TEM-1 , bla OXA-1 , bla CMY-42 , and rmtB. bla NDM-5 was carried in a conjugative IncFII-type plasmid (90 kb) together with bla TEM-1 and rmtB. The genetic environment of bla NDM-5 showed a structure similar to those of pMC-NDM and pGUE-NDM, identified in Poland and France in E. coli of African and Indian origin, respectively. C arbapenemase-producing Enterobacteriaceae (CPE) constitute a public health problem regarding both hospital-and community-acquired infections (1). Despite increasing reports of CPE in Europe, predominantly in southern European countries, the prevalence of CPE in Spain still remains relatively low although it is steadily increasing, with only a few outbreaks or sporadic isolates harboring VIM, KPC, OXA-48, or NDM-1 being reported (2). Since the identification of NDM-1 in a Swedish traveler returning from India (3), NDM enzymes have received special attention due to their rapid global spread and frequent association with additional resistance genes (4). There are currently 12 NDM variants (http://www.lahey.org), differing by one or two amino acid substitutions, that may display slightly different hydrolytic capabilities (4).The aim of this study was to characterize an NDM-5-producing Escherichia coli recovered in Spain from a nontraveler patient.A 78-year-old Spanish Caucasian female with a history of acute pyelonephritis treated with ceftriaxone (1 g/24 h) was positive for a carbapenem-resistant E. coli strain (HC105) in urine samples 15 days after the end of treatment. The patient was asymptomatic at this stage. The susceptibility testing using Etest strips (AB-bioMérieux, Solna, Sweden) and interpreted according to the EUCAST guidelines (version 4.0, 2014; http://www.eucast.org) indicated that HC105 was resistant to all of the antibiotics tested except tigecycline, fosfomycin, and colistin (MICs of 0.38 g/ml, 0.5 g/ml, and 0.125 g/ml, respectively) and had ertapenem, imipenem, and meropenem MICs of Ͼ32 g/ml (Table 1). The patient was successfully treated with fosfomycin (2 g/8 h), and no additional CPE were recovered. The screening of HC105 for carbapenemase/metallo--lactamase (MBL) production using either the modified Hodge test or imipenem-EDTA Etest strips yielded positive results, suggesting carriage of an MBL. The PCR and sequence analysis for carbapenemase, extended-spectrum -lactamase (ESBL), and plasmid-mediated AmpC cephalosporinaseencoding genes (5, 6) identified the presence of bla NDM-5 , bla TEM-1 , bla OXA-1 , and bla . The screening for 16S rRNA methylase genes (7) also identified the rmtB gene, conferring highlevel resistance to all aminoglycosides, in agreement with the susceptibility profile (Table 1). The multilocus sequence typing (http: //mlst.ucc.ie/mlst/dbs/Ecoli) and PCR-based phylogroup analysis (8) assigned E. coli HC105 to sequence type 4...
The high percentage of resistance to quinolones in ETEC and EAEC isolated from travellers to North Africa and India is a matter for concern. These agents should therefore be used with caution in patients with traveller's diarrhoea returning from these geographical areas.
The aim of this study was to describe the prevalence and characteristics of knee prosthetic joint infections due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. From 2000 to 2007, 132 infections out of 5,076 arthroplasties (2.6%) were registered. Seven out of 132 infections (5.3%) were due to ESBL-producing Enterobacteriaceae, Escherichia coli in six cases and Klebsiella pneumoniae in one. Open debridement and retention of the implant was the first surgical approach and all patients received intravenous carbapenems. Relapse was documented in four cases and remission in three. Therefore, debridement without prosthesis removal was associated with a high failure rate.
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