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Antimicrobial regimens consisting of a brief initial period of parenteral therapy followed by oral therapy were investigated in infants and children with suppurative bone and joint disease. There were 30 patients with acute hematogenous disease (19 osteomyelitis; three osteoarthritis; eight arthritis) and five with subacute or chronic osteomyelitis. Disease was due to Staphylococcus aureus in 26, Hemophilus influenzae in five, streptococci in three, and S. aureus plus Streptococcus pyogenes in one patient. Pus was removed by surgical drainage or needle aspiration. Oral therapy was monitored by assay of antibiotic concentration and bactericidal activity in serum. Adjustments in dosage were made when necessary to assure a peak serum bactericidal titer of at least 1:8. One patient progressed to chronic osteomyelitis but all other patients with acute disease responded well. Oral therapy provides increased patient comfort and decreases the risk of nosocomial infection associated with prolonged intravenous therapy. It should be carried out only under carefully monitored conditions in hospital to assure compliance and adequacy of serum bactericidal activity.
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PMID:Oral antibiotic therapy for skeletal infections of children. II. Therapy of osteomyelitis and suppurative arthritis. 63 97

In an open, prospective, multicenter trial the efficacy and tolerance of imipenem/cilastatin for the treatment of bacterial pneumonia was investigated. Forty-three adults were studied: 29 with nosocomial and 14 with community-acquired infections. Significant underlying disease was present in 91 percent of patients. Nosocomial infection was frequently associated with endotracheal intubation (48 percent), prior antibiotic therapy (48 percent), and recent surgery (31 percent). Most frequent sputum isolates included Pseudomonas aeruginosa (10, all nosocomial), Hemophilus influenzae (10), Escherichia coli (eight), Staphylococcus aureus (seven), and Streptococcus pneumoniae (six). Treatment with imipenem/cilastatin was associated with clinical cure in 93 percent of patients. Two of three failures and one superinfection occurred in association with isolates of Pseudomonas aeruginosa resistant to imipenem. Overall, six of 10 strains of Pseudomonas aeruginosa isolated prior to therapy developed resistance to imipenem after an average of 10 days of therapy. Adverse effects occurred in nine patients (21 percent) and included one case of pseudomembranous colitis. Monotherapy with imipenem/cilastatin of serious lower respiratory tract infections was relatively safe and highly effective with the exception of disease associated with P. aeruginosa.
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PMID:Pneumonia treated with imipenem/cilastatin. 385 8

Resistance of nosocomial and community-acquired pathogens to antimicrobial agents is a serious problem with significant clinical consequences. Microbiologic surveillance data, such as those provided by the National Nosocomial Infections Surveillance System, supply information on current nosocomial pathogens in the United States. Many species show resistance to commonly used antimicrobials and, in many cases, it is emerging resistance. Resistance in many gram-negative bacteria is caused by beta-lactamase production. Escherichia coli, the leading nosocomial pathogen, is capable of hyperproducing TEM-1 beta-lactamase. A novel form of resistance in Klebsiella pneumoniae and E. coli is caused by extended-spectrum cephalosporinases. Many Enterobacteriaceae can be induced to produce group 1 beta-lactamase by exposure to broad-spectrum cephalosporins and other beta-lactams. Thirty percent of Haemophilus influenzae isolates are resistant to ampicillin because of beta-lactamase production. Issues of concern in gram-positive species include multiple antimicrobial resistance in methicillin-resistant Staphylococcus aureus, enterococci, and coagulase-negative staphylococci, and increasing beta-lactam resistance in Streptococcus pneumoniae. To minimize the development of resistance, antimicrobials must be administered judiciously, and infection-control practices must be instituted and followed.
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PMID:Trends in antimicrobial resistance among today's bacterial pathogens. 775 90

