Gearing up for battle: Harnessing adaptive T cell immunity against gram-negative pneumonia.

Pneumonia is one of the leading causes of morbidity and mortality worldwide and Gram-negative bacteria are a major cause of severe pneumonia. Despite advances in diagnosis and treatment, the rise of multidrug-resistant organisms and hypervirulent strains demonstrates that there will continue to be challenges with traditional treatment strategies using antibiotics. Hence, an alternative approach is to focus on the disease tolerance components that mediate immune resistance and enhance tissue resilience. Adaptive immunity plays a pivotal role in modulating these processes, thus affecting the incidence and severity of pneumonia. In this review, we focus on the adaptive T cell responses to pneumonia induced by Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. We highlight key factors in these responses that have potential for therapeutic targeting, as well as the gaps in current knowledge to be focused on in future work.

Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set.

BACKGROUND: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients. METHODS: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method. RESULTS: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO. CONCLUSIONS: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021).

Severe Recurrent Bacterial Pneumonia Among Children Living With HIV.

BACKGROUND: Bacterial pneumonia imparts a major morbidity and mortality burden on children living with HIV, yet effective prevention and treatment options are underutilized. We explored clinical factors associated with severe recurrent bacterial pneumonia among children living with HIV. METHODS: Children enrolled in the TREAT Asia Pediatric HIV Observational Database were included if they started antiretroviral therapy (ART) on or after January 1st, 2008. Factors associated with severe recurrent bacterial pneumonia were assessed using competing-risk regression. RESULTS: A total of 3,944 children were included in the analysis; 136 cases of severe recurrent bacterial pneumonia were reported at a rate of 6.5 [95% confidence interval (CI): 5.5-7.7] events per 1,000 patient-years. Clinical factors associated with severe recurrent bacterial pneumonia were younger age [adjusted subdistribution hazard ratio (aHR): 4.4 for <5 years versus ≥10 years, 95% CI: 2.2-8.4, P < 0.001], lower weight-for-age z-score (aHR: 1.5 for <-3.0 versus >-2.0, 95% CI: 1.1-2.3, P = 0.024), pre-ART diagnosis of severe recurrent bacterial pneumonia (aHR: 4.0 versus no pre-ART diagnosis, 95% CI: 2.7-5.8, P < 0.001), past diagnosis of symptomatic lymphoid interstitial pneumonitis or chronic HIV-associated lung disease, including bronchiectasis (aHR: 4.8 versus no past diagnosis, 95% CI: 2.8-8.4, P < 0.001), low CD4% (aHR: 3.5 for <10% versus ≥25%, 95% CI: 1.9-6.4, P < 0.001) and detectable HIV viral load (aHR: 2.6 versus undetectable, 95% CI: 1.2-5.9, P = 0.018). CONCLUSIONS: Children <10-years-old and those with low weight-for-age, a history of respiratory illness, low CD4% or poorly controlled HIV are likely to gain the greatest benefit from targeted prevention and treatment programs to reduce the burden of bacterial pneumonia in children living with HIV.

Utilisation of antimicrobials used to treat bacterial pneumonia in principal referral hospitals during the COVID-19 pandemic, Australia, 2020.

BACKGROUND: Concerns have been raised internationally, regarding possible increased antimicrobial use during the COVID-19 pandemic and the potential impact on antimicrobial resistance. This analysis aimed to investigate hospital usage rates of broad-spectrum antibacterial agents used to treat community-acquired pneumonia (CAP) and/or hospital-acquired pneumonia (HAP) in Australian principal referral hospitals during 2020. Secondly, usage rates in Victoria were compared with equivalent national rates. METHODS: Monthly antimicrobial dispensing data for all 31 Australian principal referral hospitals were analysed for the period January 2019 to December 2020. Grams of antimicrobial agents used were converted into the World Health Organization (WHO) assigned metric 'Defined Daily Dose' (DDD). Using the hospital activity metric Occupied Bed Days (OBD), a standardised usage density rate was calculated (in units of DDD / 1,000 OBD). RESULTS: The typical expected seasonal trend in aggregate usage rates, for antibacterials used in the treatment of CAP, was not evident in 2020. Overall usage of doxycycline, azithromycin, amoxicillin and cefuroxime decreased in principal referral hospitals compared to 2019. Aggregated monthly usage rates for broad-spectrum agents used to treat HAP increased nationally, on average, by 5.0% in 2020 compared to 2019. Victoria's second COVID-19 wave (July-October 2020) coincided with higher usage rates of antibacterials used for CAP. CONCLUSION: Public health interventions introduced to limit the spread of SARS-CoV-2 infections may have had unintended benefits on other respiratory infection rates. The drop in hospital usage of antibacterials typically used to treat CAP suggests that the number of cases of pneumonia acquired in the community requiring hospitalisation was markedly reduced in 2020.

