Cefoperazone versus combination antibiotic therapy of hospital-acquired pneumonia

Cefoperazone monotherapy was compared with combination antibiotic therapy in a randomized prospective evaluation of patients with hospital-acquired pneumonia. Cefoperazone was as effective as either clindamycin/gentamicin or cefazolin/gentamicin (cure rate: 45 of 52 cefoperazone-treated patients [87 percent], versus 44 of 61 combination-therapy patients [72 percent], p = 0.069). With the exception of hypoprothrombinemia in those patients who did not receive prophylactic vitamin K, there was no difference in the incidence of side effects. In addition, no difference was noted in the incidence of superinfections or secondary pneumonias. When antibiotic costs, administration costs, and laboratory costs were considered, cefoperazone monotherapy was the least expensive antibiotic regimen. Cefoperazone is a suitable alternative to combination antibiotic therapy for the treatment of hospital-acquired pneumonia.     

Associations between initial antimicrobial therapy and medical outcomes for hospitalized elderly patients with pneumonia

BACKGROUND: Although medical practice guidelines exist, there have been no large-scale studies assessing the relationship between initial antimicrobial therapy and medical outcomes for patients hospitalized with pneumonia. OBJECTIVE: To determine the associations between initial antimicrobial therapy and 30-day mortality for these patients. METHODS: Hospital records for 12945 Medicare inpatients (> or = 65 years of age) with pneumonia were reviewed. Associations between initial antimicrobial regimens and 30-day mortality were assessed with Cox proportional hazards models, adjusting for baseline differences in patient characteristics, illness severity, and processes of care. Comparisons were made with patients treated with a non-pseudomonal third-generation cephalosporin alone (the reference group). RESULTS: Initial treatment with a second-generation cephalosporin plus macrolide (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52-0.96), a non-pseudomonal third-generation cephalosporin plus macrolide (HR, 0.74; 95% CI, 0.60-0.92), or a fluoroquinolone alone (HR, 0.64; 95% CI, 0.43-0.94) was independently associated with lower 30-day mortality. Adjusted mortality among patients initially treated with these 3 regimens became significantly lower than that in the reference group beginning 2, 3, and 7 days, respectively, after hospital admission. Use of a beta-lactam/beta-lactamase inhibitor plus macrolide (HR, 1.77; 95% CI, 1.28-2.46) and an aminoglycoside plus another agent (HR, 1.21; 95% CI, 1.02-1.43) were associated with an increased 30-day mortality. CONCLUSIONS: In this study of primarily community-dwelling elderly patients hospitalized with pneumonia, 3 initial empiric antimicrobial regimens were independently associated with a lower 30-day mortality. The more widespread use of these antimicrobial regimens is likely to improve the medical outcomes for elderly patients with pneumonia.     

Effectiveness of combination therapy versus monotherapy with a third-generation cephalosporin in bacteraemic pneumococcal pneumonia: A propensity score analysis

Objective

Combining a macrolide or a fluoroquinolone to beta-lactam regimens in the treatment of patients with moderate to severe community-acquired pneumonia is recommended by the international guidelines. However, the information in patients with bacteraemic pneumococcal pneumonia is limited.

Cefamandole and cefoxitin

Cefamandole and cefoxitin, introduced only 7 years ago, are now the most commonly prescribed parenteral antibiotics in the United States. These drugs are similar to the first-generation cephalosporins in toxicity, but their in-vitro spectrum of activity is greater. Their serum half-lives are longer than those of cephalothin and cephapirin but shorter than that of cefazolin. Although cefamandole has been recommended in empiric therapy for patients with community-acquired pneumonia and as a prophylactic agent for patients having various surgical procedures, other regimens are less expensive and just as effective. Cefamandole should not be used to treat intra-abdominal, enterobacter, or ampicillin-resistant Haemophilus influenzae infections. Cefoxitin is effective in the treatment and prevention of mixed aerobic-anaerobic skin and soft-tissue, intra-abdominal, gynecologic, and penicillinase-producing, spectinomycin-resistant Neisseria gonorrhoeae infections. Cefoxitin represents a greater advance than cefamandole in our continuing search for safe and more effective antimicrobial agents.     

The prediction of streptococcal pharyngitis in adults

The usefulness of clinical and laboratory findings for prediction of the presence of Group A streptococci on throat culture and of an increase in antistreptococcal antibodies was investigated in 693 adult patients. Several findings were shown to increase the likelihood of streptococcal isolation, alone and in combination: tonsillar exudate, tonsillar enlargement, tender anterior cervical adenopathy, myalgias, and a positive throat culture in the preceding year. Compared with a frequency of 9.7% in all patients, the probabilities of a positive culture were quite different (ranging from 2 to 53%) in subgroups of patients with different combinations of these clinical findings. The results of a leukocyte count and measurement of C-reactive protein added little additional predictive information. While clinical findings can never predict perfectly the results of a throat culture, they nevertheless can provide useful information — particularly in tending to “rule out” streptococcal infection — in adult patients with pharyngitis. Received from the Divisions of General Medicine and Primary Care, Joint Department of Medicine, Brigham and Women’s Hospital and Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts: the Charles A. Dana Research Center and the Harvard-Thorndike Laboratory: the Institute for Health Research, Harvard School of Public Health: the Harvard Community Health Plan (Kenmore Branch), Boston, Massachusetts; and the Rhode Island Group Health Association, Providence, Rhode Island. Supported by grants from the National Center for Health Services Research (HS 02063 and HS 04066) and grants from the Commonwealth Fund, and the Robert Wood Johnson Foundation.     

