Pathogens In Community-acquired Pneumonia Research Articles

Antibiotic Resistance in Community-Acquired Pneumonia Pathogens.

The overwhelming majority of cases of community-acquired pneumonia (CAP) can be treated with the standard antibiotic regimens of a macrolide and cephalosporin or a fluoroquinolone. Despite high rates, current levels of β-lactam resistance generally do not result in treatment failure for patients with CAP when appropriate agents and doses are used. Following the introduction of the pneumococcal conjugate vaccines, the incidence of invasive pneumococcal disease declined drastically, coinciding with a decrease in penicillin resistance. Risk factors for methicillin-resistant S. aureus follow two patterns: (1) healthcare-associated risk factors and (2) pneumonia from exotoxin-producing community-acquired strains. The latter is associated with need for antibiotics which inhibit protein synthesis for optimal management. Since 2000, macrolide-resistance in M. pneumoniae has rapidly emerged worldwide, especially in Asian countries. The inability to routinely culture H. influenzae suggests that macrolide and β-lactam resistance, while present, is not a big issue. Unless risk factors for a hospital-associated strain are present, the most common Enterobacteriaceae to cause CAP, including Escherichia coli and Klebsiella, are generally susceptible to usual CAP antibiotics. Given the limited role of antibiotic resistance in CAP, a strong rationale is needed for use of antibiotics other than the standard β-lactam/macrolide or fluoroquinolone regimens.

Principles of Antibiotic Management of Community-Acquired Pneumonia.

Community-acquired pneumonia (CAP) encompasses a broad spectrum of disease severity and may require outpatient, inpatient, or intensive care management. Successful treatment hinges on expedient delivery of appropriate antibiotic therapy tailored to both the likely offending pathogens and the severity of disease. This review summarizes key principles in starting treatment and provides recommended empiric therapy regimens for each site of care. In addition, we discuss the antimicrobial and anti-inflammatory role macrolides play in CAP, as well as specific information for managing individual CAP pathogens such as community-acquired methicillin-resistant Staphylococcus aureus and drug-resistant Streptococcus pneumoniae. We also examine several novel antibiotics being developed for CAP and review the evidence guiding duration of therapy and current best practices for the transition of hospitalized patients from intravenous antibiotics to oral therapy.

Pharmacodynamic and pharmacokinetic profiling of delafloxacin in a murine lung model against community-acquired respiratory tract pathogens

Increasing antimicrobial resistance in community-acquired pneumonia (CAP) pathogens has contributed to infection-related morbidity and mortality. Delafloxacin is a novel fluoroquinolone with broad-spectrum activity against Gram-positive and -negative organisms, including Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to define the pharmacodynamic profile of delafloxacin against CAP pathogens using a neutropenic murine lung infection model. Five S. pneumoniae, 2 methicillin-susceptible S. aureus (MSSA), 2 MRSA and 2 Klebsiella pneumoniae isolates were studied. Delafloxacin doses varied from 0.5 mg/kg/day to 640 mg/kg/day and were given as once-daily to every 3 h regimens over the 24-h treatment period. Efficacy was measured as the change in log10 CFU at 24 h compared with 0-h controls. Plasma and bronchopulmonary pharmacokinetic studies were conducted. Delafloxacin demonstrated potent in vitro and in vivo activity. Delafloxacin demonstrated high penetration into the lung compartment, as epithelial lining fluid concentrations were substantially higher than free drug in plasma. The ratio of the area under the free drug concentration–time curve to the minimum inhibitory concentration of the infecting organism (fAUC/MIC) was the parameter that best correlated with the efficacy of the drug, and the magnitude required to achieve 1 log10 CFU reduction was 31.8, 24.7, 0.4 and 9.6 for S. pneumoniae, MRSA, MSSA and K. pneumoniae, respectively. The observed in vivo efficacy of delafloxacin was supported by the high pulmonary disposition of the compound. The results derived from this pre-clinical lung model support the continued investigation of delafloxacin for the treatment of community-acquired lower respiratory tract infections.

