Initial Empiric Antibiotic Therapy Research Articles

Utility of Gram stain in the clinical management of suspected ventilator-associated pneumonia: Secondary analysis of a multicenter randomized trial

Purpose Gram stains of endotracheal aspirates (EA) and bronchoalveolar lavages (BAL) may guide empiric antibiotic therapy in critically ill patients with suspected ventilator-associated pneumonia (VAP). Previous studies differ regarding the ability of the Gram stain to predict final culture results. The aim of the present study was to evaluate the relationship between EA or BAL Gram stains and final culture results in intensive care unit patients with a suspected VAP. Material and Methods We retrospectively analyzed data from the Canadian multicenter VAP study to correlate EA or BAL Gram stain and final culture results. We categorized Gram stains as Gram positive (GP) and Gram negative (GN) if any GP or GN organisms respectively were seen on staining. Cultures were considered “positive” if they yielded pathogenic organisms on final results. Results Seven hundred forty patients were enrolled in the study; 35 did not have a Gram stain done leaving 350 BALs and 355 EAs from 705 patients. Pooling BAL and EA results, we found the overall agreement between Gram stain class and pathogenic bacteria culture results to be poor ( κ = 0.36; 95% CI, 0.31-0.40). Among specimens with Gram stains showing no organisms, 99 (30%) of 331 grew pathogenic organisms. Among specimens with Gram stains showing no GN organisms, 113 (25%) of 452 grew pathogenic GN organisms. Among specimens with Gram stains showing no GP organisms, 45 (11%) of 428 grew pathogenic GP organisms. Conclusions Gram stains performed for clinically suspected VAP poorly predict the final culture result and thus have a limited role in guiding initial empiric antibiotic therapy in such patients.

Impact of Multiresistance of Gram-negative Bacteria in Bloodstream Infection on Mortality Rates and Length of Stay

Bloodstream infections (BSI) with gram-negative bacteria (GNB) are one of the most serious infections in the hospital setting, a situation compounded by the increasing antibiotic resistance of gram-negative bacteria causing BSI. The aim of the study was to assess the impact of antibiotic multiresistance of GNB in BSI on mortality rates and length of stay (LOS). The setting was the University Hospital Aachen, a 1,500-bed tertiary-care hospital with over 100 ICU beds providing maximal medical care in all disciplines. We performed a 5-year hospital-wide matched cohort study (January 1996 to February 2001) in which 71 cases and 99 controls were enrolled. Matching criteria were sex, age and GNB isolated in blood cultures. Multiresistance was defined as resistance against at least two different classes of antibiotics such as penicillins (+beta-lactamase-inhibitor), third-generation cephalosporins, fluoroquinolones or carbapenems. BSI were mainly nosocomially acquired, and cases of BSI with multiresistant bacteria were associated with a higher mortality (p=0.0418) and a prolonged LOS in the intensive care unit (ICU) (p=0.0049). Risk factors for BSI with multiresistant GNB were antibiotic treatment (p=0.0191) and mechanical ventilation (p=0.0283). Multiresistance of GNB causing BSI was associated with higher mortality rates and longer LOS in ICU. The initial antibiotic therapy was significantly more often inadequate and might have had an impact on overall mortality. Thus, an effective strategy to administer an appropriate initial empirical antibiotic therapy, especially in patients with risk factors, must be sought. Moreover, the overall usage of antimicrobials must be limited and infection control guidelines should be followed to reduce the emergence and transmission of multiresistant GNB.

