Sputum Gram Research Articles

Drug Treatment of Pneumococcal Pneumonia in the Elderly

Streptococcus pneumoniae has been recognised as a major cause of pneumonia since the time of Sir William Osler. Drug-resistant S. pneumoniae (DRSP), which have gradually become resistant to penicillins as well as more recently developed macrolides and fluoroquinolones, have emerged as a consequence of indiscriminate use of antibacterials coupled with the ability of the pneumococcus to adapt to a changing antibacterial milieu. Pneumococci use cell wall choline components to bind platelet-activating factor receptors, colonise mucosal surfaces and evade innate immune defenses. Numerous virulence factors that include hyaluronidase, neuraminidase, iron-binding proteins, pneumolysin and autolysin then facilitate cytolysis of host cells and allow tissue invasion and bloodstream dissemination. Changes in pneumococcal cell wall penicillin-binding proteins account for resistance to penicillins, mutations in the ermB gene cause high-level macrolide resistance and mutations in topoisomerase IV genes coupled with GyrA gene mutations alter DNA gyrase and lead to high-level fluoroquinolone resistance. Risk factors for lower respiratory tract infections in the elderly include age-associated changes in oral clearance, mucociliary clearance and immune function. Other risks for developing pneumonia include poor nutrition, hypoalbuminaemia, bedridden status, aspiration, recent viral infection, the presence of chronic organ dysfunction syndromes including parenchymal lung disease and recent antibacterial therapy. Although the incidence of infections caused by DRSP is rising, the effect of an increase in the prevalence of resistant pneumococci on mortality is not clear. When respiratory infections occur, rapid diagnosis and prompt, empirical administration of appropriate antibacterial therapy that ensures adequate coverage of DRSP is likely to increase the probability of a successful outcome when treating community-acquired pneumonia in elderly patients, particularly those with multiple risk factors for DRSP. A chest x-ray is recommended for all patients, but other testing such as obtaining a sputum Gram's smear is not necessary and should not prolong the time gap between clinical suspicion of pneumonia and antibacterial administration. The selection of antibacterials should be based upon local resistance patterns of suspected organisms and the bactericidal efficacy of the chosen drugs. If time-dependent agents are chosen and DRSP are possible pathogens, dosing should keep drug concentrations above the minimal inhibitory concentration that is effective for DRSP. Treatment guidelines and recent studies suggest that combination therapy with a beta-lactam and macrolide may be associated with a better outcome in hospitalised patients, and overuse of fluoroquinolones as a single agent may promote quinolone resistance. The ketolides represent a new class of macrolide-like antibacterials that are highly effective in vitro against macrolide- and azalide-resistant pneumococci. Pneumococcal vaccination with the currently available polysaccharide vaccine is thought to confer some preventive benefit (preventing invasive pneumococcal disease), but more effective vaccines, such as nonconjugate protein vaccines, need to be developed that provide broad protection against pneumococcal infection.

Routine Sputum Culture of Questionable Value in Community-Acquired Pneumonia

Recent study findings and professional guidelines have challenged the practice of using sputum Gram stain and culture to make decisions about antibiotic use for community-acquired pneumonia (CAP). To assess the value of sputum collection relative to CAP severity, researchers in Spain studied 1669 consecutive patients with evidence …

Give Gram Stain and Culture Another Chance

Sputum Gram stain and culture were once the gold standard of diagnosis in patients with pneumonia but have been discounted in recent years, with published sensitivity estimates ranging as low as 20% for both techniques. How often are external factors to blame for their poor performance? Researchers …

Community-Acquired Pneumonia in Southeast Asia: The Microbial Differences Between Ambulatory and Hospitalized Patients

