Pneumococcal serotypes in adults hospitalized with community-acquired pneumonia in Greece using urinary antigen detection tests: the EGNATIA study, November 2017 - April 2019.

Greece introduced a 13-valent pneumococcal conjugate vaccine (PCV13) into the infant national immunization program in 2010 (3 + 1 schedule until June 2019). Since 2015, PCV13 has been recommended for adults aged 19-64 years with comorbidities and adults ≥65 years sequentially with 23-valent pneumococcal polysaccharide vaccine (PPSV23). We examined pneumococcal serotype distribution among Greek adults aged ≥19 years hospitalized with community-acquired pneumonia (CAP) during November 2017-April 2019. This was an interim analysis of EGNATIA, a prospective study of adult hospitalized CAP in the cities of Ioannina and Kavala. Pneumococcus was identified using cultures, BinaxNow®, serotype-specific urinary antigen detection assays (UAD-1/2). Our analysis included overall 482 hospitalized CAP patients (mean age: 70.5 years; 56.4% male). 53.53% of patients belonged to the highest pneumonia severity index (PSI) classes (IV-V). Pneumococcus was detected in 65 (13.5%) patients, with more than half (57%) of cases detected only by UAD. Approximately two-thirds of pneumococcal CAP occurred in those aged ≥65 years (n = 40, 8.3% of CAP). More than half of pneumococcal CAP (n = 35, 53.8%) was caused by PCV13 serotypes. Most frequently detected PCV13 serotypes were 3, 19A, 23F, collectively accounting for 83% of PCV13 vaccine-type (VT) CAP and 6% of all-cause CAP. Overall, 82.9% of PCV13 VT CAP occurred among persons with an indication (age/risk-based) for PCV13 vaccination. Even with a mature PCV13 childhood immunization program, a persistent burden of PCV13 VT CAP exists in Greek adults. Strategies to increase PCV13 (and higher-valency PCVs, when licensed) coverage in adults should be implemented to reduce the disease burden.

An interim analysis of a prospective study in adults hospitalized with CAP in Greece.Serotype-specific urinary antigen detection assays were used to detect pneumococcus.A persistent burden of PCV13 vaccine-type CAP was observed in Greek adults.Improved PCV13 uptake and higher-valency PCVs may reduce the pneumococcal disease burden.

Outpatient Management of COVID-19 Disease: A Holistic Patient-Centered Proposal Based on the Greek Experience.

Novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic and affected more than 227 countries or territories, resulting in more than 179 million cases with over 3.890.00 deaths, as of June 25, 2021. The Hellenic Thoracic Society (HTS) during the second wave of COVID-19 pandemic released a guidance document for the management of patients with COVID-19 in the community and in hospital setting. In this review, with guidance the HTS document, we are discussing the outpatient management of COVID-19 patients, including the preventive measures, the patients' isolation and quarantine criteria of close contacts, the severity and risk stratification, including the decisions for advanced hospitalization, and the disease management at home in patients with mild disease and after hospital discharge for those with more severe disease.

Systemic Inflammatory Response and Outcomes in Community-Acquired Pneumonia Patients Categorized According to the Smoking Habit or Presence of Chronic Obstructive Pulmonary Disease.

The systemic inflammatory response (SIR) may help to predict clinical progression, treatment failure, and prognosis in community-acquired pneumonia (CAP). Exposure to tobacco smoke may affect the SIR; the role of smoking in CAP has not been consolidated. We evaluated the SIR and outcomes of hospitalized CAP patients stratified by smoking habits and the presence of COPD. This retrospective analysis was conducted at the Hospital Clinic of Barcelona. Baseline, clinical, microbiological, and laboratory variables were collected at admission, using C-reactive protein (CRP) levels as a marker of SIR. The study outcomes were pleural complications, hospital stay, non-invasive and invasive mechanical ventilation (IMV), and intensive care unit (ICU) admission. We also considered the in-hospital and 30-day mortality. Data were grouped by smoking habit (non-, former-, and current-smokers) and the presence of COPD. Current smokers were younger, had fewer comorbidities, and fewer previous pneumonia episodes. CRP levels were higher in current smokers than in other groups. Current smokers had a higher risk of pleural complications independent of CRP levels, the presence of pleuritic pain, and a higher platelet count. Current smokers more often required IMV and ICU admission. Current smokers have a greater inflammatory response and are at increased risk of pleural complications.