The imaging features of Mycoplasma pneumoniae pneumonia in children

Mycoplasma pneumoniae is a common pathogen of community acquired pneumonia in children.The imaging manifestations of Mycoplasma pneumoniae pneumonia in children varied, the understanding of the causes in clinical pediatrician is not sufficient.The common imaging appearances of chest X-ray, chest CT and chest magnetic resonance imaging (MRI) in children with Mycoplasma pneumoniae pneumonia attributed to age, course, clinical manifestations and severity of illness were summarized in this review. Key words: Mycoplasma pneumoniae; Chest X-ray; Chest CT

Granzyme A impairs host defense during Streptococcus pneumoniae pneumonia.

Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia (CAP). Granzyme A (GzmA) is a serine protease produced by a variety of cell types involved in the immune response. We sought to determine the role of GzmA on the host response during pneumococcal pneumonia. GzmA was measured in bronchoalveolar lavage fluid (BALF) harvested from CAP patients from the infected and contralateral uninfected side and in lung tissue slides from CAP patients and controls. In CAP patients, GzmA levels were increased in BALF obtained from the infected lung. Human lungs showed constitutive GzmA expression by both parenchymal and nonparenchymal cells. In an experimental setting, pneumonia was induced in wild-type (WT) and GzmA-deficient (GzmA(-/-)) mice by intranasal inoculation of S. pneumoniae In separate experiments, WT and GzmA(-/-) mice were treated with natural killer (NK) cell depleting antibodies. Upon infection with S. pneumoniae, GzmA(-/-) mice showed a better survival and lower bacterial counts in BALF and distant body sites compared with WT mice. Although NK cells showed strong GzmA expression, NK cell depletion did not influence bacterial loads in either WT or GzmA(-/-) mice. These results implicate that GzmA plays an unfavorable role in host defense during pneumococcal pneumonia by a mechanism that does not depend on NK cells.

Identification of pathogens by comprehensive real-time PCR versus conventional methods in community-acquired pneumonia in Japanese adults

Background: Community-acquired pneumonia (CAP) has high morbidity and mortality. Unfortunately, the pathogen detection rate using conventional culture methods is relatively low. We compared comprehensive real-time polymerase chain reaction (real-time PCR) analysis of nasopharyngeal swab specimens (NPS) and sputum samples against conventional methods for ability to detect causative pathogens of CAP.Methods: We prospectively enrolled adult CAP patients, including those with prior antibiotic use, from December 2012 to May 2014. For each patient, causative pathogens were investigated conventionally and by real-time PCR that can identify 6 bacterial and 11 viral pathogens.Results: Patients numbered 92 (mean age, 63 years; 59 male), including 30 (33%) with prior antibiotic use. Considering all patients, identification of causative pathogens by real-time PCR was significantly more frequent than by conventional methods in all patients (72% vs. 57%, p = 0.018). In patients with prior antibiotic use, identification rates also differed significantly (PCR, 77%; conventional, 50%; p = 0.027). Mixed infections were more frequent according to real-time PCR than conventional methods (26% vs. 4%, p < 0.001). By the real-time PCR, Streptococcus pneumoniae was most frequently identified (38%) as a causative pathogen, followed by Haemophilus influenzae (37%) and Mycoplasma pneumoniae (5%). PCR also identified viral pathogens (21%), with sensitivity enhanced by simultaneous examination of both NPS and sputum samples rather than only NPS samples.Conclusions: Real-time PCR of NPS and sputum samples could better identify bacterial and viral pathogens in CAP than conventional methods, both overall and in patients with prior antibiotic treatment.

Community-acquired pneumonia related to intracellular pathogens.

Community-acquired pneumonia (CAP) is associated with high rates of morbidity and mortality worldwide; the annual incidence of CAP among adults in Europe has ranged from 1.5 to 1.7 per 1000 population. Intracellular bacteria are common causes of CAP. However, there is considerable variation in the reported incidence between countries and change over time. The intracellular pathogens that are well established as causes of pneumonia are Legionella pneumophila, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Chlamydophila psittaci, and Coxiella burnetii. Since it is known that antibiotic treatment for severe CAP is empiric and includes coverage of typical and atypical pathogens, microbiological diagnosis bears an important relationship to prognosis of pneumonia. Factors such as adequacy of initial antibiotic or early de-escalation of therapy are important variables associated with outcomes, especially in severe cases. Intracellular pathogens sometimes appear to cause more severe disease with respiratory failure and multisystem dysfunction associated with fatal outcomes. The clinical relevance of intracellular pathogens in severe CAP has not been specifically investigated. We review the prevalence, general characteristics, and outcomes of severe CAP cases caused by intracellular pathogens.