To determine microbial agents causing community-acquired pneumonia (CAP) in Southeast Asia. A prospective study. Three general hospitals in Thailand. Two hundred forty-five adult patients fulfilling the clinical criteria of CAP from September 1998 to April 2001. Investigations included sputum Gram stain and culture, blood culture, pleural fluid culture (if presented), urine antigen for Legionella pneumophila and Streptococcus pneumoniae, and serology for Mycoplasma pneumoniae, Chlamydia pneumoniae, and L pneumophila. There were 98 outpatients and 147 hospitalized patients included in the study, and an organism was identified in 74 of 98 outpatients (75.5%) and 105 of 147 of the hospitalized patients (71.4%). C pneumoniae (36.7%), M pneumoniae (29.6%), and S pneumoniae (13.3%) were the most frequent causative pathogens found in outpatients, while S pneumoniae (22.4%) and C pneumoniae (16.3%) were the most common in hospitalized patients. There was a significantly higher incidence of C pneumoniae (36.7% vs 16.3%, respectively; p < 0.001) and M pneumoniae (29.6% vs 6.8%; p < 0.001, respectively) in the outpatients than in the hospitalized patients. The incidence of S pneumoniae, L pneumophila, and mixed infections was not different between the groups. Mixed infections were presented in 13 of 98 outpatients (13.3%) and 9 of 147 hospitalized patients (6.1%), with C pneumoniae being the most frequent coinfecting pathogen. The data indicate that the core organisms causing CAP in Southeast Asia are not different from those in the Western countries. The guidelines for the treatment of patients with CAP, therefore, should be the same.

Classical and latent class analysis evaluation of sputum polymerase chain reaction and urine antigen testing for diagnosis of pneumococcal pneumonia in adults.

Diagnosis of pneumococcal pneumonia is complicated by the lack of a diagnostic reference standard that is highly sensitive and specific. Latent class analysis (LCA) is a mathematical technique that relates an unobserved ("latent") infection to multiple diagnostic test results by use of a statistical model. We used classical analysis and LCA to evaluate the sensitivity and specificity of blood culture, sputum Gram stain, sputum polymerase chain reaction (PCR), and urine antigen testing for diagnosing pneumococcal pneumonia among 149 adults with community-acquired pneumonia. On the basis of LCA models, sensitivity of autolysin PCR and pneumolysin PCR was 82% and 89%, respectively, but specificity was low, 38% and 27%, respectively. For urine antigen testing, sensitivity was 77%-78%, and specificity was 67%-71%. Results of the LCA models were comparable with those obtained from classical analysis. LCA may be useful for diagnostic test evaluation and for determining the prevalence of pneumococcal infection in epidemiological studies of community-acquired pneumonia and in vaccine efficacy trials.

Rapid diagnostic testing for the identification of respiratory agents in the emergency department

Pneumonia, influenza, and respiratory syncytial virus (RSV) are common causes of illness in children presenting to an emergency department or clinie. Rapid tests to aid in their diagnosis are available. Sputum gram stain can be helpful in selected patients with pneumonia. Assays based on enzyme immunoassay are available for influenza and RSV and are quite sensitive. However, there are problems with using these assays on a routine basis in the outpatient setting. Physicians should be aware of how the frequency of a disease affects the predictive value of a diagnostic assay. If specific therapy for the infection is not available or is not indicated, a specific diagnosis is generally not required. Routine testing for influenza and RSV may be helpful in inpatients and in selected high-risk outpatients, but is otherwise of limited value.