Community acquired pneumonia: a cost-of-illness analysis in Greece.

INTRODUCTION: Community acquired pneumonia (CAP) is an acute respiratory infection with high clinical and economic burden, especially when hospitalisation is required. The present study aimed to assess the mean direct cost per CAP outpatient and inpatient care in Greece, in the absence of previous estimates. METHODS: A retrospective analysis of patients at a tertiary hospital, treated between October 2015 and March 2016, was conducted. Resource use data for inpatients and outpatients were collected (diagnostic tests, medication, physician visits and length of hospitalisation, where applicable). Cost calculations followed a third party payer perspective. Additionally, two regression models were employed to identify the determinants of hospitalisation and the main drivers of inpatient and outpatient cost. RESULTS: Overall, 149 inpatients and 100 outpatients were included in the analysis. Mean hospitalisation duration was 11.35 days (standard deviation (SD)=9.71 days). Mean direct cost per patient was €110.64 (SD=€58.23) and €7406.56 (SD=€12,124.93) for outpatient and inpatient cases respectively. (At the time period for the study, €1.00 was approximately A$1.50.) The main inpatient cost driver was hospitalisation (94.97%), followed by medication (3.30%) and diagnostic tests (0.87%). For outpatients, key cost drivers, in order of magnitude, were prescribed medication (38.84%), diagnostic tests (33.51%) and physician visits (17.54%). The regression analyses showed that the probability of hospitalisation increases with age and number of symptoms, whereas average cost is mainly influenced by gender, duration and number of symptoms, and the presence of comorbidities. CONCLUSION: The results indicate that, in Greece, CAP is accompanied by a significant economic burden, mainly attributable to hospitalisation. Interventions toward reducing the influence of contributors to the incidence and probability of hospitalisation are essential from a clinical and policy perspective. Also, the association of symptoms - in terms of number and duration - and age with hospitalisation probability and costs highlights that special attention should be given to the high risk groups of the population, such as the elderly and the rural residents, both in terms of preventive and therapeutic services.

Emerging antibiotics for community-acquired pneumonia.

Introduction: Community-acquired pneumonia is the most common infection leading to hospitalization and death in all age groups, especially in elderly populations. Increasing antibiotic resistance among the common bacterial pathogens associated with community-acquired pneumonia, especially Streptococcus pneumoniae and staphylococci, has made its empirical treatment increasingly problematic, highlighting the need for effective antibiotic therapy.Areas covered: We searched PubMed and ClinicalTrials.gov for English-language reports of phase III clinical trials conducted between 2000 and 2019 concerning the antibiotic treatment of community-acquired pneumonia. We provide a summary of the latest approved drugs for this indication and highlight emerging drugs with a potential indication.Expert opinion: Ceftaroline (a new cephalosporine) and omadacycline (a cycline alternative), either parenterally or orally, are the only two new antibiotics to have been approved by the FDA for the treatment of community-acquired pneumonia in the last five years. Among the antimicrobials in development, Lefamulin (the first pleuromutilin), is currently in phase III development. Among the known antibiotic classes, solithromycin (a macrolide), nemonoxacin (a quinolone), and delafloxacin and zabofloxacin (both fluoroquinolones), have been studied in phase II and III in clinical trials. The availability of these new antibiotics may offer opportunities to improve the empirical treatment for community-acquired pneumonia.

Emerging strategies for the noninvasive diagnosis of nosocomial pneumonia.

