Ceftazidime-Avibactam (C/A) Resistant, Meropenem Sensitive KPC-Producing Klebsiella pneumoniae in ICU Setting: We Are What We Are Treated with?

The continuous spread of carbapenem-resistant Klebsiella pneumoniae (CP-Kp) strains presents a severe challenge to the healthcare system due to limited therapeutic options and high mortality. Since its availability, ceftazidime/avibactam (C/A) has become a first-line option against KPC-Kp, but C/A-resistant strains have been reported increasingly, especially with pneumonia or prior suboptimal blood exposure to C/A treatment. A retrospective, observational study was conducted with all patients admitted to the Intensive Care Unit (ICU) dedicated to COVID-19 patients at the City of Health & Sciences in Turin, between 1 May 2021 and 31 January 2022, with the primary endpoint to study strains with resistance to C/A, and secondly to describe the characteristics of this population, with or without previous exposure to C/A. Seventeen patients with colonization or invasive infection due to Klebsiella pneumoniae, C/A resistance, and susceptibility to meropenem (MIC = 2 µg/L) were included; the blaKPC genotype was detected in all isolates revealing D179Y mutation in the blaKPC-2 (blaKPC-33) gene. Cluster analysis showed that 16 out of the 17 C/A-resistant KPC-Kp isolates belonged to a single clone. Thirteen strains (76.5%) were isolated in a 60-day period. Only some patients had a previous infection with non-mutant KPC at other sites (5; 29.4%). Eight patients (47.1%) underwent previous large-spectrum antibiotic treatment, and four patients (23.5%) had prior treatment with C/A. The secondary spread of the D179Y mutation in the blaKPC-2 during the COVID-19 pandemic needs to be addressed constantly by an interdisciplinary interaction between microbiologists, infection control personnel, clinicians, and infectious diseases consultants to properly diagnose and treat patients.

Multidrug-Resistant Klebsiella pneumoniae in a Patient with SARS-Cov-2 Pneumonia in an Intensive Care Unit in Guayaquil, Ecuador: A Case Report.

BACKGROUND Multi-resistant microorganisms are a public health problem. Their incidence has risen due to COVID-19, indiscriminate antibiotics use, corticosteroid treatments, and higher admissions to intensive care units (ICUs) of patients requiring invasive mechanical ventilation. These are risk factors for bacterial over-infection. The present case study that is relevant because of the multiple isolated strains with a resistance pattern: Klebsiella pneumoniae carbapenemases (KPC), extended-spectrum beta lactamases (ESBL) and New Delhi metallo-ß-lactamase (NDM) in a patient without comorbidities. CASE REPORT A 53-year-old Ecuadorian man with no past medical history arrived at the Emergency Department (ED) with dyspnea, nasopharyngeal swab with a positive reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV2, and a chest computed tomography (CT) scan showing bilateral ground-glass pulmonary infiltrates with 40% involvement. On day 10 in the ICU, the presence of Klebsiella pneumoniae KPC strain was reported in an axillary swab culture. Consequently, the antibiotic was rotated to vancomycin 1 g intravenously (i.v.) every 12 h and meropenem 1 g i.v. every 8 h. On day 15 in the ICU, a tracheal secretion culture was reported with the presence of Klebsiella pneumoniae ESBL and a blood culture with Klebsiella pneumoniae NDM. CONCLUSIONS The COVID-19 pandemic is a perfect scenario for superinfection with multi-resistant pathogens such as carbapenem-resistant Klebsiella pneumoniae (CRKP), due to the increase in patients admitted to ICUs requiring invasive mechanical ventilation, the use of corticosteroids, and empirical broad-spectrum antibiotic management based on guidelines. The emergence of combined multidrug-resistant strains is a challenge for laboratory detection and the selection of antimicrobial treatment.

[Impact of SARS-COV-2 on the diagnosis of community bacteremia in a tertiary hospital]. / Impacto del SARS-CoV-2 en el diagnóstico de bacteriemia comunitaria en un hospital terciario.

OBJECTIVE: We carry out an analysis of the bacteremia diagnosed in the Emergency Department during 2020, coinciding with the period of the pandemic. METHODS: We performed a retrospective analysis from March 4, 2020 to December 31, 2020. RESULTS: The number of patients who went to the Emergency Department during the study period and the number of extracted blood cultures decreased by 46.79% and 35.7% compared to the same period in 2019 (p <0.05). 320 bacteremia occurred while 507 occurred in 2019, assuming a decrease of 36.8% (p <0.05). The positivity rate of blood cultures was 7.09% in 2020 and 7.23% in 2019 and the contamination rate was 7.07 % in 2020 and 5.67% in 2019. The most frequently isolated microorganism was Escherichia coli, followed by Staphylococcus aureus and Klebsiella pneumoniae. A 6.62% of the isolated E. coli were carriers of extended-spectrum beta-lactamases (ESBL). The percentage of methicillin-resistant S. aureus was 12.9 % and that of K. pneumoniae ESBL was 11.54%. CONCLUSIONS: During the SARS-CoV-2 pandemic there has been a decrease in the number of bacteremia diagnoses, it is possible that attention was focused especially on COVID, forgetting other diseases, such as bacteremia.