The Role Of a Typical Pathogens in Nursing Home Pneumonia

The empiric coverage of atypical pathogens (Legionella, Chlamydia pneumoniae, and Mycoplasma pneumoniae) in nursing home pneumonia is a controversial area. Relatively recent reviews of nursing home pneumonia do not include recommendations for such empiric coverage. This includes recommendations from the Long-Term Care Committee of the Society for Healthcare Epidemiology in America (SHEA) published in 2000. 1 Nicolle LE Bentley DW Garibaldi R SHEA Long-Term-Care Committee et al. Antimicrobial use in long-term care facilities. Infect Control Hosp Epidemiol. 2000; 21: 537-545 Crossref PubMed Scopus (211) Google Scholar , 2 Muder RR Pneumonia in residents of long-term care facilities: Epidemiology, etiology, management and prevention. Am J Med. 1998; 105: 319-330 Abstract Full Text Full Text PDF PubMed Scopus (266) Google Scholar , 3 Medina-Walpole AM Katz PR Nursing home-acquired pneumonia. J Am Geriatr Soc. 1999; 47: 1005-1015 Crossref PubMed Scopus (76) Google Scholar Data on the role of atypical pathogens in nursing homes is limited. Coverage of “atypicals” is not proven to be necessary and could contribute to the emergence of resistant pathogens. The Infectious Disease Society of America (IDSA) however, recommends that without a quality gram stain and/or laboratory evidence of a “strongly suspected” specific pathogen that empiric coverage of community-acquired pneumonia include atypical pathogens. 4 Bartlett JG Dowell SF Mandell LA et al. Practice Guidelines for the management of community-acquired pneumonia in adults. Clin Infect Dis. 2000; 31: 347-382 Crossref PubMed Scopus (1433) Google Scholar Current American Thoracic Society (ATS) guidelines for community-acquired pneumonia state that, “A sputum gram stain cannot be used to focus initial empiric antibiotic therapy (contrary to ISDA), but could be used to broaden initial therapy.” Committee members were concerned about co-infections with bacteria and atypical pathogens. Gram stain and culture was recommended if a resistant organism not covered by empiric treatment was suspected. Resistant organisms such as methicillin resistant Staphylococcus aureus (MRSA) are endemic in many nursing homes. Recommended empiric coverage includes atypical pathogens. 5 Official statement of the American Thoracic Society. Guidelines for the management of adults with community-acquired pneumonia: Diagnosis, assessment of severity, antimicrobial therapy and prevention. Am J Resp Crit Care Med. 2001; 163: 1730 Crossref PubMed Scopus (2022) Google Scholar The Canadian guidelines recommend obtaining a quality sputum specimen in hospitalized patients stating, “Once an etiologic agent has been appropriately identified, the in vitro susceptibility of the pathogen has been confirmed, and infection with a co-pathogen has been excluded, initial empirical therapy should be modified so that treatment is directed at the specific pathogen(s) involved.” 6 Mandell LA Marrie TJ Grossman RF the Canadian Community-Acquired Pneumonia Working Group et al. Canadian guidelines for the initial management of community-acquired pneumonia: An evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society. Clin Infect Dis. 2000; 31: 383-421 Crossref PubMed Scopus (623) Google Scholar However, exclusion of a co-pathogen (ie, an atypical) is seldom accomplished. Recommended empiric coverage includes the atypical pathogens. 6 Mandell LA Marrie TJ Grossman RF the Canadian Community-Acquired Pneumonia Working Group et al. Canadian guidelines for the initial management of community-acquired pneumonia: An evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society. Clin Infect Dis. 2000; 31: 383-421 Crossref PubMed Scopus (623) Google Scholar

Prevención y tratamiento de la neumonía adquirida en la comunidad en pacientes adultos: Un enfoque para la atención primaria

Community-acquired pneumonia is a frequent cause of morbidity, hospitalization and death especially among patients with risk factors. Several agents can provoke this condition and their relevance change according to specific epidemiological exposures, time of the year and comorbidity, being Streptococcus pneumoniae the most frequent etiological agent followed by Mycoplasma pneumoniae, Chlamydia pneumoniae, respiratory viruses and Haemophilus influenzae. Management requires proper identification of the most vulnerable patients and prompt admittance and X-ray confirmation to analyze extension, complications or differential diagnosis. Etiological studies are limited by the low sensitivity and specificity of the sputum Gram stain, the invasive nature of some techniques or the high cost of a comprehensive study. Nonetheless, etiological studies are relevant on severe cases, immunosuppressed patients or those without response to an empirical treatment. New diagnostic tests include serological studies for atypical pathogens, direct detection of viral agents or pneumococcal antigens on sputum samples and Legionella pneumophila serotype 1 antigen detection in urine. Penicillin resistant pneumococcal (PRP) isolates associated to pneumonia or bacteremia as well as isolates with resistance to third generation cefalasporins or macrolides are still infrequently observed among adult patients in Chile. Notwithstanding, worldwide experience indicates that patients affected by PRP isolates and treated with penicillin do not evolve with a higher risk for treatment failure, except for those cases where the MIC for penicillin is equal or higher than 4 µg/mL

