Special Issue "Diagnosis and Treatment of Pneumonia"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pulmonology".

Deadline for manuscript submissions: 31 December 2019.

Special Issue Editor

Prof. Dr. Antoni Torres
E-Mail Website
Guest Editor
Director Pulmonary Intensive Care Unit, Respiratory Institute, Hospital Clinic of Barcelona
Interests: respiratory medicine; epidemiology; risk factors; outcome; treatment; prevention and pathogenetic mechanisms of respiratory infections; community-acquired pneumonia; intensive care
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Pneumonia is a severe health problem and a significant cause of mortality and morbidity worldwide. The burden of pneumonia is expected to grow given the increasing aging population, the number of patients with multiple comorbidities, including immunosuppression, and the emergence of antibiotic resistance pathogens. PES pathogens (Pseudomonas aeruginosa, extended-spectrum β-lactamase Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus) account for approximately 6% of cases of community-acquired pneumonia (CAP) with microbiological diagnosis. Multidrug-resistant (MDR) pathogens account for approximately half of the microbiologically confirmed cases of ventilator-associated pneumonia (VAP).

Despite improvements in its management, due to the implementation of international guidelines for community-acquired, hospital-acquired, and ventilator-associated pneumonia, the diagnosis of pneumonia is still a challenge, especially in specific populations, such as elderly patients and immunocompromised patients. Our current clinical practice is insufficient to reduce the associated morbidity and mortality rates, as well as to avoid short- and long-term sequelae. There is a need for novel approaches to be incorporated in the clinical practice, embracing new knowledge, prevention measures, and therapeutic strategies.

Prof. Dr. Antoni Torres
Guest Editor

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Keywords

  • pneumonia
  • community-acquired pneumonia
  • hospital-acquired pneumonia
  • ventilator-associated pneumonia
  • diagnosis
  • therapy
  • management
  • respiratory infections

Published Papers (11 papers)