Pneumonia is the second most frequent cause of nosocomial infection, and hospitalization frequently is needed for community-acquired pneumonia. Knowledge of causative pathogens through periodic surveillance, and their prevailing antimicrobial susceptibility patterns becomes paramount in choosing appropriate empiric therapy. The SENTRY Antimicrobial Surveillance Program, tracks pathogen distribution worldwide since 1997 and documents emerging resistance to a wide range of antimicrobial agents. During the respiratory disease season in 1998, each of 30 medical centers (25 in the United States [US], and five in Canada [CAN]) contributed 100 consecutive isolates obtained from hospitalized patients with suspected pneumonia. The 2773 organisms, processed by the monitor consisted of a total of 35 species, with Staphylococcus aureus comprising 25.6% of all isolates and five other species (Pseudomonas aeruginosa 18.7%, Haemophilus influenzae 9.4%, Streptococcus pneumoniae 7.8%, Klebsiella spp. 7.0%, and Enterobacter spp. 6.7%) making up almost 50% of the total. In the US, pneumococci (8.5%) were more prevalent than in CAN (4.1%; p = 0.001). The US isolates of S. pneumoniae were variably susceptible to penicillin (76.8%), with non-susceptible strains demonstrating greater levels of cross resistance to macrolides (31.8%), cefepime (9.0%) and cefotaxime (6.8%), but remaining susceptible to gatifloxacin and quinupristin/dalfopristin. H. influenzae and Moraxella catarrhalis were generally ampicillin-resistant, 40.4-44.4% and 93.7-95.7%, respectively. P. aeruginosa remained very susceptible to amikacin (91.3-93.8%) > tobramycin > meropenem > piperacillin/tazobactam > gentamicin > piperacillin > cefepime (80.0-81.8%). Extended spectrum beta-lactamase phenotypes among the Klebsiella spp. were isolated from five medical centers in the US and were 4.8-6.0% overall; a rate similar to the previous year. Among the US isolates of Enterobacter spp., only 77.6% and 79.6% were susceptible to ceftazidime and cefotaxime, respectively, but >90% were inhibited by cefepime, imipenem, meropenem, aminoglycosides, and fluoroquinolones. Isolates from CAN were generally more susceptible, except for Pseudomonas isolates, where resistance to aminoglycosides, fluoroquinolones and imipenem was greater. The SENTRY Program results outline important national differences in the frequencies of pathogen occurrence, but more importantly, identify unstable patterns of resistance to available antimicrobial drugs, and serves as a reference for results of other local, national or international investigations.
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PMID:Antibacterial activity of 41 antimicrobials tested against over 2773 bacterial isolates from hospitalized patients with pneumonia: I--results from the SENTRY Antimicrobial Surveillance Program (North America, 1998). 1124 23

OBJECTIVE: To classify infections according to the carrier state determined by surveillance cultures of throat and rectum, rather than by the traditional criterion of the time of onset after admission. METHODS: An observational cohort study of 3 months' duration was performed in a mixed medical---surgical intensive care unit (ICU) in a district general hospital of a subset of patients requiring mechanical ventilation for 3 days. Surveillance cultures from throat and rectum were obtained on admission to the ICU and then twice weekly to distinguish carriage of potentially pathogenic microorganisms (PPM) brought in by the patient from microorganisms acquired during the ICU stay. RESULTS: Out of the total population of 104 patients, 21 patients were enrolled over 3 months. Eight patients (38%) developed 12 infections, half of which were of primary endogenous pathogenesis and caused by Haemophilus influenzae, Candida albicans and Pseudomonas aeruginosa carried by the patients on admission. The remaining six were of secondary endogenous pathogenesis and caused by Acinetobacter baumannii and Pseudomonas aeruginosa acquired in the unit. CONCLUSIONS: Traditional classifications of hospital infection are challenged. If the traditional 48-h cut-off point was used, then 9 of 12 cases (75%) of infection would have been classified as nosocomial, whereas using the method based on the carrier state, 50% of all infections were caused by microorganisms carried by the patient on admission to the ICU. Moreover, we believe that the distinction between primary endogenous, secondary endogenous and exogenous is valid because these three types of infection each require different control methods.
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PMID:Infections in patients requiring ventilation in intensive care: application of a new classification. 1186 93

Ceftriaxone is recommended in children with acute bacterial meningitis (ABM) for 10 days. However, the drug is expensive, and shorter duration of therapy, if equally effective, would cut costs of therapy and hospitalization. The aim of this study was to compare the outcome of 7 days vs. 10 days' ceftriaxone therapy in children with ABM. Seventy-three children aged 3 months to 12 years with ABM, consecutively admitted to hospital were enrolled. Ceftriaxone was given for 7 days to all. Randomization to group I (7 days) and group II (10 days) therapy was done on the seventh day. At the end of 7 days' therapy in group I and 10 days in group II, children were evaluated using a clinical scoring system. Children with a score of more than 10 were labelled as 'treatment failures' and were continued on ceftriaxone. If a score was less than 10, the antibiotic was stopped. Complications were appropriately evaluated and managed. All children were followed-up 1 month after discharge: neurodevelopmental assessment, Denver Development Screening Tests, IQ and hearing assessment were done. After excluding four patients, there were 35 children in group I and 34 in group II. The two groups were comparable with respect to age, sex, nutritional status, presenting clinical features, and CSF parameters. Organism identification was possible in 38 per cent of children: (Streptococcus pneumoniae, 21 per cent; Haemophilus influenzae, 13 per cent; meningococcus, 4 per cent). Treatment failure rate was comparable in both groups (9 in group I and 8 in group II) as was the sequelae at discharge and at 1 month (9 in group I, 15 in group II,p > 0.1). Status epilepticus and focal deficits at presentation were significantly associated with treatment failures and sequelae in both the groups (p < 0.05). Length of hospital stay was shorter in group I (10.8 +/- 6.0 days) as compared with group II (14.4 +/- 7.2 days,p < 0.05) and frequency of nosocomial infection was significantly more in group II (p < 0.05). It was concluded that clinical outcome of patients treated with 7 days' ceftriaxone therapy is similar to that of 10 days' therapy, and is associated with lesser nosocomial infection and earlier hospital discharge. Seven days ceftriaxone therapy may be recommended for uncomplicated ABM in children in developing countries.
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PMID:Seven days vs. 10 days ceftriaxone therapy in bacterial meningitis. 1240 69