Community-Acquired Pneumonia

We initiated a prospective study with a group of practitioners to assess the etiology, clinical presentation, and outcome of community-acquired pneumonia in patients diagnosed in the outpatient setting. All patients with signs and symptoms suggestive of pneumonia and an infiltrate on chest X-ray underwent an extensive standard workup and were followed over 4 weeks. Over a 4-year period, 184 patients were eligible, of whom 170 (age range, 15-96 yr; median, 43 yr) were included and analyzed. In 78 (46%), no etiologic agent could be demonstrated. In the remaining 92 patients, 107 etiologic agents were implicated: 43 were due to "pyogenic" bacteria (39 Streptococcus pneumoniae, 3 Haemophilus spp., 1 Streptococcus spp.), 39 were due to "atypical" bacteria (24 Mycoplasma pneumoniae, 9 Chlamydia pneumoniae, 4 Coxiella burnetii, 2 Legionella spp.), and 25 were due to viruses (20 influenza viruses and 5 other respiratory viruses). There were only a few statistically significant clinical differences between the different etiologic categories (higher age and comorbidities in viral or in episodes of undetermined etiology, higher neutrophil counts in "pyogenic" episodes, more frequent bilateral and interstitial infiltrates in viral episodes). There were 2 deaths, both in patients with advanced age (83 and 86 years old), and several comorbidities. Only 14 patients (8.2%) required hospitalization. In 6 patients (3.4%), the pneumonia episode uncovered a local neoplasia. This study shows that most cases of community-acquired pneumonia have a favorable outcome and can be successfully managed in an outpatient setting. Moreover, in the absence of rapid and reliable clinical or laboratory tests to establish a definite etiologic diagnosis at presentation, the spectrum of the etiologic agents suggest that initial antibiotic therapy should cover both S. pneumoniae and atypical bacteria, as well as possible influenza viruses during the epidemic season.

Community-Acquired Pneumonia

Community-Acquired Pneumonia

Nonvalue of the Initial Microbiological Studies in the Management of Nonsevere Community-Acquired Pneumonia

To assess the value of the initial microbiological studies (MBS), consisting of sputum Gram's stains, sputum cultures, and blood cultures, in the etiologic diagnosis of community-acquired pneumonia (CAP) without comorbidity. A prospective study of 74 adult patients hospitalized with nonsevere CAP empirically treated according to the American Thoracic Society guidelines (ATS-GL) and evaluated with Gram's stains and cultures of valid sputum specimens and blood cultures. University-affiliated community hospital. Gram's stain of a valid sputum specimen failed to identify the etiologic agent in all patients. Sputum cultures identified pathogens in only four patients (5%). The results of all blood cultures were negative. All patients responded to the initial empiric antibiotic coverage selected according to the ATS-GL, and the results of the initial MBS had no clinical impact. The initial MBS, such as sputum Gram's stains, sputum cultures, and blood cultures, have no value in the management of nonsevere CAP without comorbid factors.

Community-Acquired Pneumonia

Community-Acquired Pneumonia

Sputum Gram Stains Still Sometimes Worthwhile

Studies differ on the usefulness of the sputum Gram stain in diagnosing community-acquired pneumonia. Results of a large prospective study from Spain

Prospective study of the usefulness of sputum Gram stain in the initial approach to community-acquired pneumonia requiring hospitalization.