Introduction: Hospital-acquired pneumonia is a common and therapeutically challenging diagnosis that can lead to severe sepsis, critical illness, and respiratory failure. In this review, we focus on efforts to enhance microbiological diagnosis of hospital-acquired pneumonia, including ventilator-associated pneumonia. Areas covered: A systematic literature review was conducted by searching Medline from inception to December 2018, including hand-searching of the reference lists for additional studies. The search strategy comprised the following common search terms: hospital pneumonia OR nosocomial pneumonia OR noninvasive OR molecular diagnostic tests (OR point-of-care systems OR VOC [i.e. volatile organic compounds]) OR rapid (or simple or quick test), including brand names for the most common commercial tests. Expert opinion: In recent years, the microbiological diagnosis of respiratory pathogens has improved significantly by the development and implementation of molecular diagnostic tests for pneumonia. Real-time polymerase chain reaction, hybridization, and mass spectrometry-based platforms dominate the scene, with microarray-based assays, multiplex polymerase chain reaction, and MALDI-TOF mass spectrometry capable of detecting the determinants of antimicrobial resistance (mainly ß-lactamase genes). Introducing these assays into routine clinical practice for rapid identification of the causative microbes and their resistance patterns could transform the care of pneumonia, improving antimicrobial selection, de-escalation, and stewardship.

Lymphocytopenia as a Predictor of Mortality in Patients with ICU-Acquired Pneumonia.

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.

Drugs that increase the risk of community-acquired pneumonia: a narrative review.

INTRODUCTION: Community-acquired pneumonia (CAP), a major cause of morbidity and mortality, is the leading infectious cause of death in the developed world. Population-based studies and systematic reviews have identified a large number of risk factors for the development of pneumonia in adults. In addition to age, lifestyle habits, and comorbidities, some forms of pharmacotherapy may also increase the risk for CAP. AREAS COVERED: MEDLINE, CENTRAL, and Web of Science were used in 2017 to search for case-control, cohort studies, as well as randomized controlled trials and meta-analysis that involved outpatient proton pump inhibitors (PPIs), inhaled corticosteroids (ICSs), antipsychotics, oral antidiabetics, and CAP diagnosis in patients aged >18 years. EXPERT OPINION: Our review confirmed that the use of ICSs, PPIs or antipsychotic drugs was independently associated with an increased risk for CAP. We also identified a positive association between specific oral antidiabetics and the development of pneumonia.

Twenty-year trend in mortality among hospitalized patients with pneumococcal community-acquired pneumonia.

BACKGROUND: There is only limited information on mortality over extended periods in hospitalized patients with pneumococcal community-acquired pneumonia (CAP). We aimed to evaluate the 30-day mortality and whether is changed over a 20-year period among immunocompetent adults hospitalized with pneumococcal CAP. METHODS: We conducted a retrospective observational study of data that were prospectively collected at the Hospital Clinic of Barcelona of all adult patients hospitalized with diagnosis of pneumococcal CAP over a 20-year period. To aid analysis, results were divided into four periods of 5 years each (1997-2001, 2002-2006, 2007-2011, 2012-2016). The primary outcome was 30-day mortality, but secondary outcomes included intensive care unit (ICU) admission, lengths of hospital and ICU-stays, ICU-mortality, and need of mechanical ventilation. RESULTS: From a cohort of 6,403 patients with CAP, we analyzed the data for 1,120 (17%) adults with a diagnosis of pneumococcal CAP. Over time, we observed decreases in the rates of alcohol consumption, smoking, influenza vaccination, and older patients (age ≥65 years), but increases in admissions to ICU and the need for non-invasive mechanical ventilation. The overall 30-day mortality rate was 8% (95% confidence interval, 6%-9%; 84 of 1,120 patients) and did not change significantly between periods (p = 0.33). Although, we observed a decrease in ICU-mortality comparing the first period (26%) to the second one (10%), statistical differences disappeared with adjustment (p0.38). CONCLUSION: Over time, 30-day mortality of hospitalized pneumococcal CAP did not change significantly. Nor did it change in the propensity-adjusted multivariable analysis. Since mortality in pneumococcal pneumonia has remained unaltered for many years despite the availability of antimicrobial agents with proven in vitro activity, other non-antibiotic strategies should be investigated.

Severe community-acquired pneumonia: Characteristics and prognostic factors in ventilated and non-ventilated patients.