Immune relevant issues on Mycoplasma pneumoniae infection

Mycoplasma pneumoniae(MP) is the smallest organism that dose not need a host cell for replication.It is one of the most common pathogens of community acquired pneumonia in children.In recent years, the incidence of pneumonia mycoplasma pneumonia increased year by year, and severe pneumonia mycoplasma pneumonia, refractory pneumonia mycoplasma pneumonia cases also increased.MP causes a variety of clinical presentations, in addition to respiratory infections, there are also many extrapulmonary manifestations.Immune response plays a very important part in pathogenesis of MP infection.This article focused on the immune aspects in pathogenesis and extends to some diagnosis and therapeutic implications. Key words: Mycoplasma pneumoniae; Immune; Pathogenesis

Clinical and epidemiological features of pneumonia in young men in a closed community

Streptococcus pneumoniae is the leading pathogen of community-acquired pneumonia (CAP) in adults. Therefore, vaccination is an important preventive measure against CAP. Methods. Clinical and epidemiological features of CAP were studied in young conscript soldiers (n = 114) aged 18 to 26 years who had been vaccinated using the 23-valent polysaccharide pneumococcal vaccine PPV23 (Sanofi Pasteur, France) in previous 30 days and in unvaccinated patients (n = 151). Clinical examination, laboratory blood tests, sputum microbiological examination, quantitative C-reactive protein (CRP) measurement, molecular examination of nasopharyngeal smears using polymerase chain reaction (PCR), chest X-ray and pulse oximetry were used. Pneumococcal antigen was determined in urine using immunochromatography (Binax NOW S. pneumoniae test, USA). Results. Established risk factors of CAP in men were low anthropometric parameters (weight, body mass index, chest circumference), chronic upper airway diseases, history of repeated pneumonias, and being unvaccinated against pneumococcus. In first 100 days of military conscript, the risk of CAP was 6.96 (95%CI: 3.39–14.58; p 0.05), Streptococcus spp. (19.0% vs 36.0%, respectively; р = 0.48), and S. pneumoniae (10.3% vs 4.1%, respectively; p > 0.05) according to sputum microbiological results. The urine pneumococcal antigen test was positive in 2.9% of vaccinated and in 1.4% of unvaccinated CAP patients. Conclusion. Vaccination with PPV23 could reduce the rate of pneumococcal CAP in high-risk patient groups.

Community-Acquired Pneumonia Due to Multidrug- and Non–Multidrug-Resistant Pseudomonas aeruginosa

Pseudomonas aeruginosa is not a frequent pathogen in community-acquired pneumonia (CAP). However, in patients with severe CAP, P aeruginosa can be the etiology in 1.8%to 8.3%of patients, with a case-fatality rate of 50%to 100%. We describe the prevalence, clinical characteristics, outcomes, and risk factors associated with CAP resulting from multidrug-resistant (MDR) and non-MDR P aeruginosa. Prospective observational study of 2,023 consecutive adult patients with CAP with definitive etiology. P aeruginosa was found in 77 (4%) of the 2,023 cases with microbial etiology. In 22 (32%) of the 68 cases of P aeruginosa with antibiogram data, the isolates were MDR. Inappropriate therapy was present in 49 (64%) cases of P aeruginosa CAP, including 17/22 (77%) cases of MDR P aeruginosa CAP. Male sex, chronic respiratory disease, C-reactive protein<12.35mg/dL, and pneumonia severity index risk class IV to V were independently associated with P aeruginosa CAP. Prior antibiotic treatment was more frequent in MDR P aeruginosa CAP compared with non-MDR P aeruginosa (58%vs29%, P= .029), and was the only risk factor associated with CAP resulting from MDR P aeruginosa. In the multivariate analysis, age≥65 years, CAP resulting from Paeruginosa, chronic liver disease, neurologic disease, nursing home, criteria of ARDS, acute renal failure, ICU admission, and inappropriate empiric treatment were the factors associated with 30-day mortality. P aeruginosa is an individual risk factor associated with mortality in CAP. The risk factors described can help clinicians to suspect P aeruginosa and MDR P aeruginosa.