Interplay between Klebsiella pneumoniae producing KPC-31 and KPC-3 under treatment with high dosage meropenem: a case report.

The objective was to study ceftazidime-avibactam resistant and susceptible Klebsiella pneumoniae isolated from a patient admitted to the Policlinico Umberto I of Rome for SARS-CoV2. Data on the evolution of patient's conditions, antimicrobial therapies, and microbiological data were collected. Whole-genome sequencing performed by Illumina and Nanopore sequencing methods were used to type the strains. During the hospitalization, a SARS-CoV2-infected patient was colonized by a KPC-producing K. pneumoniae strain and empirically treated with ceftazidime-avibactam (CZA) when presenting spiking fever symptoms. Successively, ST2502 CZA-resistant strain producing the KPC-31 variant gave a pulmonary infection to the patient. The infection was treated with high doses of meropenem. The KPC-31-producing strain disappeared but the patient remained colonized by a KPC-3-producing K. pneumoniae strain. An interplay between highly conserved KPC-31- and KPC-3-producing ST2502 strains occurred in the SARS-CoV2 patient during the hospitalization, selected by CZA and carbapenem treatments, respectively.

Genetic Diversity, Antimicrobial Resistance Pattern, and Biofilm Formation in Klebsiella pneumoniae Isolated from Patients with Coronavirus Disease 2019 (COVID-19) and Ventilator-Associated Pneumonia.

INTRODUCTION: Patients with acute respiratory distress syndrome caused by coronavirus disease 2019 (COVID-19) are at risk for superadded infections, especially infections caused by multidrug resistant (MDR) pathogens. Before the COVID-19 pandemic, the prevalence of MDR infections, including infections caused by MDR Klebsiella pneumoniae (K. pneumoniae), was very high in Iran. This study is aimed at assessing the genetic diversity, antimicrobial resistance pattern, and biofilm formation in K. pneumoniae isolates obtained from patients with COVID-19 and ventilator-associated pneumonia (VAP) hospitalized in an intensive care unit (ICU) in Iran. METHODS: In this cross-sectional study, seventy K. pneumoniae isolates were obtained from seventy patients with COVID-19 hospitalized in the ICU of Shahid Beheshti hospital, Kashan, Iran, from May to September, 2020. K. pneumoniae was detected through the ureD gene. Antimicrobial susceptibility testing was done using the Kirby-Bauer disc diffusion method, and biofilm was detected using the microtiter plate assay method. Genetic diversity was also analyzed through polymerase chain reaction based on enterobacterial repetitive intergenic consensus (ERIC-PCR). The BioNumerics software (v. 8.0, Applied Maths, Belgium) was used for analyzing the data and drawing dendrogram and minimum spanning tree. Findings. K. pneumoniae isolates had varying levels of resistance to antibiotics meropenem (80.4%), cefepime-aztreonam-piperacillin/tazobactam (70%), tobramycin (61.4%), ciprofloxacin (57.7%), gentamicin (55.7%), and imipenem (50%). Around 77.14% of isolates were MDR, and 42.8% of them formed biofilm. Genetic diversity analysis revealed 28 genotypes (E1-E28) and 74.28% of isolates were grouped into ten clusters (i.e., clusters A-J). Clusters were further categorized into three major clusters, i.e., clusters E, H, and J. Antimicrobial resistance to meropenem, tobramycin, gentamicin, and ciprofloxacin in cluster J was significantly higher than cluster H, denoting significant relationship between ERIC clusters and antimicrobial resistance. However, there was no significant difference among major clusters E, H, and J respecting biofilm formation. CONCLUSION: K. pneumoniae isolates obtained from patients with COVID-19 have high antimicrobial resistance, and 44.2% of them have genetic similarity and can be clustered in three major clusters. There is a significant difference among clusters respecting antimicrobial resistance.

ENDOGENOUS ENDOPHTHALMITIS IN THE SETTING OF COVID-19 INFECTION: A Case Series.