BACKGROUND: Patients with severe community-acquired pneumonia (SCAP) and life-threatening acute respiratory failure may require invasive mechanical ventilation (IMV). Since use of IMV is often associated with significant morbidity and mortality, we assessed whether patients invasively ventilated would represent a target population for interventions aimed at reducing mortality of SCAP. METHODS: We prospectively recruited consecutive patients with SCAP for 12 years. We assessed the characteristics and outcomes of patients invasively ventilated at presentation of pneumonia, compared with those without IMV, and determined the influence of risks factors on mortality with a multivariate weighted logistic regression using a propensity score. RESULTS: Among 3,719 patients hospitalized with CAP, 664 (18%) had criteria for SCAP, and 154 (23%) received IMV at presentation of pneumonia; 198 (30%) presented with septic shock. In 370 (56%) cases SCAP was diagnosed based solely on the presence of 3 or more IDSA/ATS minor criteria. Streptococcus pneumoniae was the main pathogen in both groups. The 30-day mortality was higher in the IMV, compared to non-intubated patients (51, 33%, vs. 94, 18% respectively, p<0·001), and higher than that predicted by APACHE-II score (26%). IMV independently predicted 30-day mortality in multivariate analysis (adjusted odds-ratio 3·54, 95% confidence interval 1·45-8·37, p = 0·006). Other independent predictors of mortality were septic shock, worse hypoxemia and increased serum potassium. CONCLUSION: Invasive mechanical ventilation independently predicted 30-day mortality in patients with SCAP. Patients invasively ventilated should be considered a different population with higher mortality for future clinical trials on new interventions addressed to improve mortality of SCAP.

Investigational drugs in phase I and phase II clinical trials for the treatment of community-acquired pneumonia.

INTRODUCTION: Community acquired pneumonia is one of the main infections, remaining as a global cause of considerable morbidity and mortality. Successful treatment hinges on expedient delivery of appropriate antibiotic therapy tailored to both the likely pathogens and the severity of disease. Although antibiotic resistance is increasing and pharmaceutical companies continue to debate the profitability of introducing new antibacterial agents, an encouraging number of new molecules have recently been unveiled which target multidrug-resistant bacteria. Areas covered: Herein, the authors summarize the actual situation of novel antibiotics for CAP in phase I & II of development. For each set of compounds, the medical significance and possible clinical placement are discussed. Current treatment options from the most important international guidelines are also reviewed. Expert opinion: Our review shows that the new antibiotics in the pipeline belong to existing antibiotic classes as ß-lactams, macrolides, quinolones, oxazolidinones, tetracyclines, lipoglycopeptides, and cyclic lipopeptides and a few with a narrow spectrum of activity are novel compounds directed against novel targets. With rising outpatient antibiotic resistance in pneumonia, some of the compounds discussed are being considered for more rapid advancement in the pipeline, helping to increase the number of agents in later stages of development.

Telavancin in the treatment of Staphylococcus aureus hospital-acquired and ventilator-associated pneumonia: clinical evidence and experience.

Telavancin (TLV) is a lipoglycopeptide derivative of vancomycin (VAN), which has activity against Gram-positive aerobic bacteria, and is especially effective against methicillin-resistant Staphylococcus aureus (MRSA) and Gram-positive bacteria resistant to VAN. Comparative clinical studies of TLV have demonstrated noninferiority compared with VAN in the treatment of hospital-acquired Gram-positive pneumonia, with high cure rates for TLV-treated patients with monomicrobial S. aureus infection, including isolates with reduced VAN susceptibility. The results based on the patients' clinical response were supported by supplemental post-hoc analyses of 28-day mortality. In Europe and the USA, TLV is approved as a useful alternative for patients with difficult-to-treat, hospital-acquired MRSA pneumonia when there are very few alternatives. The present article reviews TLV's pharmacological characteristics and clinical efficacy resulting from clinical trials giving a detailed picture of its properties and position in the management of hospital-acquired pneumonia.

Emerging drugs for nosocomial pneumonia.