Health Care–Associated Pneumonia Requiring Hospital Admission

Health care-associated pneumonia (HCAP) has been proposed as a new category of respiratory infection. However, limited data exist to validate this entity. We aimed to ascertain the epidemiology, causative organisms, antibiotic susceptibilities, and outcomes of and empirical antibiotic therapy for HCAP requiring hospitalization. Observational analysis of a prospective cohort of nonseverely immunosuppressed hospitalized adults with pneumonia. Patients who had recent contact with the health care system through nursing homes, home health care programs, hemodialysis clinics, or prior hospitalization were considered to have HCAP. Of 727 cases of pneumonia, 126 (17.3%) were HCAP and 601 (82.7%) were community acquired. Compared with patients with community-acquired pneumonia, patients with HCAP were older (mean age, 69.5 vs 63.7 years; P < .001), had greater comorbidity (95.2% vs 74.7%; P < .001), and were more commonly classified into high-risk pneumonia severity index classes (67.5% vs 48.8%; P < .001). The most common causative organism was Streptococcus pneumoniae in both groups (27.8% vs 33.9%). Drug-resistant pneumococci were more frequently encountered in cases of HCAP. Legionella pneumophila was less common in patients with HCAP (2.4% vs 8.8%; P = .01). Aspiration pneumonia (20.6% vs 3.0%; P < .001), Haemophilus influenzae (11.9% vs 6.0%; P = .02), Staphylococcus aureus (2.4% vs 0%; P = .005), and gram-negative bacilli (4.0% vs 1.0%; P = .03) were more frequent in HCAP. Patients with HCAP more frequently received an initial inappropriate empirical antibiotic therapy (5.6% vs 2.0%; P = .03). The overall case-fatality rate (< 30 days) was higher in patients with HCAP (10.3% vs 4.3%; P = .007). At present, a substantial number of patients initially seen with pneumonia in the emergency department have HCAP. These patients require a targeted approach when selecting empirical antibiotic therapy.

Consequences of inappropriate initial empiric parenteral antibiotic therapy among patients with community-acquired intra-abdominal infections in Spain

To assess the association between inappropriate antibiotic therapy and clinical outcomes for complicated community-acquired intra-abdominal infections in Spain, patient records from October 1998 to August 2002 in 24 hospitals were reviewed. Initial empiric therapy was classified appropriate if all isolates were sensitive to at least 1 of the antibiotics administered. Multivariate analyses were performed to assess associations between appropriateness of therapy and patient outcomes. Healthcare resource use was measured as hospital length of stay (LOS) and d on intravenous antibiotic therapy. A total of 425 patients were included. Of these, 387 (91%) received appropriate initial empiric therapy. Patients on inappropriate therapy were less likely to have clinical success (79% vs 26%, p<0.001), more likely to require additional antibiotic therapy (40% vs 7%, p<0.01) and more likely to be re-hospitalized within 30 d of discharge (18% vs 3%, p<0.01). Multivariate analyses also showed that inappropriate therapy was associated with an almost 16% increase in LOS (p<0.05) and 26% in d of intravenous antibiotic therapy compared with appropriate therapy (p<0.05). Inappropriate initial antibiotic therapy was associated with a significantly higher proportion of unsuccessful patient outcomes (including death, re-operation, re-hospitalization or additional parental antibiotic therapies), increased length of stay and length on therapy.

Pseudomonas aeruginosa Necrotizing Chondritis Complicating High Helical Ear Piercing Case Report

Auricular or high helical ear piercing is an increasingly widespread fashion trend that is associated with an increased risk of potentially serious post-piercing complications such as auricular perichondritis.An 11-year-old girl developed severe auricular perichondritis following piercing of the upper helical cartilage of her ear at a hairdressing salon. Four days post piercing, she returned to the same salon for a haircut during which the pierced site was manipulated. She presented to her family physician and was treated unsuccessfully with oral cephalexin. She was then referred to an infectious diseases consultant and received antipseudomonal intravenous antibiotics with subsequent resolution. She also required debridement and removal of necrotic cartilage. Public health investigation evaluated potential sources of infection including the piercing gun, disinfectant solutions, and hair cutting spray water bottles. Final culture results of the ear helical aspirate grew Pseudomonas aeruginosa. Pseudomonas aeruginosa was also cultured from one of the water bottles used to wet her hair during the haircut.Although the pseudomonal strains from the water bottle were different than the infecting one, this contamination presents a potential source of wound infection. Damage to the helical cartilage caused by the piercing gun may also have contributed to this infection. Initial empiric antibiotic therapy for these kinds of infection must include anti-pseudomonal coverage. Auricular or high helical ear piercing using a piercing gun is not recommended.