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Research

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Open AccessArticle
Clinical Factors Associated with a Shorter or Longer Course of Antibiotic Treatment in Patients with Exacerbations of Bronchiectasis: A Prospective Cohort Study
J. Clin. Med. 2019, 8(11), 1950; https://doi.org/10.3390/jcm8111950 (registering DOI) - 12 Nov 2019
Abstract
Background: Bronchiectasis exacerbations are often treated with prolonged antibiotic use, even though there is limited evidence for this approach. We therefore aimed to investigate the baseline clinical and microbiological findings associated with long courses of antibiotic treatment in exacerbated bronchiectasis patients. Methods: This [...] Read more.
Background: Bronchiectasis exacerbations are often treated with prolonged antibiotic use, even though there is limited evidence for this approach. We therefore aimed to investigate the baseline clinical and microbiological findings associated with long courses of antibiotic treatment in exacerbated bronchiectasis patients. Methods: This was a bi-centric prospective observational study of bronchiectasis exacerbated adults. We compared groups receiving short (≤14 days) and long (15–21 days) courses of antibiotic treatment. Results: We enrolled 191 patients (mean age 72 (63, 79) years; 108 (56.5%) females), of whom 132 (69%) and 59 (31%) received short and long courses of antibiotics, respectively. Multivariable logistic regression of the baseline variables showed that long-term oxygen therapy (LTOT), moderate–severe exacerbations, and microbiological isolation of Pseudomonas aeruginosa were associated with long courses of antibiotic therapy. When we excluded patients with a diagnosis of community-acquired pneumonia (n = 49), in the model we found that an etiology of P. aeruginosa remained as factor associated with longer antibiotic treatment, with a moderate and a severe FACED score and the presence of arrhythmia as comorbidity at baseline. Conclusions: Decisions about the duration of antibiotic therapy should be guided by clinical and microbiological assessments of patients with infective exacerbations. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Pneumonia)
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Open AccessArticle
Predictors and Clinical Outcomes in Empyema Thoracis Patients Presenting to the Emergency Department Undergoing Video-Assisted Thoracoscopic Surgery
J. Clin. Med. 2019, 8(10), 1612; https://doi.org/10.3390/jcm8101612 - 03 Oct 2019
Abstract
Background: Video-assisted thoracoscopic surgery (VATS) is widely used for the treatment of empyema. We evaluated clinical symptoms, laboratory examinations, and thoracentesis to assess patients in the emergency department (ED) with empyema thoracis, undergoing VATS to identify predictors of adverse outcomes. Methods: This retrospective [...] Read more.
Background: Video-assisted thoracoscopic surgery (VATS) is widely used for the treatment of empyema. We evaluated clinical symptoms, laboratory examinations, and thoracentesis to assess patients in the emergency department (ED) with empyema thoracis, undergoing VATS to identify predictors of adverse outcomes. Methods: This retrospective study was conducted by reviewing records of ED patients with pleural empyema admitted for VATS from January 2007 to June 2014. Demographic data, clinical symptoms, and laboratory examinations were compared for survivors (Group I) and non-survivors (Group II). Logistic regression analysis was used to identify parameters related to postoperative mortality. Results: From 380 patients, 7.6% (n = 29) died postoperatively. Survivors and non-survivors exhibited differences in age, gender, presence of cough, dyspnea, chest pain, empyema stage, cerebrovascular disease, malignancy, the glucose level of pleural fluid, serum hemoglobin, platelet count, blood urea nitrogen, and potassium levels. The logistic analysis demonstrated that the most significant factor related to the postoperative morbidity is chest pain (p = 0.018). Conclusions: VATS could be a safe option for pediatric and geriatric patients. Age does not appear to affect postoperative mortality. A high degree of awareness is essential for perioperative management and early surgical treatment when ED patients present with the clinical symptom of chest pain. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Pneumonia)
Open AccessCommunication
Effect of Corticosteroids on C-Reactive Protein in Patients with Severe Community-Acquired Pneumonia and High Inflammatory Response: The Effect of Lymphopenia
J. Clin. Med. 2019, 8(9), 1461; https://doi.org/10.3390/jcm8091461 - 13 Sep 2019
Abstract
Background: Lymphopenic patients with community-acquired pneumonia (CAP) have shown high mortality rates. Corticosteroids have immunomodulatory properties and regulate cytokine storm in CAP. However, it is not known whether their modulatory effect on cytokine secretion differs in lymphopenic and non-lymphopenic patients with CAP. Therefore, [...] Read more.