INTRODUCTION: Hospital-acquired pneumonia (HAP) is one of the leading nosocomial infections worldwide and is associated with an elevated morbidity and mortality and increased hospital costs. Nevertheless, prompt and adequate antimicrobial treatment is mandatory following VAP development, especially in the face of multidrug resistant pathogens. AREAS COVERED: We searched Pubmed and ClinicalTrials.gov site reports in English language of phase III clinical trials, between 2000-2016 referring to the antibiotic treatment of nosocomial pneumonia. We provide a summary of latest approved drugs for HAP and emerging drugs with potential indication nosocomial pneumonia. EXPERT OPINION: There are several promising compounds on their way, as tedizolid-a new oxazolidone, iclaprim-a novel drug, related to trimethoprim, plazomicin-a new aminoglycoside and two combinations of ceftazidime/avibactam and ceftolozane/tazobactam against MDR bacteria, especially against MRSA and Gram-negative ESBL bacteria.

Predictive and prognostic factors in patients with blood-culture-positive community-acquired pneumococcal pneumonia.

In patients with pneumococcal community-acquired pneumonia (CAP), the risk factors for bacteraemia and its impact on outcomes are not fully elucidated. We aimed to compare characteristics of patients with blood-culture-positive versus blood-culture-negative pneumococcal CAP, and to characterise bacteraemic serotypes.We describe a prospective, observational study on nonimmunocompromised patients with pneumococcal CAP, from 1996 to 2013. We define severe pneumonia according to American Thoracic Society/Infectious Diseases Society of America guidelines.Of a total of 917 patients with pneumococcal CAP, 362 had blood-culture-positive pneumococcal pneumonia (BCPPP; 39%). High C-reactive protein (CRP) (≥20 mg·dL(-1)) (odds ratio (OR) 2.36, 95% CI 1.45-3.85), pleural effusion (OR 2.03, 95% CI 1.13-3.65) and multilobar involvement (OR 1.69, 95% CI 1.02-2.79) were independently associated with bacteraemic CAP, while nursing home resident (OR 0.12, 95% CI 0.01-1.00) was found as a protective factor. Despite the clinical differences, BCPPP showed similar outcomes to blood-culture-negative pneumococcal pneumonia (BCNPP). 14% of the serotypes (period 2006-2013) causing bacteraemia are included in pneumococcal conjugate vaccine PVC7, 74% in pneumococcal conjugate vaccine PVC13 and 83% in pneumococcal polysaccharide vaccine PPSV23.Pleural effusion, a high level of CRP and multilobar involvement predicted an increased risk of BCPPP. Although BCPPP patients were more severely ill at admission, mortality was not significantly greater than in BCNPP patients.

Readmission for Acute Exacerbation within 30 Days of Discharge Is Associated with a Subsequent Progressive Increase in Mortality Risk in COPD Patients: A Long-Term Observational Study.

BACKGROUND AND OBJECTIVE: Twenty per cent of chronic obstructive pulmonary disease (COPD) patients are readmitted for acute exacerbation (AECOPD) within 30 days of discharge. The prognostic significance of early readmission is not fully understood. The objective of our study was to estimate the mortality risk associated with readmission for acute exacerbation within 30 days of discharge in COPD patients. METHODS: The cohort (n = 378) was divided into patients readmitted (n = 68) and not readmitted (n = 310) within 30 days of discharge. Clinical, laboratory, microbiological, and severity data were evaluated at admission and during hospital stay, and mortality data were recorded at four time points during follow-up: 30 days, 6 months, 1 year and 3 years. RESULTS: Patients readmitted within 30 days had poorer lung function, worse dyspnea perception and higher clinical severity. Two or more prior AECOPD (HR, 2.47; 95% CI, 1.51-4.05) was the only variable independently associated with 30-day readmission. The mortality risk during the follow-up period showed a progressive increase in patients readmitted within 30 days in comparison to patients not readmitted; moreover, 30-day readmission was an independent risk factor for mortality at 1 year (HR, 2.48; 95% CI, 1.10-5.59). In patients readmitted within 30 days, the estimated absolute increase in the mortality risk was 4% at 30 days (number needed to harm NNH, 25), 17% at 6-months (NNH, 6), 19% at 1-year (NNH, 6) and 24% at 3 years (NNH, 5). CONCLUSION: In conclusion a readmission for AECOPD within 30 days is associated with a progressive increased long-term risk of death.