Meropenem by Continuous Versus Intermittent Infusion in Ventilator-Associated Pneumonia due to Gram-Negative Bacilli

It is known that beta-lactam antibiotics exhibit time-dependent bactericidal activity. Several studies have found continuous infusion of meropenem more effective than intermittent infusion in maintaining constant serum concentrations in excess of the minimum inhibitory concentration. However, limited data exist on the clinical efficacy of meropenem administered by continuous infusion. To evaluate the clinical efficacy of continuous versus intermittent infusion of meropenem for the treatment of ventilator-associated pneumonia (VAP) due to gram-negative bacilli. A retrospective cohort study was conducted of patients with VAP caused by gram-negative bacilli who received initial empiric antibiotic therapy with meropenem. We analyzed 2 contemporary cohorts: one group received meropenem by continuous infusion (1 g over 360 min every 6 h), the other by intermittent infusion (1 g over 30 min every 6 h). The administration method was prescribed according to the physician's discretion. Patients received meropenem plus tobramycin for 14 days. There were no significant differences between patient groups with regard to gender, age, APACHE-II at intensive care unit admission, diagnosis, microorganism responsible for VAP, or organ dysfunction severity at the time VAP was suspected. The group receiving medication by continuous infusion showed a greater clinical cure rate than the group treated with intermittent infusion (38 of 42, 90.47%, vs 28 of 47, 59.57%, respectively, with OR 6.44 [95% CI 1.97 to 21.05; p < 0.001]). Meropenem administered by continuous infusion may have more clinical efficacy than intermittent infusion.

Selection of an Empiric Antibiotic Regimen for Hospital-Acquired Pneumonia Using a Unit and Culture-Type Specific Antibiogram

The objective of this retrospective study was to determine the optimal initial antibiotic regimen for hospital-acquired pneumonia using the frequency and sensitivity of Gram negative microorganisms found in sputum cultures. An antibiogram was constructed and compared with the hospital intensive care unit (ICU) antibiogram. The results yielded 191 microorganisms. The study-generated antibiogram showed that the highest percent susceptible antibiotics for all Gram-negative microorganisms were imipenem (75%) and amikacin (84%). Considering only Pseudomonas aeruginosa, the study-generated antibiogram and the hospital ICU antibiogram showed similar results, piperacillin and amikacin (86% and 82%, respectively, vs 91% and 85%, P = nonsignificant for both). The optimal empiric antibiotic regimen in the surgical ICU is different if directed against all possible microorganisms as opposed to the most prevalent microorganism P aeruginosa. Determining initial empiric antibiotic therapy using an ICU and culture-type specific antibiogram would result in a greater likelihood that more patients would receive adequate initial antibiotic therapy.

Considerations in the Choice and Administration of Agents for Empiric Antimicrobial Therapy

Background: Infections remain a common problem for critically ill patients and often are responsible for early mortality, especially following inadequate antibiotic therapy. The choice of empiric therapy has become increasingly difficult because of the increasing incidence of antibiotic-resistant bacteria. Methods: A retrospective review of the literature over the last two decades was conducted to assess the importance of adequate empiric antibiotic therapy and which factors should be considered in choosing the “best” empiric therapy. Results: Current diagnostic and treatment guidelines suggest that all seriously ill patients in whom infection is suspected undergo a comprehensive work-up (e.g., blood, urine, sputum cultures) to confirm the etiology prior to initiation of antibiotic therapy. Whereas the selection of the most appropriate antimicrobial agent(s) must consider the likely etiologies and anticipated resistance patterns, the lack of rapid and sensitive culture techniques has made this process difficult. Recent literature has concluded that empiric therapy for many nosocomial infections must be directed at multi-drug-resistant, gram-negative bacilli and methicillinresistant Staphylococcus aureus (MRSA), especially in patients with a history of prolonged hospitalization and recent antibiotic use. There is also growing evidence that inadequate or prolonged antibiotic administration may encourage the emergence of resistant bacteria. New antibiotics directed against multi-drug-resistant, gram-positive pathogens include daptomycin, linezolid, and tigecycline. Conclusions: Initial empiric broad-spectrum antibiotic therapy is necessary for treatment of patients with serious infections following a thorough evaluation of possible sources, including culture and susceptibility testing. Clinicians may need to tailor antibiotic therapy based on the patient's initial response after the organism is confirmed, and susceptibility test results are available.

