Bacterial coinfections increase the severity of respiratory viral infections and were frequent causes of mortality in influenza pandemics but have not been well characterized in patients with ...coronavirus disease 2019 (COVID-19). The aim of this review was to identify the frequency and microbial etiologies of bacterial coinfections that are present upon admission to the hospital and that occur during hospitalization for COVID-19. We found that bacterial coinfections were present in <4% of patients upon admission and the yield of routine diagnostic tests for pneumonia was low. When bacterial coinfections did occur, Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae were the most common pathogens and atypical bacteria were rare. Although uncommon upon admission, bacterial infections frequently occurred in patients with prolonged hospitalization, and Pseudomonas aeruginosa, Klebsiella spp., and S. aureus were common pathogens. Antibacterial therapy and diagnostic testing for bacterial infections are unnecessary upon admission in most patients hospitalized with COVID-19, but clinicians should be vigilant for nosocomial bacterial infections.
Bacterial coinfections occur in <4% of patients who are hospitalized with COVID-19 and are usually caused by S. aureus, S. pneumoniae, and H. influenzae.Empirical antibacterial therapy and diagnostic testing for bacterial pathogens in patients hospitalized with COVID-19 are indicated only in those patients with critical illness, severe immunosuppression, radiographic findings suggestive of a bacterial pneumonia, or multiple laboratory parameters compatible with bacterial infection.Hospital-acquired infections are common among patients with prolonged hospitalization for COVID-19, and hospital-acquired pneumonia is most commonly caused by P. aeruginosa, Klebsiella spp., and S. aureus.Carbapenem-resistant Gram-negative infections are being increasingly reported in patients with COVID-19 requiring intensive care.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
The gut microbiome harbors a ‘silent reservoir’ of antibiotic resistance (AR) genes that is thought to contribute to the emergence of multidrug-resistant pathogens through horizontal gene ...transfer (HGT). To counteract the spread of AR, it is paramount to know which organisms harbor mobile AR genes and which organisms engage in HGT. Despite methods that characterize the overall abundance of AR genes in the gut, technological limitations of short-read sequencing have precluded linking bacterial taxa to specific mobile genetic elements (MGEs) encoding AR genes. Here, we apply Hi-C, a high-throughput, culture-independent method, to surveil the bacterial carriage of MGEs. We compare two healthy individuals with seven neutropenic patients undergoing hematopoietic stem cell transplantation, who receive multiple courses of antibiotics, and are acutely vulnerable to the threat of multidrug-resistant infections. We find distinct networks of HGT across individuals, though AR and mobile genes are associated with more diverse taxa within the neutropenic patients than the healthy subjects. Our data further suggest that HGT occurs frequently over a several-week period in both cohorts. Whereas most efforts to understand the spread of AR genes have focused on pathogenic species, our findings shed light on the role of the human gut microbiome in this process.
Abstract
Background
Patients hospitalized with coronavirus disease 2019 (COVID-19) frequently require mechanical ventilation and have high mortality rates. However, the impact of viral burden on ...these outcomes is unknown.
Methods
We conducted a retrospective cohort study of patients hospitalized with COVID-19 from 30 March 2020 to 30 April 2020 at 2 hospitals in New York City. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load was assessed using cycle threshold (Ct) values from a reverse transcription-polymerase chain reaction assay applied to nasopharyngeal swab samples. We compared characteristics and outcomes of patients with high, medium, and low admission viral loads and assessed whether viral load was independently associated with intubation and in-hospital mortality.
Results
We evaluated 678 patients with COVID-19. Higher viral load was associated with increased age, comorbidities, smoking status, and recent chemotherapy. In-hospital mortality was 35.0% (Ct <25; n = 220), 17.6% (Ct 25–30; n = 216), and 6.2% (Ct >30; n = 242) with high, medium, and low viral loads, respectively (P < .001). The risk of intubation was also higher in patients with a high viral load (29.1%) compared with those with a medium (20.8%) or low viral load (14.9%; P < .001). High viral load was independently associated with mortality (adjusted odds ratio aOR, 6.05; 95% confidence interval CI, 2.92–12.52) and intubation (aOR, 2.73; 95% CI, 1.68–4.44).
Conclusions
Admission SARS-CoV-2 viral load among hospitalized patients with COVID-19 independently correlates with the risk of intubation and in-hospital mortality. Providing this information to clinicians could potentially be used to guide patient care.
We evaluated 678 hospitalized patients with coronavirus disease 2019 and found that 35.0% of patients with a high severe acute respiratory syndrome coronavirus 2 viral load on admission died compared with 17.6% and 6.2% of patients with medium and low viral loads, respectively.
In this series of 393 consecutive patients admitted with Covid-19 to two New York City hospitals from March 3 to March 27, a third of patients received invasive mechanical ventilation, 10% of ...patients died, and 24% were still hospitalized as of April 10.
Polymyxins are relied upon for the treatment of carbapenem-resistant Gram-negative bacterial infections, but polymyxin resistance is increasing. Only broth microdilution is recommended for polymyxin ...susceptibility testing, but this method is impractical for most clinical microbiology laboratories. An article in this issue of the
(P. J. Simner, Y. Bergman, M. Trejo, A. A. Roberts, R. Marayan, T. Tekle, S. Campeau, A. Kazmi, D. Bell, S. Lewis, P. D. Tamma, R. Humphries, and J. A. Hindler, J Clin Microbiol 57:e01163-18, 2019, https://doi.org/10.1128/JCM.01163-18) found that colistin broth disk elution, a method that requires only colistin disks and broth, had excellent performance compared to broth microdilution for all strains except
-positive
strains.