The clinical management of lower respiratory tract infections.

The 2010 Global Burden of Disease Study reported that lower respiratory tract infections, including pneumonia, are the fourth most common cause of death globally. The etiology of acute bronchitis and asthma exacerbations is mostly viral and the therapy is symptomatic. Management decisions in community acquired pneumonia regarding site of care, extent of assessment, and level of treatment are based primarily on disease severity (outpatient, inpatient, ICU admission). Antibiotics are the main choice of treatment for patients with pneumonia, acute exacerbations (AE) of COPD (including increased sputum purulence and worsening shortness of breath) and AE of non-CF bronchiectasis. Inhaled antibiotics may represent a more optimal approach for the treatment and prevention of AE of non-CF bronchiectasis. Approved strategies for the prevention of exacerbations include smoking cessation and rehabilitation programs, drug therapy and vaccination.

Polymicrobial intensive care unit-acquired pneumonia: prevalence, microbiology and outcome.

BACKGROUND: Microbial aetiology of intensive care unit (ICU)-acquired pneumonia (ICUAP) determines antibiotic treatment and outcomes. The impact of polymicrobial ICUAP is not extensively known. We therefore investigated the characteristics and outcomes of polymicrobial aetiology of ICUAP. METHOD: Patients with ICUAP confirmed microbiologically were prospectively compared according to identification of 1 (monomicrobial) or more (polymicrobial) potentially-pathogenic microorganisms. Microbes usually considered as non-pathogenic were not considered for the etiologic diagnosis. We assessed clinical characteristics, microbiology, inflammatory biomarkers and outcome variables. RESULTS: Among 441 consecutive patients with ICUAP, 256 (58%) had microbiologic confirmation, and 41 (16%) of them polymicrobial pneumonia. Methicillin-sensitive Staphylococcus aureus, Haemophilus influenzae, and several Enterobacteriaceae were more frequent in polymicrobial pneumonia. Multi-drug and extensive-drug resistance was similarly frequent in both groups. Compared with monomicrobial, patients with polymicrobial pneumonia had less frequently chronic heart disease (6, 15% vs. 71, 33%, p = 0.019), and more frequently pleural effusion (18, 50%, vs. 54, 25%, p = 0.008), without any other significant difference. Appropriate empiric antimicrobial treatment was similarly frequent in the monomicrobial (185, 86%) and the polymicrobial group (39, 95%), as were the initial response to the empiric treatment, length of stay and mortality. Systemic inflammatory response was similar comparing monomicrobial with polymicrobial ICUAP. CONCLUSION: The aetiology of ICUAP confirmed microbiologically was polymicrobial in 16% cases. Pleural effusion and absence of chronic heart disease are associated with polymicrobial pneumonia. When empiric treatment is frequently appropriate, polymicrobial aetiology does not influence the outcome of ICUAP.

Ceftobiprole for the treatment of pneumonia: a European perspective.

Ceftobiprole, a new broad spectrum, parenteral cephalosporin, exhibits potent in vitro activity against a number of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae, and Gram-negative pathogens associated with hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP). Ceftobiprole has demonstrated noninferiority in two large-scale pivotal studies comparing it to ceftriaxone with or without linezolid in CAP, with clinical cure rates 86.6% versus 87.4%, or ceftazidime in HAP, with clinical cure rates of 77% versus 76%, respectively. However, ceftobiprole was inferior in the subgroup of patients undergoing mechanical ventilation. Ceftobiprole has so far demonstrated a good safety profile in preliminary studies, with similar tolerability to comparators. The most commonly observed adverse events of ceftobiprole included headache and gastrointestinal upset. It is the first cephalosporin monotherapy approved in the EU for the treatment of both CAP and HAP (excluding ventilator-associated pneumonia).