Recombinant Myeloperoxidase as a New Class of Antimicrobial Agents.

Heme-containing peroxidases are widely distributed in the animal and plant kingdoms and play an important role in host defense by generating potent oxidants. Myeloperoxidase (MPO), the prototype of heme-containing peroxidases, exists in neutrophils and monocytes. MPO has a broad spectrum of microbial killing. The difficulty of producing MPO at a large scale hinders its study and utilization. This study aimed to overexpress recombinant human MPO and characterize its microbicidal activities in vitro and in vivo. A human HEK293 cell line stably expressing recombinant MPO (rMPO) was established as a component of this study. rMPO was overexpressed and purified for studies on its biochemical and enzymatic properties, as well as its microbicidal activities. In this study, rMPO was secreted into culture medium as a monomer. rMPO revealed enzymatic activity similar to that of native MPO. rMPO, like native MPO, was capable of killing a broad spectrum of microorganisms, including Gram-negative and -positive bacteria and fungi, at low nM levels. Interestingly, rMPO could kill antibiotic-resistant bacteria, making it very useful for treatment of nosocomial infections and mixed infections. The administration of rMPO significantly reduced the morbidity and mortality of murine lung infections induced by Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. In animal safety tests, the administration of 100 nM rMPO via tail vein did not result in any sign of toxic effects. Taken together, the data suggest that rMPO purified from a stably expressing human cell line is a new class of antimicrobial agents with the ability to kill a broad spectrum of pathogens, including bacteria and fungi with or without drug resistance. IMPORTANCE Over the past 2 decades, more than 20 new infectious diseases have emerged. Unfortunately, novel antimicrobial therapeutics are discovered at much lower rates. Infections caused by resistant microorganisms often fail to respond to conventional treatment, resulting in prolonged illness, greater risk of death, and high health care costs. Currently, this is best seen with the lack of a cure for coronavirus disease 2019 (COVID-19). To combat such untreatable microorganisms, there is an urgent need to discover new classes of antimicrobial agents. Myeloperoxidase (MPO) plays an important role in host defense. The difficulty of producing MPO on a large scale hinders its study and utilization. We have produced recombinant MPO at a large scale and have characterized its antimicrobial activities. Most importantly, recombinant MPO significantly reduced the morbidity and mortality of murine pneumonia induced by Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. Our data suggest that recombinant MPO from human cells is a new class of antimicrobials with a broad spectrum of activity.

Diagnosis and Treatment of Bacterial Pneumonia in Critically Ill Patients with COVID-19 Using a Multiplex PCR Assay: A Large Italian Hospital's Five-Month Experience.