From February 1995 through May 1997, we prospectively studied 533 patients with community-acquired pneumonia requiring hospitalization in order to assess the current usefulness of sputum Gram stain in guiding the etiologic diagnosis and initial antibiotic therapy when applied routinely. Sputum samples of good quality were obtained in 210 (39%) patients, 175 of whom showed a predominant morphotype. Sensitivity and specificity of Gram stain for the diagnosis of pneumococcal pneumonia were 57% and 97%, respectively; the corresponding values for Haemophilus influenzae pneumonia were 82% and 99%. Patients with a predominant morphotype were more frequently treated with monotherapy than were patients without a demonstrative sputum sample (89% vs. 75%; P<.001). Analysis of our data shows that a good-quality sputum sample can be obtained from a substantial number of patients with community-acquired pneumonia. Gram stain was highly specific for the diagnosis of pneumococcal and H. influenzae pneumonia and may be useful in guiding pathogen-oriented antimicrobial therapy.

The Reproducibility of Sputum Gram Film Interpretation

Objectives: To evaluate the reproducibility with which microbiologists interpret Gram-stained sputa and examine the effect of the smear preparation method.Methods: Two hundred and ten coded slides prepared directly from a purulent portion of sputum (DS) and 140 slides prepared after homogenization of the same sputum (HS) were examined by three experienced microbiologists. Aproportion of the slides prepared by each method were recoded and represented to the raters. Intraobserver andinterobserver variation was assessed using the kappa statistic (κ).Results: Evaluation of the smear as being infected and predicting Streptococcus pneumoniae as the infecting organism showed the greatest intraobserver agreement (κ=0.74–0.82) and interobserver agreement (κ=0.50–0.82). The agreement concerning the number of cells and infection with Haemophilus influenzae was only fair to moderate. Differences in the interpretation of smears prepared by the two methods could be explained by the intrinsic disagreement that occurs when the same smear is examined twice. The positive predictive value of a positive S. pneumoniae smear for a positive culture ([106/ml) was 81% with the DS and 97% with the HS.Conclusion: In this laboratory, a sputum Gram film interpretation suggesting infection with S. pneumoniae wasreproducible and predictive of a significant positive culture.

Where do developing world clinicians obtain evidence for practice: A case study on pneumonia

There are few data on the practice of evidence based medicine in the developing world, nor on the actual sources of evidence that clinicians use in practice. To test the hypothesis that there was variation between and within developing countries in the proposed management of a patient with hospital acquired pneumonia, and that part of the variation can be explained by the sources of evidence used. Questionnaire responses to hypothetical case history. Investigators from 6 centres within the International Clinical Epidemiology Network (INCLEN) in China, Thailand, India, Egypt, and Kenya. Doctors chosen to represent primary and secondary hospital practice in the regions of the study centres. Investigations and initial treatments which would be ordered for a hypothetical 60-year-old woman who develops pneumonia 5 days after hospital admission, whether local data on antibiotic sensitivities are available and where information would be obtained to guide management. Chest x-ray and sputum gram stain/culture were consistently the most commonly ordered investigations, there being much greater variation in the initial treatment choices with either penicillin, a third-generation cephalosporin or aminoglycoside being the most popular choice. Textbooks were the commonest form of information source, and access to a library, textbooks and journals were statistically significantly associated with appropriate choice of investigations, but not treatment. Access to local antibiotic sensitivities was associated with appropriate initial treatment choice. Improving access to information in the literature and to local data may increase the practice of evidence-based medicine in the developing world.

Cavitating lung lesion and hemoptysis in a young woman

In February 1996, an 18-year-old girl was admitted to hospital with hemoptysis and a local lesion in the right lower lobe. She was asymptomatic until December 1995, when she developed an unproductive cough. She had dental caries, and 1 month later presented periodontitis and was treated with antibiotics. On admission, she was apyrexial, and chest radiography showed cavitationwithin the right lower lobe. Zhiel^Neelsen staining was negative in several sputum smears, and oropharyngeal contamination was observed on sputum Gram stain. Tuberculin test was negative. A diagnosis of lung abscess was made, and she initially received amoxycillin^clavulanate. Hemoptysis disappeared, lung cavitation reduced and she was discharged. Three months later the pulmonary lesion remained, although the patient was asymptomatic. In June 1996, hemoptysis reappeared and the chest radiography worsened. Bronchoscopic examination showed no endobronchial lesions, and the Zhiel^Neelsen staining and the Lo« wenstein culture of the bronchoalveolar lavage (BAL) were negative. Furthermore, BAL contained no malignant cells. Computed tomographywas performed and is shown above.