A systematic approach to diabetic foot infections

Foot infection is the most common reason for hospitalization and subsequent lower extremity amputation among persons with diabetes. Foot ulceration caused by diabetic neuropathy, trauma, and peripheral vascular disease can lead to a limbor life-threatening infection. The optimum treatment of these potentially devastating conditions depends on a multidisciplinary approach that addresses the related or underlying disorders and thus ensures proper wound healing and a positive outcome. In addition to antibiotic therapy, severe soft-tissue or bone infections may necessitate surgical treatment, including drainage, débridement, and vascular reconstruction. Initial (empiric) antibiotic therapy should provide coverage against staphylococci and streptococci and should be revised according culture results. Antibiotic therapy is not indicated in clinically noninfected wounds. The duration of antibiotic treatment can range from 1 week for mild infections to 6 weeks or more for residual osteomyelitis and severe deep tissue infections. Aggressive (and sometimes repeated or staged) surgical intervention and appropriate antibiotic therapy can reduce the likelihood of a major amputation and the duration of hospitalization.

Respiratory nosocomial infections in the medical intensive care unit

Intensive care unit (ICU)-acquired lower respiratory tract infections include acute tracheobronchitis and hospital-acquired and ventilator-associated pneumonia (VAP). Nosocomial pneumonia is the second most common hospital-acquired infection and the leading cause of death in hospital-acquired infections. The mortality rate in VAP ranges from 24% to 76% in several studies. ICU ventilated patients with VAP have a 2- to 10-fold higher risk of death than patients without it. Early oropharyngeal colonization is pivotal in the etiopathogenesis of VAP. The knowledge of risk factors for VAP is important in developing effective preventive programs. Once the physician decides to treat a suspected episode of ICU-acquired pneumonia, some issues should be kept on mind: first, the adequacy of the initial empiric antibiotic therapy; second, the modification of initial inadequate therapy according to microbiological results; third, the benefit of combination therapy; and finally, the duration of the antimicrobial treatment. Additionally, a protocolized work-up to identify the causes of non-response to treatment is mandatory. All these issues are discussed in depth in this article.

Epidemiological and clinical characteristics of occult bacteremia in an adult emergency department in Spain: influence of blood culture results on changes in initial diagnosis and empiric antibiotic treatment

A prospective study was carried out to analyze the usefulness of blood culture results for adult patients who were discharged from the emergency department with bacteremia. Over a 29-month period, 110 patients with significant bacteremia who were seen in the emergency department and discharged home were studied. The mean age of the patients was 61.8 years. The most frequent initial major diagnosis was urinary tract infection (UTI) (n=63; 57.3%). Gram-negative organisms were isolated in 79 (71.8%) cases. A change in diagnosis (44.5% cases) was more common when the initial diagnosis was something other than UTI or when empiric antimicrobial therapy was ineffective or was not given (P<0.001). The significant predictors of modification of the initial empiric antibiotic therapy were ineffective empiric antimicrobial therapy and transfer of the patient from the emergency department to an infectious diseases outpatient clinic (P=0.01). Blood culture results may be useful for achieving the correct diagnosis in adult patients with bacteremia and for guiding treatment in the subsequent management of outpatients.

Inappropriate Initial Empirical Antibiotic Therapy in Abdominal-Surgery Patients

Various investigators have reported unfavorable outcomes for patients with severe infections who have received inappropriate initial empirical

Impact of methicillin resistance on outcome of Staphylococcus aureus ventilator-associated pneumonia.

The impact of methicillin resistance on morbidity and mortality of patients suffering from severe Staphylococcus aureus infections remains highly controversial. We analyzed a retrospective cohort of 97 patients with methicillin-susceptible and 74 patients with methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia (VAP). Initial empiric antibiotic therapy was appropriate for every patient. Patients with methicillin-resistant Staphylococcus aureus VAP were older, had higher disease-severity scores, and had been on mechanical ventilation longer at onset of VAP. Factors associated with 28-day mortality retained by multivariate logistic regression analysis were: age (odds ratio [OR] = 1.05, 95% confidence interval [CI], 1.02-1.08, p = 0.001) and Day 1 organ dysfunctions or infection (ODIN) score (OR = 1.90, 95% CI, 1.31-2.78, p = 0.001), but not methicillin resistance (OR = 1.72, 95% CI, 0.73-4.05, p = 0.22). The percentages of infection relapse or superinfection did not differ significantly between the two patient groups. In conclusion, after controlling for clinical and physiologic heterogeneity between groups, methicillin resistance did not significantly affect 28-day mortality of patients with Staphylococcus aureus VAP receiving appropriate antibiotics.