The 5th year KONSAR surveillance in 2001 was based on routine test data at 30 participating hospitals. It was of particular interest to find a trend in the resistances of enterococci to vancomycin, of Enterobacteriaceae to the 3rd generation cephalosporin and fluoroquinolone, and of Pseudomonas aeruginosa and acinetobacters to carbapenem. Resistance rates of Gram-positive cocci were: 70% of Staphylococcus aureus to oxacillin; 88% and 16% of Enterococcus faecium to ampicillin and vancomycin, respectively. Seventy-two percent of pneumococci were nonsusceptible to penicillin. The resistance rates of Enterobacteriaceae were: Escherichia coli, 28% to fluoroquinolone; Klebsiella pneumoniae, 27% to ceftazidime, and 20% to cefoxitin; and Enterobacter cloacae, > or =40% to cefotaxime and ceftazidime. The resistance rates of P. aeruginosa were 21% to ceftazidime, 17% to imipenem, and those of the acinetobacters were > or =61% to ceftazidime, aminoglycosides, fluoroquinolone and cotrimoxazole. Thirty-five percent of non-typhoidal salmonellae were ampicillin resistant, and 66% of Haemophilus influenzae were beta-lactamase producers. Notable changes over the 1997-2001 period were: increases in vancomycin-resistant E. faecium, and amikacin- and fluoroquinolone-resistant acinetobacters. With the increasing prevalence of resistant bacteria, nationwide surveillance has become more important for optimal patient management, for the control of nosocomial infection, and for the conservation of the newer antimicrobial agents.
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PMID:Increasing prevalence of vancomycin-resistant Enterococcus faecium, expanded-spectrum cephalosporin-resistant Klebsiella pneumoniae, and imipenem-resistant Pseudomonas aeruginosa in Korea: KONSAR study in 2001. 1496 34

Pulmonary infections span a wide spectrum, ranging from self-limited processes (e.g., tracheobronchitis) to life-threatening infections including both community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). Together, pneumonia and influenza rank as the sixth leading cause of death in the United States and lead all other infectious diseases in this respect. Pneumonia is the second-most-common hospital-acquired infection in the United States, accounting for 17.8% of all hospital-acquired infections and 40,000 to 70,000 deaths per year. HAP is the most common nosocomial infection occurring in patients requiring mechanical ventilation, developing in 6.5% of patients after 10 days and in 28% of patients after 30 days of ventilatory support. Patients acquiring HAP have a greater risk of mortality than comparably ill ventilated patients who do not develop pneumonia. Ventilator-associated pneumonia (VAP) specifically refers to a bacterial pneumonia developing in patients with acute respiratory failure who have been receiving mechanical ventilation for at least 48 hours. The etiologic bacteriologic agents associated with VAP typically differ based on the timing of the occurrence of the infection relative to the start of mechanical ventilation. VAP occurring within 96 hours of the onset of mechanical ventilation is usually due to antibiotic-sensitive bacteria that colonize the patient prior to hospital admission (e.g., Streptococcus pneumoniae, Haemophilus influenza, oxacillin-sensitive Staphylococcus aureus). VAP developing after 96 hours of ventilatory support is more often associated with antibiotic-resistant bacteria including oxacillin-resistant Staphylococcus aureus, Acinetobacter species and Pseudomonas aeruginosa. However, more recent data suggest that hospitalization and exposure to antibiotics prior to the start of mechanical ventilation are important risk factors for the occurrence of VAP attributed to antibiotic-resistant bacteria. Therefore, these risk factors should be considered when deciding on an appropriate empiric antibiotic regimen regardless of the onset of VAP. VAP and catheter-associated bloodstream infections are the leading causes of infection acquired in the intensive care unit (ICU) setting. Patients in the ICU have rates of HAP that are as much as five to ten times higher than the rates in general hospital wards. Additionally, like nosocomial bloodstream infections, VAP is associated with an attributable mortality beyond that accounted for by patients' severity of illness. The attributable mortality associated with VAP appears to be greatest for "high-risk'' antibiotic-resistant bacteria including Pseudomonas aeruginosa and oxacillin-resistant Staphylococcus aureus. The greater hospital mortality associated with these "high-risk'' pathogens has been attributed to the virulence of these bacteria and the increased occurrence of inadequate initial antibiotic treatment of VAP due to the presence of antibiotic resistance. This review provides an overview of the clinical importance of VAP. We then describe how this nosocomial infection influences the management and outcomes of patients with the acute respiratory distress syndrome (ARDS).
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PMID:Ventilator-associated pneumonia complicating the acute respiratory distress syndrome. 1608 83