Vibrio vulnificus infection in Taiwan: report of 28 cases and review of clinical manifestations and treatment.

From May 1985 through July 1990, 28 episodes of Vibrio vulnificus infection in 27 patients were encountered in five major hospitals in Taiwan. The ages of patients ranged from 19 to 76 years; the ratio of male to female patients was 2:1. Eighteen episodes manifested as bacteremia and eight as wound infections alone. One patient each developed gastroenteritis and pneumonia after nearly drowning. Twenty-three patients exhibited skin manifestations. Twenty patients had underlying diseases. All patients were treated with antibiotics, and 14 also underwent some form of surgical treatment (incision and drainage, fasciotomy, debridement, or amputation). Thirteen of the 28 episodes were preceded by precipitating factors; most were due to ingestion of seafood or exposure of abraded skin to salt water. Ten of the 18 septicemic patients died--most within 48 hours of hospitalization. One patient without bacteremia who had a wound infection died. Results of in vitro susceptibility studies suggested that ampicillin or a third-generation cephalosporin would be effective. Susceptibility to aminoglycosides was observed for greater than 90% of isolates. We recommend combined therapy with a third-generation cephalosporin or ampicillin and an aminoglycoside along with appropriate surgical therapy for the treatment of V. vulnificus infection.     

Imipenem/cilastatin versus gentamicin/clindamycin: a cost effectiveness study

A previously published clinical trial was used for analysis of costs for antibiotic treatment in patients with serious bacterial infections requiring the use of injectable broad spectrum antibiotics. The patients were randomized to receive imipenem/cilastatin 500/500 mg q6h (77 patients of which 56 were evaluable for efficacy) or clindamycin 600 mg q6h plus gentamicin 1.5 mg/kg with dose intervals determined by serum concentration monitoring (86 patients of which 62 were evaluable for efficacy). An analysis of the costs for antibiotics, including drugs, equipment and staff for administration and gentamicin serum concentration assays, showed that imipenem/cilastatin was not more expensive than gentamicin plus clindamycin per treatment day although the drug cost was considerably higher for imipenem/cilastatin. Since imipenem/cilastatin was significantly more effective and caused less frequent adverse reactions than gentamicin plus clindamycin it was more cost-effective in the patients studied.     

Impact of antibiotic resistance on the treatment of sepsis

Antibiotics are essential to the treatment of bacterial sepsis as they reduce the bacterial burden. The impact of bacterial resistance has recently been studied and found to be important in a range of conditions. Resistance to antibiotics can be defined genotypically, phenotypically and clinically through pharmacokinetic/pharmacodynamic studies and their correlations with clinical outcomes. Although the kinetics of antibiotics has been shown to be favourably altered in sepsis, a range of studies in sepsis has revealed that for most pathogens resistance contributes to significant increases in mortality. This has been clearly demonstrated in bacteraemia, including community- and hospital-acquired infection, and with bacteraemia caused by vancomycin-resistant enterococci, methicillin-resistant staphylococci and extended-spectrum producing Gram-negative bacteria. Significant mortality increases have also been seen with ventilator-associated pneumonia and serious infections requiring admission to intensive care. Gentotypic and phenotypic resistance in coagulase-negative staphylococci causing bacteraemia, and in invasive pneumococcal disease has not shown differences in mortality. In the latter case, dosage regimens have to date been adequate to overcome laboratory-defined resistance. Early indications are that de-escalating therapy from broad-spectrum initial coverage after results of cultures and susceptibility tests become available does not jeopardize outcomes, and further prospective studies are warranted. There is now convincing evidence that broad-spectrum initial therapy to cover the likely pathogens and their resistances pending culture results is mandatory in sepsis to minimize adverse outcomes.     

Clinical utility of in situ hybridization for diagnosing respiratory tract infection and sepsis

We studied the clinical utility of in situ hybridization (Hybrisep) in diagnosing respiratory infection and/ or sepsis. Peripheral blood was taken from patients with respiratory infections and suspected sepsis for both routine blood culture and in situ hybridization, and focal samples including sputum, bronchoalveolar lavage, and central and thoracic catheter, were simultaneously examined for bacterial culture. Specimens numbered 46. The clinical diagnosis was 20 cases of septicemia, with 26 specimens diagnosed as respiratory infectious diseases including hospital-acquired pneumonia and pleurisy. Positive cases of in situ hybridization were seen in 19 specimens (41.3%) in all specimens, significantly higher than that in blood culture (17.4%). Respiratory infection showed a high positive rate in in situ hybridization. Interestingly, the bacterial pathogen detected by in situ hybridization was not always consistent with that taken from focal samples. Whether the pathogen isolated by in situ hybridization is accurate etiologically or diagnostically remains unknown, but our findings suggest a polymicrobial infection in patients with hospital-acquired respiratory infections. In situ hybridization thus provides important information on the etiological pathogen in different infectious diseases.     