Pneumopathies du sujet âgé: Évaluation d’un guide de prescription d’antibiothérapie probabiliste dans un service de médecine gériatrique

We developed a prescribing guideline containing recommendations for the initial empirical antibiotic therapy in community or nosocomial pneumonia. The aim of the present study was to examine the impact of this measure. The prescribing guideline was implemented in May 1999. We retrospectively reviewed the charts of all patients>65 years with community-, or nursing home- or hospital-acquired pneumonia hospitalised in our department of acute geriatric care between May 1999 and November 2000. The criteria assessed were: consistence with the guideline, clinical effectiveness within 72 hours, adequation with the isolated germs and intra-hospital mortality. Data were collected on 112 patients (63 women et 49 men; mean age=80 +/- 8 Years). The pneumonia was community-acquired in 52 cases (46%), nursing home acquired in 25 cases (22%) and hospital-acquired in 35 cases (31%). Antibiotic prescription was consistent with the guideline in 64 cases (57%). When the antibiotic therapy was consistent, the patients were more likely to improve within 72 hours (45/64 versus 23/48; p=0.01). Despite a tendency, the number of antimicrobial treatments adapted to the isolated microorganisms was not significantly higher in the consistent group (22/36 adapted treatments versus 10/20). The intra-hospital mortality (25%) was similar in the two groups consistent and not consistent with the guideline. SARM was the most frequent multiresistant bacteria that was isolated. The use of a prescribing guideline might improve the efficiency of empirical probabilistic antibiotic therapies. The impact of the guideline use on overall antibiotic costs and microbiological flora remains to be determined.

The Impact of Methicillin Resistance on the Outcome of Poststernotomy Mediastinitis Due toStaphylococcus aureus

The impact of methicillin resistance on morbidity and mortality among patients with severe Staphylococcus aureus infection remains highly controversial. We retrospectively analyzed patients with mediastinitis due to methicillin-susceptible S. aureus (MSSA; 145 patients) or methicillin-resistant S. aureus (MRSA; 73 patients) who were treated with closed drainage using Redon catheters. Initial empirical antibiotic therapy was appropriate for every patient. Patients with MRSA mediastinitis were older, had higher disease severity scores at admission to the intensive care unit (ICU), and had longer periods of MRSA incubation. Multivariate analysis revealed that ICU mortality was associated with age of > or =65 years, incubation time of < or =15 days, bacteremia, higher Acute Physiology and Chronic Health Evaluation II score, and receipt of mechanical ventilation > or =2 days after surgical debridement, but not with methicillin resistance. After adjustment, durations of mechanical ventilation and Redon catheter drainage were similar for both groups (for patients infected with MRSA, only the time to mediastinal effluent sterilization remained longer). Methicillin resistance did not significantly affect ICU mortality among patients with poststernotomy mediastinitis who benefited from optimal treatments.

Bacteraemic melioidosis pneumonia: impact on outcome, clinical and radiological features.

Melioidosis is an endemic disease in South-east (SE) Asia and bacteraemia in melioidosis is associated with high mortality. We describe some clinical and radiological features of bacteraemic pneumonia due to Burkholderia pseudomallei as well as a comparison with bacteraemic patients without pneumonia. Patients with positive blood cultures for B. pseudomallei from October 1997 to November 2001 were included. Patients were grouped as 'Pneumonia' and 'Non-pneumonia' according to clinical and radiological features. Eighteen (60%) out of total 30 patients were in the pneumonia group. There was no significant difference in age, WBC count, platelet counts and bilirubin levels between the groups. However the 'Pneumonia' group had higher incidences of hyponatraemia, acidosis, diabetes with poor control, renal impairment and shorter length of stay. Twelve (66%) of 18 patients in the pneumonia group required ICU admission compared to none in the non-pneumonia group; all required mechanical ventilation. Only 13/30 (43%) patients had initial empiric antibiotic therapy that is appropriate for melioidosis. The pneumonia group also had significantly higher mortality (13/18, 72%) rate than the non-pneumonia group (3/12, 25%, P=0.03). Chest radiographs were non-specific. 7/18 (38%) had unilobar involvement of the lung, mostly left sided; the rest had multilobar or bilateral involvement. Six (33%) had pleural effusion. No patient had cavitary lung disease. Visceral abscesses (spleen, liver and prostate) were also common in ultrasound and CT scans in both groups. (1) Bacteraemic melioidosis with pneumonia carries high mortality with most patients dying early. (2) Radiological features of melioidosis pneumonia are non-specific. (3) Clinicians who treat patients from SE Asia need to be aware of this condition to institute early and appropriate antibiotic therapy.