Bacterial pneumonia is a challenging coronavirus disease 2019 (COVID-19) complication for intensive care unit (ICU) clinicians. Upon its implementation, the FilmArray pneumonia plus (FA-PP) panel's practicability for both the diagnosis and antimicrobial therapy management of bacterial pneumonia was assessed in ICU patients with COVID-19. Respiratory samples were collected from patients who were mechanically ventilated at the time bacterial etiology and antimicrobial resistance were determined using both standard-of-care (culture and antimicrobial susceptibility testing [AST]) and FA-PP panel testing methods. Changes to targeted and/or appropriate antimicrobial therapy were reviewed. We tested 212 samples from 150 patients suspected of bacterial pneumonia. Etiologically, 120 samples were positive by both methods, two samples were culture positive but FA-PP negative (i.e., negative for on-panel organisms), and 90 were negative by both methods. FA-PP detected no culture-growing organisms (mostly Staphylococcus aureus or Pseudomonas aeruginosa) in 19 of 120 samples or antimicrobial resistance genes in two culture-negative samples for S. aureus organisms. Fifty-nine (27.8%) of 212 samples were from empirically treated patients. Antibiotics were discontinued in 5 (33.3%) of 15 patients with FA-PP-negative samples and were escalated/deescalated in 39 (88.6%) of 44 patients with FA-PP-positive samples. Overall, antibiotics were initiated in 87 (72.5%) of 120 pneumonia episodes and were not administered in 80 (87.0%) of 92 nonpneumonia episodes. Antimicrobial-resistant organisms caused 78 (60.0%) of 120 episodes. Excluding 19 colistin-resistant Acinetobacter baumannii episodes, AST confirmed appropriate antibiotic receipt in 101 (84.2%) of 120 episodes for one or more FA-PP-detected organisms. Compared to standard-of-care testing, the FA-PP panel may be of great value in the management of COVID-19 patients at risk of developing bacterial pneumonia in the ICU. IMPORTANCE Since bacterial pneumonia is relatively frequent, suspicion of it in COVID-19 patients may prompt ICU clinicians to overuse (broad-spectrum) antibiotics, particularly when empirical antibiotics do not cover the suspected pathogen. We showed that a PCR-based, culture-independent laboratory assay allows not only accurate diagnosis but also streamlining of antimicrobial therapy for bacterial pneumonia episodes. We report on the actual implementation of rapid diagnostics and its real-life impact on patient treatment, which is a gain over previously published studies on the topic. A better understanding of the role of that or similar PCR assays in routine ICU practice may lead us to appreciate the effectiveness of their implementation during the COVID-19 pandemic.

An AI-based auxiliary empirical antibiotic therapy model for children with bacterial pneumonia using low-dose chest CT images.

PURPOSE: To construct an auxiliary empirical antibiotic therapy (EAT) multi-class classification model for children with bacterial pneumonia using radiomics features based on artificial intelligence and low-dose chest CT images. MATERIALS AND METHODS: Data were retrospectively collected from children with pathogen-confirmed bacterial pneumonia including Gram-positive bacterial pneumonia (122/389, 31%), Gram-negative bacterial pneumonia (159/389, 41%) and atypical bacterial pneumonia (108/389, 28%) from January 1 to June 30, 2019. Nine machine-learning models were separately evaluated based on radiomics features extracted from CT images; three optimal submodels were constructed and integrated to form a multi-class classification model. RESULTS: We selected five features to develop three radiomics submodels: a Gram-positive model, a Gram-negative model and an atypical model. The comprehensive radiomics model using support vector machine method yielded an average area under the curve (AUC) of 0.75 [95% confidence interval (CI), 0.65-0.83] and accuracy (ACC) of 0.58 [sensitivity (SEN), 0.57; specificity (SPE), 0.78] in the training set, and an average AUC of 0.73 (95% CI 0.61-0.79) and ACC of 0.54 (SEN, 0.52; SPE, 0.75) in the test set. CONCLUSION: This auxiliary EAT radiomics multi-class classification model was deserved to be researched in differential diagnosing bacterial pneumonias in children.

Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19.

Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin signaling. Dexamethasone during severe COVID-19 affected circulating neutrophils, altered IFNactive neutrophils, downregulated interferon-stimulated genes and activated IL-1R2+ neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFNactive neutrophils and preferential steroid-induced immature neutrophil expansion, potentially affecting outcomes. Our single-cell atlas (see 'Data availability' section) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.

Reducing the use of empiric antibiotic therapy in COVID-19 on hospital admission.

BACKGROUND: Empiric antibiotics for community acquired bacterial pneumonia (CABP) are often prescribed to patients with COVID-19, despite a low reported incidence of co-infections. Stewardship interventions targeted at facilitating appropriate antibiotic prescribing for CABP among COVID-19 patients are needed. We developed a guideline for antibiotic initiation and discontinuation for CABP in COVID-19 patients. The purpose of this study was to assess the impact of this intervention on the duration of empiric CABP antibiotic therapy among patients with COVID-19. METHODS: This was a single-center, retrospective, quasi-experimental study of adult patients admitted between 3/1/2020 to 4/25/2020 with COVID-19 pneumonia, who were initiated on empiric CABP antibiotics. Patients were excluded if they were initiated on antibiotics > 48 h following admission or if another source of infection was identified. The primary outcome was the duration of antibiotic therapy (DOT) prior to the guideline (March 1 to March27, 2020) and after guideline implementation (March 28 to April 25, 2020). We also evaluated the clinical outcomes (mortality, readmissions, length of stay) among those initiated on empiric CABP antibiotics. RESULTS: A total of 506 patients with COVID-19 were evaluated, 102 pre-intervention and 404 post-intervention. Prior to the intervention, 74.5% (n = 76) of patients with COVID-19 received empiric antibiotics compared to only 42% of patients post-intervention (n = 170), p < 0.001. The median DOT in the post-intervention group was 1.3 days shorter (p < 0.001) than the pre-intervention group, and antibiotics directed at atypical bacteria DOT was reduced by 2.8 days (p < 0.001). More patients in the post-intervention group were initiated on antibiotics based on criteria consistent with our guideline (68% versus 87%, p = 0.001). There were no differences between groups in terms of clinical outcomes. CONCLUSION: Following the implementation of a guideline outlining recommendations for initiating and discontinuing antibiotics for CABP among COVID-19 inpatients, we observed a reduction in antibiotic prescribing and DOT. The guideline also resulted in a significant increase in the rate of guideline-congruent empiric antibiotic initiation.