Community-acquired Haemophilus influenzae pneumonia--New insights from the CAPNETZ study.

We aimed to identify clinical characteristics and to assess effectiveness of different initial antibiotic regimens in adult patients with community-acquired pneumonia (CAP) caused by Haemophilus influenzae. Characteristics were compared between patients with H. influenzae monoinfection versus CAP of other and unknown aetiology enrolled by the German prospective cohort study CAPNETZ. Impact of initial antibiotic treatment on "early clinical response" according to FDA criteria and overall clinical cure were analysed. H. influenzae was found in 176 out of 2790 patients with pathogen detection (6.3%). Characteristics significantly associated with a H. influenzae CAP (p<0.017) included purulent sputum, prior pneumococcal vaccination and respiratory co-morbidities. Early clinical response rates on day 4 did not differ between patients receiving any mono- versus combination therapy (85.9% versus 88%), but were numerically higher for regimens including any fluoroquinolone (96.7%) and lower under macrolide monotherapy (70%). Initial CURB-65 score and chronic liver disease were identified as negative predictors for "early clinical response". At day 14, overall clinical cure was 91.9%. H. influenzae was a common CAP pathogen, particularly in patients with previous pneumococcal vaccination and respiratory co-morbidities. Severity of illness and chronic liver disease were associated with a lower rate of "early clinical response".

Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia.

The frequent lack of a microbiological diagnosis in community-acquired pneumonia (CAP) impairs pathogen-directed antimicrobial therapy. This study assessed the use of comprehensive multibacterial, multiviral molecular testing, including quantification, in adults hospitalized with CAP. Clinical and laboratory data were collected for 323 adults with radiologically-confirmed CAP admitted to 2 UK tertiary care hospitals. Sputum (96%) or endotracheal aspirate (4%) specimens were cultured as per routine practice and also tested with fast multiplex real-time polymerase-chain reaction (PCR) assays for 26 respiratory bacteria and viruses. Bacterial loads were also calculated for 8 bacterial pathogens. Appropriate pathogen-directed therapy was retrospectively assessed using national guidelines adapted for local antimicrobial susceptibility patterns. Comprehensive molecular testing of single lower respiratory tract (LRT) specimens achieved pathogen detection in 87% of CAP patients compared with 39% with culture-based methods. Haemophilus influenzae and Streptococcus pneumoniae were the main agents detected, along with a wide variety of typical and atypical pathogens. Viruses were present in 30% of cases; 82% of these were codetections with bacteria. Most (85%) patients had received antimicrobials in the 72 hours before admission. Of these, 78% had a bacterial pathogen detected by PCR but only 32% were culture-positive (P < .0001). Molecular testing had the potential to enable de-escalation in number and/or spectrum of antimicrobials in 77% of patients. Comprehensive molecular testing significantly improves pathogen detection in CAP, particularly in antimicrobial-exposed patients, and requires only a single LRT specimen. It also has the potential to enable early de-escalation from broad-spectrum empirical antimicrobials to pathogen-directed therapy.

Dectin-2-dependent host defense in mice infected with serotype 3 Streptococcus pneumoniae.