Background: Lymphopenic patients with community-acquired pneumonia (CAP) have shown high mortality rates. Corticosteroids have immunomodulatory properties and regulate cytokine storm in CAP. However, it is not known whether their modulatory effect on cytokine secretion differs in lymphopenic and non-lymphopenic patients with CAP. Therefore, we aimed to test whether the presence of lymphopenia may modify the response to corticosteroids (mainly in C reactive protein (CRP)) in patients with severe CAP and high inflammatory status). Methods: A post hoc analysis of a randomized controlled trial (NCT00908713) which evaluated the effect of corticosteroids in patients with severe CAP and high inflammatory response (CRP > 15 mg/dL). Patients were clustered according to the presence of lymphopenia (lymphocyte count below 1000 cell/mm3). Results: At day 1, 35 patients (59%) in the placebo group presented with lymphopenia, compared to 44 patients (73%) in the corticosteroid group. The adjusted mean changes from day 1 showed an increase of 1.19 natural logarithm (ln) cell/mm3 in the corticosteroid group and an increase of 0.67 ln cell/mm3 in the placebo group (LS mean difference of the changes in ln (methylprednisolone minus placebo) 0.51, 95% CI (0.02 to 1.01), p = 0.043). A significant effect was also found for the interaction (p = 0.043) between corticosteroids and lymphopenia in CRP values at day 3, with lower values in patients without lymphopenia receiving corticosteroids after adjustments for potential confounders. Conclusion: In this exploratory post hoc analysis from ramdomized controlled trial (RCT) data, the response to corticosteroids, measured by CRP, may differ according to lymphocyte count. Further larger studies are needed to confirm this data. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Pneumonia)
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Open AccessArticle
Simultaneous Depression of Immunological Synapse and Endothelial Injury is Associated with Organ Dysfunction in Community-Acquired Pneumonia
J. Clin. Med. 2019, 8(9), 1404; https://doi.org/10.3390/jcm8091404 - 06 Sep 2019
Abstract
Rationale: A depressed expression of antigen presentation is, along with endothelial dysfunction, a recognized signature of severe community-acquired pneumonia (CAP). We aimed to evaluate the expression of a number of genes involved in the immunological synapse in non-critically ill CAP patients with or [...] Read more.
Rationale: A depressed expression of antigen presentation is, along with endothelial dysfunction, a recognized signature of severe community-acquired pneumonia (CAP). We aimed to evaluate the expression of a number of genes involved in the immunological synapse in non-critically ill CAP patients with or without organ dysfunction and to profile endothelial biomarkers such as proendothelin-1 (proET1) and proadrenomedullin (proADM). Methods: A nested study in a prospective cohort in CAP patients was performed. Expression levels of major histocompatibility complex class II DR alpha (HLA-DRA), CD40 ligand (CD40LG), CD3E, CD28, and inducible T-cell costimulator (ICOS) were quantified by using droplet digital polymerase chain reaction and endothelial biomarkers by immunofluorescence. Results: Ninety-four patients were included, 44.7% of whom had organ failure in one or more organs. A significant decrease in the expression of the five genes with increased levels of proadrenomedullin (proADM) and proendothelin-1 (proET1) was found in CAP with organ failure. The depressed expression of HLA-DRA (odds ratio (OR), 2.94), CD40LG (OR, 3.90), and CD28 (OR, 3.48) was independently associated with organ failure after adjustment for age, Charlson score, and severity. Conclusions. CAP with organ failure showed depressed expression of immunological synapse genes with increased levels of biomarkers denoting endothelial damage. Simultaneous profiling of immunological and endothelial signatures could help in the early identification of organ failure in CAP and in the implementation of personalized treatment. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Pneumonia)
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Open AccessArticle
Ventilator-Associated Pneumonia and PaO2/FIO2 Diagnostic Accuracy: Changing the Paradigm?
J. Clin. Med. 2019, 8(8), 1217; https://doi.org/10.3390/jcm8081217 - 14 Aug 2019
Abstract
Background: Ventilator-associated pneumonia (VAP) is associated to longer stay and poor outcomes. Lacking definitive diagnostic criteria, worsening gas exchange assessed by PaO2/FIO2 ≤ 240 in mmHg has been proposed as one of the diagnostic criteria for VAP. We [...] Read more.
Background: Ventilator-associated pneumonia (VAP) is associated to longer stay and poor outcomes. Lacking definitive diagnostic criteria, worsening gas exchange assessed by PaO2/FIO2 ≤ 240 in mmHg has been proposed as one of the diagnostic criteria for VAP. We aim to assess the adequacy of PaO2/FIO2 ≤ 240 to diagnose VAP. Methods: Prospective observational study in 255 consecutive patients with suspected VAP, clustered according to PaO2/FIO2 ≤ 240 vs. > 240 at pneumonia onset. The primary analysis was the association between PaO2/FIO2 ≤ 240 and quantitative microbiologic confirmation of pneumonia, the most reliable diagnostic gold-standard. Results: Mean PaO2/FIO2 at VAP onset was 195 ± 82; 171 (67%) cases had PaO2/FIO2 ≤ 240. Patients with PaO2/FIO2 ≤ 240 had a lower APACHE-II score at ICU admission; however, at pneumonia onset they had higher CPIS, SOFA score, acute respiratory distress syndrome criteria and incidence of shock, and less microbiological confirmation of pneumonia (117, 69% vs. 71, 85%, p = 0.008), compared to patients with PaO2/FIO2 > 240. In multivariate logistic regression, PaO2/FIO2 ≤ 240 was independently associated with less microbiological confirmation (adjusted odds-ratio 0.37, 95% confidence interval 0.15–0.89, p = 0.027). The association between PaO2/FIO2 and microbiological confirmation of VAP was poor, with an area under the ROC curve 0.645. Initial non-response to treatment and length of stay were similar between both groups, while hospital mortality was higher in patients with PaO2/FIO2 ≤ 240. Conclusion: Adding PaO2/FIO2 ratio ≤ 240 to the clinical and radiographic criteria does not help in the diagnosis of VAP. PaO2/FIO2 ratio > 240 does not exclude this infection. Using this threshold may underestimate the incidence of VAP. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Pneumonia)