Diagnostic value of using a combination of nucleic acid and specific antibody tests for SARS-CoV-2 in coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) is a newly emerged disease with various clinical manifestations and imaging features. The diagnosis of COVID-19 depends on a positive nucleic acid amplification test by real-time reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the clinical manifestations and imaging features of COVID-19 are non-specific, and nucleic acid test for SARS-CoV-2 can have false-negative results. It is presently believed that detection of specific antibodies to SARS-CoV-2 is an effective screening and diagnostic indicator for SARS-CoV-2 infection. Thus, a combination of nucleic acid and specific antibody tests for SARS-CoV-2 will be more effective to diagnose COVID-19, especially to exclude suspected cases.

Detection of Viruses by Multiplex Real-Time Polymerase Chain Reaction in Bronchoalveolar Lavage Fluid of Patients with Nonresponding Community-Acquired Pneumonia.

Background: Nonresponding pneumonia is responsible for the most mortality of community-acquired pneumonia (CAP). However, thus far, it is not clear whether viral infection plays an important role in the etiology of nonresponding CAP and whether there is a significant difference in the clinical characteristics between viral and nonviral nonresponding CAP. Methods: From 2016 to 2019, nonresponding CAP patients were retrospectively enrolled in our study. All patients received bronchoalveolar lavage (BAL) and virus detection in BAL fluid by multiplex real-time polymerase chain reaction (PCR), and clinical, laboratory, and radiographic data were collected. Results: A total of 43 patients were included. The median age was 62 years, and 65.1% of patients were male. Overall, 20 patients (46.5%) were identified with viral infection. Of these viruses, influenza virus (n = 8) and adenovirus (n = 7) were more frequently detected, and others included herpes simplex virus, human enterovirus, cytomegalovirus, human coronavirus 229E, rhinovirus, and parainfluenza virus. Compared with nonviral nonresponding CAP, only ground-glass opacity combined with consolidation was a more common imaging manifestation in viral nonresponding CAP. However, no obvious differences were found in clinical and laboratory findings between the presence and the absence of viral infections. Conclusions: Viral infections were particularly frequent in adults with nonresponding CAP. The ground-glass opacity combined with consolidation was a specific imaging manifestation for viral nonresponding CAP, while the clinical and laboratory data showed no obvious differences between viral and nonviral nonresponding CAP.

Co-morbidity of Covid-19 and Stenotrophomonas maltophilia in a Patient with Hodgkin's Lymphoma History from North of Iran.

INTRODUCTION: Immunocompromised patients, especially those hospitalized, are at a higher risk for infection with opportunistic pathogens such as Stenotrophomonas maltophilia (S. maltophilia) which is a multidrug-resistant gram-negative bacillus and can cause a challenge in the management of patients with concomitant COVID-19 and S. maltophilia pneumonia. CASE PRESENTATION: A 71-year-old man with Hodgkin's lymphoma presented with severe respiratory symptoms of COVID-19 was intubated upon admission and the initial standard treatment for COVID-19 was started for him. The patient subsequently developed superimposed bacterial pneumonia with S. maltophilia. According to that, the patient's intubation tube was removed and a tracheostomy was performed for him. Also, antibiotic treatment was replaced with Colistin and Co-trimoxazole drugs. Finally, after 31 days of hospitalization in the ICU and the appropriate drug treatment, he was discharged with reduced symptoms and partial recovery. CONCLUSION: It should be noted that the occurrence of co-infection with multidrug-resistant pathogens such as S. maltophilia requires proper management to select appropriate treatment methods and drugs, so that in addition to proper effectiveness, it does not lead to side effects and complications associated with COVID-19 disease.