Methodology for clinical trials involving patients with cancer who have febrile neutropenia: updated guidelines of the Immunocompromised Host Society/Multinational Association for Supportive Care in Cancer, with emphasis on outpatient studies.

Two multinational organizations, the Immunocompromised Host Society and the Multinational Association for Supportive Care in Cancer, have produced for investigators and regulatory bodies a set of guidelines on methodology for clinical trials involving patients with febrile neutropenia. The guidelines suggest that response (i.e., success of initial empirical antibiotic therapy without any modification) be determined at 72 h and again on day 5, and the reasons for modification should be stated. Blinding and stratification are to be encouraged, as should statistical consideration of trials specifically designed for showing equivalence. Patients enrolled in outpatient studies should be selected by use of a validated risk model, and patients should be carefully monitored after discharge from the hospital. Response and safety parameters should be recorded along with readmission rates. If studies use these guidelines, comparisons between studies will be simpler and will lead to further improvements in patient therapy.

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

Prognostic factors in severe community-acquired pneumonia in patients without co-morbid illness.

We wished to determine the prognostic factors and the impact of initial empirical antibiotic therapy on the outcome of severe community-acquired pneumonia in patients without underlying co-morbid illness. This is a retrospective record review of consecutive patients with severe community-acquired pneumonia who were divided into those with and without underlying co-morbid illness. There were 182 patients including 112 primary (no co-morbid illness) and 70 secondary (underlying co-morbid illness) pneumonias. The overall mortality was 41.8% and there were no differences in APACHE II score or mortality when comparing cases with primary (37.5%) and secondary infections (48.6%). The mortality was significantly higher in patients with negative microbiology. Univariate analysis identified a number of parameters and various antibiotic regimens, which appeared to be associated with a significantly poorer outcome. On multivariate analysis multilobar pulmonary consolidation, need for mechanical ventilation, inotropes and dialysis were documented to be independent predictors of mortality. Only in their absence could different antibiotic regimens be shown to have an apparent impact on outcome and further analysis suggested that the reason for these differences related predominantly to differences in the severity of the infection. Markers of disease severity appear to be the most important predictors of outcome in patients with severe community-acquired pneumonia.

Treatment of Febrile Neutropenia with Cefepime Monotherapy

Background and Objective: The empirical administration of a broad-spectrum β-lactam antibiotic, either as monotherapy or in combination with an aminoglycoside, is an essential component of the initial management of patients with fever and severe neutropenia. Multiple antibiotics have been tested for this indication. Cefepime is a fourth-generation cephalosporin with in vitro activity against most gram-negative and many gram-positive bacteria. We have studied the use of this agent as monotherapy in this indication. Methods: One hundred and twenty-six episodes of febrile neutropenia in 98 adults with hematological malignancies were treated with cefepime monotherapy. Cefepime was given at a dose of 2 g every 8 h i.v. Most episodes (49%) were fever of unexplained origin, while a microbiologically documented and clinically documented infection occurred in 25% episodes each. Seventy-six (61%) episodes occurred after conventional chemotherapy, while 51 (41%) after a hematopoietic stem cell transplantation. Results: Twelve episodes (10%) were not evaluable for response. Among the 114 evaluable episodes, 69 (55% of the initial sample and 61% of those evaluable) responded to cefepime monotherapy, while therapy failed in 45 cases (36% of the initial sample and 39% of those evaluable), including 14 cases who developed breakthrough bacteremia during therapy. There were no deaths due to bacterial infection. At the end of all antibiotic therapy (final outcome) 69 episodes were cured only with monotherapy, 47 were cured with modification of therapy and 10 patients died from an unrelated cause. The only variable that appeared to correlate with response to therapy was the duration of neutropenia, which was longer among patients who failed or developed breakthrough bacteremia than among those who responded to monotherapy. Interpretation and Conclusions: Initial empirical antibiotic therapy with cefepime as a single agent in patients with febrile neutropenia and a hematological malignancy is effective, but patients with prolonged neutropenia appear to be at higher risk for failure. However, with appropriate therapeutic changes the risk of dying from a bacterial infection is very low.