BackgroundStreptococcus pneumoniae, a major causative bacterial pathogen of community-acquired pneumonia, possesses a thick polysaccharide capsule. Host defense against this bacterium is mediated by activation of innate immune cells that sense bacterial components. Recently, C-type lectin receptors (CLRs) have garnered much attention in elucidating the recognition mechanism of pathogen-derived polysaccharides.MethodsIn the present study, we first compared the clinical course and neutrophil accumulation in the lungs of Dectin-2 knock-out (KO) and wild type (WT) mice. Mice were infected intratracheally with a serotype 3 strain of S. pneumoniae, and S. pneumoniae bacterial engulfment by neutrophils and inflammatory cytokine and anti-pneumococcal polysaccharide-specific IgG levels were evaluated in bronchoalveolar lavage fluid (BALF). We also examined the effect of Dectin-2 deficiency on interleukin (IL)-12 production by bone marrow-derived dendritic cells (BM-DCs) stimulated with the bacterial components.ResultsS. pneumonia-infected Dectin-2KO mice had a shorter survival time, larger bacterial burden and lower interferon gamma (IFN-γ) production in the lungs than WT mice. Although neutrophilic infiltration in the lungs was equivalent between Dectin-2KO mice and WT mice, S. pneumonia engulfment by neutrophils was attenuated in Dectin-2KO mice compared to WT mice. The anti-pneumococcal polysaccharide-specific IgG and IgG3 levels in BALF were lower in Dectin-2KO mice than in WT mice. When BM-DCs were stimulated with S. pneumoniae culture supernatant or its Concanavalin A (ConA)-bound fraction, IL-12 production was abrogated in Dectin-2KO mice compared to WT mice.ConclusionsWe demonstrated that Dectin-2 is intimately involved in the host defense against infection with a serotype 3 strain of S. pneumoniae. Dectin-2-dependent IL-12 production may contribute to IFN-γ synthesis and subsequent production of serotype-specific anti-capsular polysaccharide IgG after S. pneumoniae infection, which may promote S. pneumoniae bacterial opsonization for engulfment.

Atypical pathogen infection in community-acquired pneumonia.

Community-acquired pneumonia (CAP) is a world wide cause of morbidity and mortality. The etiology of CAP is different between countries and changes over time. With the increasing incidence, atypical pathogens are attracting more and more attention all over the world. In many countries, atypical pathogens are one of the main pathogens of CAP, and even could be the most prevalent etiology in China. Atypical pathogen infections can cause multi-system complications, which leads to a worse prognosis. Although still controversial, empirical antibiotic coverage of atypical pathogens in CAP may improve outcomes, shorten length of hospitalization, reduce mortality and lower total hospitalization costs. The macrolide resistance rate of atypical pathogens, especially Mycoplasma Pneumoniae (M. Pneumoniae) is high, so fluoroquinolones or tetracyclines should be considered as alternative therapy.

Role of Nucleotide-Binding Oligomerization Domain-Containing (NOD) 2 in Host Defense during Pneumococcal Pneumonia.

Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD) 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2 -/-) and wild-type (Wt) alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2 -/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39), an isogenic capsule locus deletion mutant (D39Δcps) or serotype 3 S. pneumoniae (6303) via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2 -/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2 -/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2 -/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2 -/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δcps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2.

Development and characterization of a novel model of invasive pneumococcal pneumonia in invasively ventilated PIGS

Streptococcus pneumoniae is the most common causative pathogen of community-acquired pneumonia (CAP). Often, patients with pneumococcal CAP are admitted into intensive care units, particularly when affected by invasive serotypes.

The clinical impact of the detection of potential etiologic pathogens of community-acquired pneumonia

The etiology of community-acquired pneumonia (CAP) is determined in less than half of the patients based on cultures of sputum and blood plus testing urine for the antigens of Streptococcus pneumoniae and Legionella pneumophila. This study added nasal polymerase chain reaction (PCR) probes for S. pneumoniae, Staphylococcus aureus, and respiratory viruses. Serum procalcitonin (PCT) levels were measured. Pathogens were identified in 78% of the patients. For detection of viruses, patients were randomized to either a 5-virus laboratory-generated PCR bundle or the 17-virus FilmArray PCR platform. The FilmArray PCR platform detected more viruses than the laboratory-generated bundle and did so in less than 2hours. There were fewer days of antibiotic therapy, P=0.003, in CAP patients with viral infections and a low serum PCT levels.