Recommendations for antibacterial therapy in adults with COVID-19 - an evidence based guideline.

SCOPE: The Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19). METHODS: We performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology. QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: We assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic.

Uninterrupted Continuous and Intermittent Nebulizer Therapy in a COVID-19 Patient Using Sequential Vibratory Mesh Nebulizers: A Case Report.

Interruptions in continuous nebulized pulmonary vasodilators, such as epoprostenol, can potentially result in clinical deterioration in respiratory status. Coadministration of other intermittent nebulized therapies may require opening the ventilator circuit to facilitate administration. However, in patients with SARS-CoV2 infection, it is preferred to avoid opening the circuit whenever feasible to prevent aerosolization of the virus and exposure of health care workers. In this study, we describe a unique method of administering continuous epoprostenol nebulization and intermittent nebulized antibiotics, mucolytics, and bronchodilators, using Aerogen vibrating mesh nebulizers without interruptions in epoprostenol or opening the ventilator circuit. This technique set up consisted of stacking two Aerogen nebulizer cups, each with its own controller. This approach was successful in allowing concomitant delivery of intermittent and continuous nebulized therapy without interruptions. To our knowledge, this method has not been previously described in the literature and may be helpful to bedside clinicians facing a similar clinical scenario.

Renal Transplant Recipient with Concurrent COVID-19 and Stenotrophomonas maltophilia Pneumonia Treated with Trimethoprim/Sulfamethoxazole Leading to Acute Kidney Injury: A Therapeutic Dilemma.

BACKGROUND Although coronavirus disease 2019 (COVID-19) manifests primarily as a lung infection, its involvement in acute kidney injury (AKI) is gaining recognition and is associated with increased morbidity and mortality. Concurrent infection, which may require administration of a potentially nephrotoxic agent, can worsen AKI and lead to poor outcomes. Stenotrophomonas maltophilia is a multidrug-resistant gram-negative bacillus associated with nosocomial infections, especially in severely immunocompromised and debilitated patients. Trimethoprim/sulfamethoxazole combination (TMP/SMX) is considered the treatment of choice but can itself lead to AKI, posing a significant challenge in the management of patients with concomitant COVID-19 and S. maltophilia pneumonia. CASE REPORT A 64-year-old male with end-stage renal disease and post renal transplant presented with severe respiratory symptoms of COVID-19 and was intubated upon admission. His renal functions were normal at the time of admission. The patient subsequently developed superimposed bacterial pneumonia with S. maltophilia requiring administration of TMP/SMX. However, TMP/SMX led to the development of AKI, which continued to worsen despite appropriate management including hemodialysis. This coincided with and most likely resulted in the patient's clinical deterioration and ultimate death. CONCLUSIONS The etiology of kidney disease involvement in patients with COVID-19 is still evolving and appears to be multifactorial. The condition can significantly worsen especially when nephrotoxic agents are given, probably due to a cumulative or synergistic effect. Great caution should be taken when administering nephrotoxic agents in the setting of COVID-19 as it can lead to adverse patient outcomes.

Bacterial co-infections with SARS-CoV-2.

The pandemic coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide. To date, there are no proven effective therapies for this virus. Efforts made to develop antiviral strategies for the treatment of COVID-19 are underway. Respiratory viral infections, such as influenza, predispose patients to co-infections and these lead to increased disease severity and mortality. Numerous types of antibiotics such as azithromycin have been employed for the prevention and treatment of bacterial co-infection and secondary bacterial infections in patients with a viral respiratory infection (e.g., SARS-CoV-2). Although antibiotics do not directly affect SARS-CoV-2, viral respiratory infections often result in bacterial pneumonia. It is possible that some patients die from bacterial co-infection rather than virus itself. To date, a considerable number of bacterial strains have been resistant to various antibiotics such as azithromycin, and the overuse could render those or other antibiotics even less effective. Therefore, bacterial co-infection and secondary bacterial infection are considered critical risk factors for the severity and mortality rates of COVID-19. Also, the antibiotic-resistant as a result of overusing must be considered. In this review, we will summarize the bacterial co-infection and secondary bacterial infection in some featured respiratory viral infections, especially COVID-19.