Nosocomial pneumonia or hospital-acquired pneumonia (HAP) causes considerable morbidity and mortality. It is the second most common nosocomial infection and the leading cause of death from hospital-acquired infections. In 1996 the American Thoracic Society (ATS) published guidelines for empirical therapy of HAP. This review focuses on the literature that has appeared since the ATS statement. Early diagnosis of HAP and its etiology is crucial in guiding empirical therapy. Since 1996, it has become clear that differentiating mere colonization from etiologic pathogens infecting the lower respiratory tract is best achieved by employing bronchoalveolar lavage (BAL) or protected specimen brush (PSB) in combination with quantitative culture and detection of intracellular microorganisms. Endotracheal aspirate and non-bronchoscopic BAL/PSB in combination with quantitative culture provide a good alternative in patients suspected of ventilator-associated pneumonia. Since culture results take 2-3 days, initial therapy of HAP is by definition empirical. Epidemiologic studies have identified the most frequently involved pathogens: Enterobacteriaceae, Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus ('core pathogens'). Empirical therapy covering only the 'core pathogens' will suffice in patients without risk factors for resistant microorganisms. Studies that have appeared since the ATS statement issued in 1996, demonstrate several new risk factors for HAP with multiresistant pathogens. In patients with risk factors, empirical therapy should consist of antibacterials with a broader spectrum. The most important risk factors for resistant microorganisms are late onset of HAP (>/=5 days after admission), recent use of antibacterial therapy, and mechanical ventilation. Multiresistant bacteria of specific interest are methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter calcoaceticus-baumannii, Stenotrophomonas maltophilia and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Each of these organisms has its specific susceptibility pattern, demanding appropriate antibacterial treatment. To further improve outcomes, specific therapeutic options for multiresistant pathogens and pharmacological factors are discussed. Antibacterials developed since 1996 or antibacterials with renewed interest (linezolid, quinupristin/dalfopristin, teicoplanin, meropenem, new fluoroquinolones, and fourth-generation cephalosporins) are discussed in the light of developing resistance.Since the ATS statement, many reports have shown increasing incidences of resistant microorganisms. Therefore, one of the most important conclusions from this review is that empirical therapy for HAP should not be based on general guidelines alone, but that local epidemiology should be taken into account and used in the formulation of local guidelines.
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PMID:Nosocomial pneumonia : rationalizing the approach to empirical therapy. 1640 13

The choice of empirical treatment of nosocomial pneumonia in the intensive-care unit (ICU) used to rely on the interval after the start of mechanical ventilation. Nowadays, however, the question of whether in fact there is a difference in the distribution of causative pathogens is under debate. Data from 308 ICUs from the German National Nosocomial Infection Surveillance System, including information on relevant pathogens isolated in 11,285 cases of nosocomial pneumonia from 1997 to 2004, were used for our evaluation. Each individual pneumonia case was allocated either to early- or to late-onset pneumonia, with three differentiation criteria: onset on the 4th day, the 5th day, or the 7th day in the ICU. The frequency of pathogens was evaluated according to these categories. A total of 5,066 additional cases of pneumonia were reported from 2005 to 2006, after the CDC criteria had been modified. From 1997 to 2004, the most frequent microorganisms were Staphylococcus aureus (2,718 cases, including 720 with methicillin [meticillin]-resistant S. aureus), followed by Pseudomonas aeruginosa (1,837 cases), Klebsiella pneumoniae (1,305 cases), Escherichia coli (1,137 cases), Enterobacter spp. (937 cases), streptococci (671 cases), Haemophilus influenzae (509 cases), Acinetobacter spp. (493 cases), and Stenotrophomonas maltophilia (308 cases). The order of the four most frequent pathogens (accounting for 53.7% of all pathogens) was the same in both groups and was independent of the cutoff categories applied: S. aureus was first, followed by P. aeruginosa, K. pneumoniae, and E. coli. Thus, the predictabilities of the occurrence of pathogens were similar for the earlier (1997-to-2004) and later (2005-to-2006) time frames. This classification is no longer helpful for empirical antibiotic therapy, since the pathogens are the same for both groups.
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PMID:Early- and late-onset pneumonia: is this still a useful classification? 1936 52


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