Community-Acquired Pneumonia: Pathogenesis of Acute Cardiac Events and Potential Adjunctive Therapies

Despite advances in antimicrobial chemotherapy and access to sophisticated intensive care facilities, bacterial community-acquired pneumonia (CAP) continues to carry an unacceptably high mortality rate of 10% to 15% in hospitalized cases. CAP, considered by many to be the most underestimated disease worldwide, poses a particular threat to the elderly whose numbers are steadily increasing in developed countries. Indeed, elderly patients with severe CAP, as well as those with other risk factors, are at significant risk for development of inflammation-mediated acute cardiac events that may undermine the success of antimicrobial therapy. Adjunctive antiinflammatory strategies are, therefore, of considerable potential benefit in this setting. Currently, the most promising of these are the macrolides, corticosteroids, and, more recently, statins, all of which target immune/inflammatory cells. In addition, recent insights into the immunopathogenesis of acute coronary events in patients with CAP have revealed a probable pivotal role of platelet activation, potentially modifiable by agents that possess antiinflammatory or platelet-targeted activities or both. Statins, which not only possess antiinflammatory activity but also appear to target several pathways involved in platelet activation, seem particularly well suited as adjuncts to antibiotic therapy in bacterial CAP. Following a brief consideration of the immunopathogenesis of bacterial CAP, this review is focused on mechanisms of platelet activation by CAP pathogens, as well as the pharmacologic control thereof, with emphasis on statins.

Epidemiology and clinical profiles of Mycoplasma pneumoniae infection in hospitalized infants younger than one year

Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen of community-acquired pneumonia in children, but the epidemiology and clinical features of M. pneumoniae infection in infants are reported in only a few studies. This study aims to evaluate possible age-related differences in the presenting clinical features in infants with M.pneumoniae infection. 24-month longitudinal study on lower respiratory tract infection (LRTI) caused by M.pneumoniae, confirmed by both serology and polymerase chain reaction, was performed. Medical records of patients were reviewed for demographic, clinical and microbiological characteristics. Out of 2174 infants with LRTI admitted to the Children's Hospital Affiliated to Soochow University in Jiangsu Province, 80 were diagnosed with M. pneumoniae infection. We found that 15 were aged 1 to <5 months; 29 were aged 5 to <9 months; and 36 were aged 9 to <12 months. M. pneumoniae infection mainly occurred in August to October. The presence of fever with a maximum temperature of >39.0°C for ≥3 days was more common in the 9 to <12 month age group (P<0.05). Laboratory tests showed that the infants aged 9-12 months had a higher peripheral leukocyte (P=0.035) and neutrophil (P=0.015) count and a higher CRP level (P=0.041). Moreover, the median length of hospitalization for infants aged 1 to <5 months was shorter than that in the other two groups. Our work provides important clinical information about infants with M. pneumoniae infection and highlights that younger infants with M. pneumoniae infection may have a milder clinical course than older infants.

Thrombocytopenia impairs host defense during murine Streptococcus pneumoniae pneumonia.

Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia. In patients, thrombocytopenia is correlated with an adverse outcome of pneumonia. Platelets can modulate the host response to infection in several ways, that is, by facilitating clot formation, production of antimicrobial proteins, and interaction with neutrophils. We studied the effect of thrombocytopenia during murine pneumococcal pneumonia. Animal study. University research laboratory. Mice. Pneumonia was induced by intranasal inoculation of S. pneumoniae. Platelets were depleted by anti-mouse thrombocyte serum; controls received nonimmunogenic serum. In separate studies, mice were treated with the platelet P2Y12 receptor inhibitor clopidogrel or placebo. Thrombocytopenic mice (platelet counts < 1% of uninfected controls) showed a reduced survival during pneumococcal pneumonia (27% vs 75% among controls; p = 0.003), which was associated with higher bacterial loads in lungs, spleen, and blood. Thrombocytopenic mice showed enhanced coagulation activation (thrombin-antithrombin complexes) in plasma. Proinflammatory cytokine levels were higher in plasma but not in lungs of thrombocytopenic mice. Although clopidogrel treatment strongly prolonged the bleeding time, it did not impact on bacterial loads during pneumococcal pneumonia. Platelets play a protective role during pneumococcal pneumonia independent of their aggregation.