BACTERIOLOGICAL ERADICATION OF STREPTOCOCCUS PNEUMONIAE FROM PATIENTS WITH ACUTE EXACERBATIONS OF CHRONIC BRONCHITIS: CEFUROXIME AXETIL VERSUS CEFIXIME

SUMMARYThe bacteriological eradication rates of Streptococcus pneumoniae from sputum of patients experiencing acute exacerbations of chronic bronchitis (WHO definition) have been compared following therapy with either cefuroxime axetil 250 mg b.d. or cefixime 200 mg b.d. All patients were hospitalised for an acute exacerbation of chronic bronchitis. The study design was a multicentre, double‐blind, randomised, parallel group with patients giving written informed consent initially. Patients were recruited to the study if they met the WHO definition of chronic bronchitis, were aged 30‐75 years and had a high probability of S. pneumoniae infection based on initial sputum Gram stain. All S. pneumoniae isolates were serotyped and susceptibility tested at the National Reference Centre, Paris. S. pneumoniae was eradicated more rapidly following cefuroxime axetil administration than after cefixime and this difference was statistically significant (p=0.002) at 2‐4 days post‐treatment. Clinical endpoints showed a similar trend – 94% response to cefuroxime axetil compared with 71% response to cefixime (RR 6.39:1). Cefuroxime eradicated S. pneumoniae significantly more rapidly than cefixime and patients in the cefuroxime axetil arm had favourable clinical criteria. The data suggest that focused antibacterial studies may be helpful in evaluating antibiotics in acute exacerbation of chronic bronchitis.

Treatment of Community-Acquired Pneumonia— IDSA Guidelines

The Infectious Diseases Society of America (IDSA) has published guidelines for the treatment of community-acquired pneumonia (CAP). Although Streptococcus pneumoniae remains the most common etiologic agent, Chlamydia pneumoniae and Legionella pneumophila are also important causes. For all suspected CAP patients, particularly those requiring hospitalization, chest radiographs are strongly recommended to confirm the diagnosis. The IDSA guidelines, in contrast to those published by the American Thoracic Society, emphasize the use of sputum Gram's stain and culture in all patients, whenever possible, to establish etiology. This information can be used not only to guide therapy but also to track trends in the etiologic pathogens for CAP and their antibiotic susceptibility. In light of the better outcomes with the earliest possible interventions, the IDSA recommends initial empiric antimicrobial therapy until laboratory results can be obtained to guide more specific therapy. Macrolides, doxycycline, and fluoroquinolones are suggested for primary empiric therapy, since each has activity against common bacterial pathogens and atypical agents. Detailed antibiotic recommendations are made for various pathogens. For inpatients, attempts should be made to cover Legionella and other common pathogenic bacteria. Alternative antibiotics are recommended for patients with structural diseases of the lung, penicillin allergy, or suspected aspiration pneumonia. Switch to an appropriate oral antibiotic is recommended as soon as the patient's condition is stable and he or she can tolerate oral therapy, often within 72 h.

Community-Acquired Pneumonia: An Overview.

Community-acquired pneumonia (CAP) accounts for a significant number of hospitalizations and outpatient visits, as well as substantial health care expenditures. CAP is particularly common among the elderly who account for more than 90% of deaths due to pneumonia. Streptococcus pneumoniae is believed to be the most common microbial etiology of CAP, but recent studies suggest that the atypical pathogens may be more common than previously thought, particularly among ambulatory patients. Recent studies have provided data regarding risk of mortality and process of care and outcomes. Increasing resistance among strains of S. pneumoniae has impacted the approach to the empiric therapy of CAP. The Infectious Diseases Society of America published guidelines for the evaluation and management of CAP this past year. Pathogen-specific therapy guided by the results of sputum gram stain and culture is emphasized. Despite enthusiasm for practice guidelines and clinical pathways, there remains insufficient published data to determine their impact on quality and cost of care in patients with CAP.