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Open AccessArticle
Impact of Cefotaxime Non-susceptibility on the Clinical Outcomes of Bacteremic Pneumococcal Pneumonia
J. Clin. Med. 2019, 8(8), 1150; https://doi.org/10.3390/jcm8081150 - 01 Aug 2019
Abstract
Background: We aimed to analyze the impact of cefotaxime non-susceptibility on the 30-day mortality rate in patients receiving a third-generation cephalosporin for pneumococcal bacteremic pneumonia. Methods: We conducted a retrospective observational study of prospectively collected data from the Hospital Clinic of Barcelona. All [...] Read more.
Background: We aimed to analyze the impact of cefotaxime non-susceptibility on the 30-day mortality rate in patients receiving a third-generation cephalosporin for pneumococcal bacteremic pneumonia. Methods: We conducted a retrospective observational study of prospectively collected data from the Hospital Clinic of Barcelona. All adult patients with monomicrobial bacteremic pneumonia due to Streptococcus pneumoniae and treated with a third-generation cephalosporin from January 1991 to December 2016 were included. Risk factors associated with 30-day mortality were evaluated by univariate and multivariate analyses. Results: During the study period, 721 eligible episodes were identified, and data on the susceptibility to cefotaxime was obtainable for 690 episodes. Sixty six (10%) cases were due to a cefotaxime non-susceptible strain with a 30-day mortality rate of 8%. Variables associated with 30-day mortality were age, chronic liver disease, septic shock, and the McCabe score. Infection by a cefotaxime non-susceptible S. pneumoniae did not increase the mortality rate. Conclusion: Despite the prevalence of cefotaxime, non-susceptible S. pneumoniae has increased in recent years. We found no evidence to suggest that patients hospitalized with bacteremic pneumonia due to these strains had worse clinical outcomes than patients with susceptible strains. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Pneumonia)
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Open AccessArticle
Risk and Prognostic Factors in Very Old Patients with Sepsis Secondary to Community-Acquired Pneumonia
J. Clin. Med. 2019, 8(7), 961; https://doi.org/10.3390/jcm8070961 - 02 Jul 2019
Abstract
Background: Little is known about risk and prognostic factors in very old patients developing sepsis secondary to community-acquired pneumonia (CAP). Methods: We conducted a retrospective observational study of data prospectively collected at the Hospital Clinic of Barcelona over a 13-year period. [...] Read more.
Background: Little is known about risk and prognostic factors in very old patients developing sepsis secondary to community-acquired pneumonia (CAP). Methods: We conducted a retrospective observational study of data prospectively collected at the Hospital Clinic of Barcelona over a 13-year period. Consecutive patients hospitalized with CAP were included if they were very old (≥80 years) and divided into those with and without sepsis for comparison. Sepsis was diagnosed based on the Sepsis-3 criteria. The main clinical outcome was 30-day mortality. Results: Among the 4219 patients hospitalized with CAP during the study period, 1238 (29%) were very old. The prevalence of sepsis in this age group was 71%. Male sex, chronic renal disease, and diabetes mellitus were independent risk factors for sepsis, while antibiotic therapy before admission was independently associated with a lower risk of sepsis. Thirty-day and intensive care unit (ICU) mortality did not differ between patients with and without sepsis. In CAP-sepsis group, chronic renal disease and neurological disease were independent risk factors for 30-day mortality. Conclusion: In very old patients hospitalized with CAP, in-hospital and 1-year mortality rates were increased if they developed sepsis. Antibiotic therapy before hospital admission was associated with a lower risk of sepsis. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Pneumonia)
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Open AccessArticle
Lymphocytopenia as a Predictor of Mortality in Patients with ICU-Acquired Pneumonia
J. Clin. Med. 2019, 8(6), 843; https://doi.org/10.3390/jcm8060843 - 13 Jun 2019
Cited by 1
Abstract
Background: Intensive care unit-acquired pneumonia (ICU-AP) is a severe complication in patients admitted to the ICU. Lymphocytopenia is a marker of poor prognosis in patients with community-acquired pneumonia, but its impact on ICU-AP prognosis is unknown. We aimed to evaluate whether lymphocytopenia is [...] Read more.