Carbapenem-resistant Enterobacteriaceae (CRE) are emerging global pathogens. The spread of CRE to transplant recipients and patients with hematologic malignancies has ominous implications. These ...patients rely on timely, active antibacterial therapy to combat gram-negative infections; however, recommended empirical regimens are not active against CRE. Approximately 3%–10% of solid organ transplant (SOT) recipients in CRE-endemic areas develop CRE infection, and the infection site correlates with the transplanted organ. Mortality rates associated with CRE infections approach 40% in SOT recipients and 65% in patients with hematologic malignancies. Given that the current antimicrobial armamentarium to combat CRE is extremely limited, a multifaceted approach that includes antimicrobial stewardship and active surveillance is needed to prevent CRE infections in immunocompromised hosts. Improving outcomes of established infections will require the use of risk factor–based prediction tools and molecular assays to more rapidly administer CRE-active therapy and the development of new antimicrobial agents with activity against CRE.
Hematopoietic stem cell transplant (HSCT) recipients are uniquely threatened by the emergence of multidrug‐resistant (MDR) bacteria because these patients rely on immediate active antimicrobial ...therapy to combat bacterial infections. This review describes the epidemiology and treatment considerations for three challenging MDR bacterial pathogens in HSCT recipients: MDR Enterobacteriaceae, including extended‐spectrum β‐lactamase (ESBL)‐producing and carbapenem‐resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, and vancomycin‐resistant Enterococcus (VRE). These bacteria are common causes of infection in this population and bacteremias caused by these organisms are associated with high mortality rates. Carbapenems remain the treatments of choice for serious infections due to ESBL‐producing Enterobacteriaceae in HSCT recipients. Administration of β‐lactam agents as an extended infusion is associated with improved outcomes in patients with severe infections caused by P. aeruginosa. Older agents used for the treatment of CRE and MDR P. aeruginosa infections, such as polymyxins and aminoglycosides, have major limitations. Newer agents, such as ceftazidime‐avibactam and ceftolozane‐tazobactam have great potential for the treatment of Klebsiella pneumoniae carbapemenase‐producing CRE and MDR P. aeruginosa, respectively, but more pre‐clinical and clinical data are needed to better evaluate their efficacy. Daptomycin dosages ≥8 mg/kg/day are recommended to treat VRE infections in this population, particularly in the setting of increasing daptomycin resistance. Strategies to prevent these infections include strict adherence to recommended infection control practices and multidisciplinary antimicrobial stewardship. Last, gastrointestinal screening to guide empirical therapy and the use of polymerase chain reaction‐based rapid diagnostics may decrease the time to administration of appropriate therapy for these infections, thereby leading to improved outcomes.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
A surge of patients with coronavirus disease 2019 (COVID-19) presenting to New York City hospitals in March 2020 led to a sharp increase in blood culture utilization, which overwhelmed the capacity ...of automated blood culture instruments. We sought to evaluate the utilization and diagnostic yield of blood cultures during the COVID-19 pandemic to determine prevalence and common etiologies of bacteremia and to inform a diagnostic approach to relieve blood culture overutilization. We performed a retrospective cohort analysis of 88,201 blood cultures from 28,011 patients at a multicenter network of hospitals within New York City to evaluate order volume, positivity rate, time to positivity, and etiologies of positive cultures in COVID-19. Ordering volume increased by 34.8% in the second half of March 2020 compared to the level in the first half of the month. The rate of bacteremia was significantly lower among COVID-19 patients (3.8%) than among COVID-19-negative patients (8.0%) and those not tested (7.1%) (
< 0.001). COVID-19 patients had a high proportion of organisms reflective of commensal skin microbiota, which, when excluded, reduced the bacteremia rate to 1.6%. More than 98% of all positive cultures were detected within 4 days of incubation. Bloodstream infections are very rare for COVID-19 patients, which supports the judicious use of blood cultures in the absence of compelling evidence for bacterial coinfection. Clear communication with ordering providers is necessary to prevent overutilization of blood cultures during patient surges, and laboratories should consider shortening the incubation period from 5 days to 4 days, if necessary, to free additional capacity.
Recent data on polymyxin pharmacokinetics, pharmacodynamics, toxicity, and clinical outcomes suggest these agents have limited clinical utility. Pharmacokinetics-pharmacodynamics data show a ...steady-state concentration of 2 μg/mL is required for killing bacteria with colistin minimum inhibitory concentrations of 2 μg/mL. Less than 50% of patients with normal renal function achieve this exposure, and it is associated with high risk of nephrotoxicity. This exposure does not achieve bacterial stasis in pneumonia models. Randomized and observational studies consistently demonstrate increased mortality for polymyxins compared with alternative agents. The Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) are 2 global organizations that establish interpretive criteria for in vitro susceptibility data. CLSI has recently taken the step to eliminate the "susceptible" interpretive category for the polymyxins, whereas EUCAST maintains this interpretive category. This viewpoint describes the opinions of these organizations and the data that were used to inform their perspectives.
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