PURPOSE: To describe endogenous endophthalmitis in the setting of COVID-19 pneumonia. METHODS: Patients recovering from COVID-19 pneumonia who presented to our department with any or all of the following complaints: pain, watering, redness, and decreased vision were identified. All relevant data were collected for analysis. RESULTS: Three patients with endogenous endophthalmitis were identified. All patients had been treated for COVID-19 pneumonia and therefore had received remdesivir and systemic steroids; 2 of the 3 patients received tocilizumab. All patients received vitreous biopsy, vitrectomy, and intraocular antibiotic injection. Patient 1 demonstrated Klebsiella pneumoniae in blood culture, K. pneumoniae and Escherichia coli in urine culture, and K. pneumoniae in vitreous fluid, whereas Patients 2 and 3 demonstrated Stenotrophomonas maltophilia and methicillin-resistant Staphylococcus aureus in the blood and nasopharyngeal culture, respectively. Correspondingly, the same organism was cultured from vitreous in Patients 2 and 3. The visual acuity at the last follow-up in Patients 1 to 3 was 20/100, 20/80, and 20/40, respectively. The probable source of infection was identified in each as renal calculi, dental caries, and the pharynx, respectively. Real-time polymerase chain reaction demonstrated the presence of Severe Acute Respiratory Syndrome Coronavirus 2 in the vitreous fluid of Patient 1. CONCLUSION: We report good outcomes of early intervention for endogenous endophthalmitis in the setting of COVID-19 infection. We also document the presence of SARS-CoV-2 in vitreous.

Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience.

Background: The aim of this study was to assess the drivers of multidrug-resistant (MDR) bacterial infection development in coronavirus disease 2019 (COVID-19) and its impact on patient outcome. Methods: Retrospective analysis on data from 32 consecutive patients with COVID-19, admitted to our intensive care unit (ICU) from March to May 2020. Outcomes considered were MDR infection and ICU mortality. Results: Fifty percent of patients developed an MDR infection during ICU stay after a median time of 8 [4-11] days. Most common MDR pathogens were carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, causing bloodstream infections and pneumonia. MDR infections were linked to a higher length of ICU stay (p = 0.002), steroid therapy (p = 0.011), and associated with a lower ICU mortality (odds ratio: 0.439, 95% confidence interval: 0.251-0.763; p < 0.001). Low-dose aspirin intake was associated with both MDR infection (p = 0.043) and survival (p = 0.015). Among MDR patients, mortality was related with piperacillin-tazobactam use (p = 0.035) and an earlier onset of MDR infection (p = 0.042). Conclusions: MDR infections were a common complication in critically ill COVID-19 patients at our center. MDR risk was higher among those dwelling longer in the ICU and receiving steroids. However, MDR infections were not associated with a worse outcome.

Rare case of endogenous Klebsiella endophthalmitis associated with emphysematous prostatitis in a patient with diabetes, cirrhosis and COVID-19.

A 35-year-old Hispanic man presented with fever, chills, dysuria, diarrhoea, scleral icterus, tachycardia and tachypnea. He was found to be COVID-19 positive, CT of the pelvis revealed prostatic abscess, and urine culture grew Klebsiella pneumoniae Additionally, he was found to have diabetes and cirrhosis. During treatment, the patient developed vision loss, and was diagnosed with endogenous Klebsiella endophthalmitis. The patient was treated with intravenous antibiotics, pars plana vitrectomy, intravitreal antibiotics and cystoscopy/suprapubic catheter placement. On follow-up, the patient has had the suprapubic catheter removed, and successfully passed a voiding trial, but suffers permanent vision loss in both eyes.

Spread of OXA-48-producing Klebsiella pneumoniae among COVID-19-infected patients: The storm after the storm.

The impact of secondary infections by multidrug-resistant bacteria in COVID-19- infected patients has yet to be evaluated. Here, we report the clinical and molecular features of an outbreak of seven patients carrying CTX-M-15- and OXA-48-producing Klebsiella pneumoniae belonging to ST326 during COVID-19 pandemic in an ICU in northern Spain. Those patients were admitted to beds close to each other, two of them developed ventilator-associated pneumonia (VAP), one exhibited primary bacteremia and the remaining four were considered to be colonized. None of them was colonized prior to admission to the ICU an all, except one of those who developed VAP, were discharged. Hydroxychloroquine and lopinavir/ritonavir were administered to all of them as COVID-19 therapy and additionally, three of them received tocilizumab and corticosteroids, respectively. Reusing of personal protective equipment due to its initial shortage, relaxation in infection control measures and negative-pressure air in ICU rooms recommended for the protection of health care workers (HCWs), could have contributed to this outbreak. Maximization of infection control measures is essential to avoid secondary infections by MDR bacteria in COVID-infected patients.

Rates of bacterial co-infections and antimicrobial use in COVID-19 patients: a retrospective cohort study in light of antibiotic stewardship.

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.

Antiviral activity of the high-molecular-weight plant polysaccharides (Panavir®).

This short report is dedicated to the description of the wide antiviral and antibacterial activity of the immune-modulating agent Panavir®. Panavir® is a high-molecular-weight fraction of the polysaccharides extracted from the shoots of the Solanum tuberosum. It demonstrates activity against many types of viruses, including animal coronavirus and also against bacterial infections. These properties look very promising considering the COVID-19 epidemy and allow propose that Panavir® would be effective in the therapy of the SARS-CoV-2 infection.