Background: Intensive care unit-acquired pneumonia (ICU-AP) is a severe complication in patients admitted to the ICU. Lymphocytopenia is a marker of poor prognosis in patients with community-acquired pneumonia, but its impact on ICU-AP prognosis is unknown. We aimed to evaluate whether lymphocytopenia is an independent risk factor for mortality in non-immunocompromised patients with ICU-AP. Methods: Prospective observational cohort study of patients from six ICUs of an 800-bed tertiary teaching hospital (2005 to 2016). Results: Of the 473 patients included, 277 (59%) had ventilator-associated pneumonia (VAP). Receiver operating characteristic (ROC) analysis of the lymphocyte counts at diagnosis showed that 595 cells/mm3 was the best cut-off for discriminating two groups of patients at risk: lymphocytopenic group (lymphocyte count <595 cells/mm3, 141 patients (30%)) and non-lymphocytopenic group (lymphocyte count ≥595 cells/mm3, 332 patients (70%)). Patients with lymphocytopenia presented more comorbidities and a higher sequential organ failure assessment (SOFA) score at the moment of pneumonia diagnosis. Also, 28-day mortality and 90-day mortality were higher in patients with lymphocytopenia (28-day: 38 (27%) versus 59 (18%), 90-day: 74 (53%) versus 111 (34%)). In the multivariable model, <595 cells/mm3 resulted to be an independent predictor for 90-day mortality (Hazard Ratio 1.41; 95% Confidence Interval 1.02 to 1.94). Conclusion: Lymphocytopenia is an independent predictor of 90-day mortality in non-immunocompromised patients with ICU-AP. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Pneumonia)
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Open AccessArticle
Early Corticosteroid Therapy for Mycoplasma pneumoniae Pneumonia Irrespective of Used Antibiotics in Children
J. Clin. Med. 2019, 8(5), 726; https://doi.org/10.3390/jcm8050726 - 22 May 2019
Cited by 1
Abstract
Antibiotics’ effect on Mycoplasma pneumoniae (MP) infection still remains controversial. A prospective study of 257 children with MP pneumonia during a recent epidemic (2015–2016) was conducted. All MP pneumonia patients were treated with corticosteroids within 24–36 h after admission. Initially, oral prednisolone (1 [...] Read more.
Antibiotics’ effect on Mycoplasma pneumoniae (MP) infection still remains controversial. A prospective study of 257 children with MP pneumonia during a recent epidemic (2015–2016) was conducted. All MP pneumonia patients were treated with corticosteroids within 24–36 h after admission. Initially, oral prednisolone (1 mg/kg) or intravenous methylprednisolone (IVMP; 1–2 mg/kg) was administered for mild pneumonia patients, and IVMP (5–10 mg/kg/day) for severe pneumonia patients. If patients showed a persistent fever for 36–48 h or disease progression, additive IVMP (5 mg/kg or 10 mg/kg) was given. Thirty-three percent of patients received only a broad-spectrum antibiotic without a macrolide. The mean age and the male-to-female ratio was 5.6 ± 3.1 years and 1:1, respectively. Seventy-four percent of patients showed immediate defervescence within 24 h, and 96% of patients showed defervescence within 72 h with improvements in clinical symptoms. Three percent of patients (8/257) who received additive IVMP also showed clinical improvement within 48 h without adverse reactions. There were no clinical or laboratory differences between patients treated with a macrolide (n = 172) and without (n = 85). Early corticosteroid therapy might reduce disease morbidity and prevent disease progression in MP pneumonia patients without side effects, and antibiotics may have limited effects on MP infection. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Pneumonia)
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Open AccessArticle
Pleural Tap-Guided Antimicrobial Treatment for Pneumonia with Parapneumonic Effusion or Pleural Empyema in Children: A Single-Center Cohort Study
J. Clin. Med. 2019, 8(5), 698; https://doi.org/10.3390/jcm8050698 - 16 May 2019
Abstract
Parapneumonic effusion or pleural empyema (PPE/PE) is a frequent complication of community-acquired pneumonia (CAP) in children. Different management approaches exist for this condition. We evaluated a 14-day treatment with amoxicillin (AMX) with/without clavulanic acid (AMC) confirmed or modified by microbiological findings from pleural [...] Read more.
Parapneumonic effusion or pleural empyema (PPE/PE) is a frequent complication of community-acquired pneumonia (CAP) in children. Different management approaches exist for this condition. We evaluated a 14-day treatment with amoxicillin (AMX) with/without clavulanic acid (AMC) confirmed or modified by microbiological findings from pleural tap. Children ≤16 years of age with radiologically diagnosed PPE/PE and initial diagnostic pleural tap were included at University Children’s Hospital Zurich from 2001–2015. AMX/AMC was given for 14 days and rationalized according to microbiological pleural tap results. Clinical and radiological follow-up was scheduled until six months or full recovery. In 114 of 147 (78%) children with PPE/PE a pathogen was identified by culture, polymerase chain reaction (PCR), and/or antigen testing. Streptococcus pneumoniae was detected in 90 (79%), S. pyogenes in 13 (11%), and Staphylococcus aureus in seven cases (6%), all but two cultured pathogens (96%) were sensitive to AMX/AMC. One-hundred two of 147 (69%) patients received treatment with AMX/AMC for 14 days. They recovered more rapidly than patients with a different management (p = 0.026). Of 139 children with follow-up, 134 (96%) patients fully recovered. In conclusion, 14-day AMX/AMC treatment confirmed and rarely modified by microbiological findings from pleural tap resulted in full recovery in >95% of children with PPE/PE. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Pneumonia)
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Review

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Open AccessReview
Treatment Options for Colistin Resistant Klebsiella pneumoniae: Present and Future
J. Clin. Med. 2019, 8(7), 934; https://doi.org/10.3390/jcm8070934 - 28 Jun 2019
Cited by 2
Abstract
Multidrug-resistant (MDR) Klebsiella pneumoniae represents an increasing threat to human health, causing difficult-to-treat infections with a high mortality rate. Since colistin is one of the few treatment options for carbapenem-resistant K. pneumoniae infections, colistin resistance represents a challenge due to the limited [...] Read more.
Multidrug-resistant (MDR) Klebsiella pneumoniae represents an increasing threat to human health, causing difficult-to-treat infections with a high mortality rate. Since colistin is one of the few treatment options for carbapenem-resistant K. pneumoniae infections, colistin resistance represents a challenge due to the limited range of potentially available effective antimicrobials, including tigecycline, gentamicin, fosfomycin and ceftazidime/avibactam. Moreover, the choice of these antimicrobials depends on their pharmacokinetics/pharmacodynamics properties, the site of infection and the susceptibility profile of the isolated strain, and is sometimes hampered by side effects. This review describes the features of colistin resistance in K. pneumoniae and the characteristics of the currently available antimicrobials for colistin-resistant MDR K. pneumoniae, as well as the characteristics of novel antimicrobial options, such as the soon-to-be commercially available plazomicin and cefiderocol. Finally, we consider the future use of innovative therapeutic strategies in development, including bacteriophages therapy and monoclonal antibodies. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Pneumonia)
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