Enterococcal pneumonia. Occurrence in patients receiving broad-spectrum antibiotic regimens and enteral feeding

Enterococcal pneumonia occurred as a superinfection in two patients who received broad-spectrum antibiotic therapy. Both patients were receiving enteral hyperalimentation by Dobb-Hoff tube. The organism was isolated from transtracheal aspirate in pure culture and gram-positive cocci were visible on gram-stained smear. Enterococcal pneumonia may occur in patients receiving cephalosporin-aminoglycoside therapy, and may be anticipated as a consequence of third-generation cephalosporin therapy.     

Infections associated with biliary drainage procedures in patients with cancer

A total of 170 therapeutic biliary drainage procedures were carried out in 90 patients with cancer over a 1-year period (January-December 1988). There were 129 percutaneous transhepatic biliary drainage procedures done in 61 patients and 41 endoprostheses were placed in 29 patients. The overall infection rate related to these procedures was 60.6%, the rate being similar for the two procedures. Infectious complications were experienced by 50% of patients undergoing a biliary drainage procedure. The most common manifestation was cholangitis followed by bacteremia. Other infections included liver abscess, gallbladder abscess, and subphrenic abscess. The most common isolates were enteric gram-negative bacilli, followed by Enterococcus species, Candida species, and Staphylococcus epidermidis. The use of prophylactic antibiotics in 76% of infected patients failed to prevent biliary catheter-related infections. Two patients died of complications related to biliary sepsis. All other infected patients responded to antimicrobial therapy, which included various regimens of beta-lactam agents (third-generation cephalosporin, extended-spectrum penicillin, imipenem-cilastatin, and aztreonam) that were used in combination with an aminoglycoside in 15 patients.     

Antibiotic agents in the elderly

Changes that occur in the pharmacology of drugs in the elderly must be considered in the use of antimicrobial agents. Although absorption of orally administered drugs is not affected in a significant way, renal function decreases, drug-drug interactions increase, compliance with regimens may be decreased, and drug toxicity is increased. The most frequent infections occurring in the elderly are pneumonia, urinary tract infection, and soft-tissue infection. CDAD is usually a complication of antibiotic therapy. Pneumonia can be categorized as community-acquired, LTCF, and hospital-acquired. Therapeutic approaches vary according to which of these sites is involved. Urinary tract infection is divided into upper tract infection, lower tract infection, and asymptomatic bacteriuria. Upper tract infection is treated for a longer period than lower tract infection; with few exceptions, asymptomatic bacteriuria is usually not treated. Soft-tissue infection is usually caused by an infected pressure ulcer or cellulitis (which may be a complication of a diabetic foot ulcer or an ulcer due to peripheral vascular disease). These infections have different microbial causes and require different therapeutic approaches.     

Implementation of preventive services in an HMO practice

Practice does not conform to guidelines unless the guidelines are specifically implemented and performance is monitored. Several examples of implementation in one health maintenance organization (HMO) are given. These include immunization for influenza and follow up of positive screening tests for colorectal and cervical cancer. Each implementation effort has required the development of systems, which in this HMO are automated. Several issues influencing implementation are discussed, including resource constraints and priorities for the allocation of new resources. Developers cannot expect that their guidelines will be incorporated into clinical practice. They must foster specific implementation plans. Received from the Harvard Community Health Plan, 10 Brookline Place West, Brookline, Massachusetts 02146.     

New therapeutic approaches to hospital-acquired pneumonia

Conventional therapy of hospital-acquired pneumonia includes intravenous antibiotics and supportive care. In many cases, the etiologic agent of infection is not clear; thus, empiric broad-spectrum antibiotic regimens are commonly used. Combinations of beta-lactam and aminoglycoside agents are particularly popular regimens due to the high incidence of gram-negative bacillary and Staphylococcus aureus pneumonias in the hospital setting. Several new approaches to treatment of nosocomial pneumonias are currently being evaluated, however. These include: single-agent empiric coverage using a broad-spectrum beta-lactam agent; intrabronchial aminoglycoside instillation therapy; oral quinolone agents for treatment of gram-negative bacillary pneumonia; and passive immune therapy. The current experience and potential future role of these therapeutic options are discussed in this chapter.     

A 20-year epidemiological study of pneumococcal meningitis.

We conducted a retrospective analysis of 55 community-acquired Streptococcus pneumoniae meningitis illnesses in Huntington, West Virginia, from 1978 to 1997. Fourteen (36.8%) of 38 adults and 2 (11.8%) of 17 children died. Serotypes 6, 23, 3, and 18 accounted for 20 (41.7%) of 48 strains available for serotyping. Of 40 strains available for antimicrobial susceptibility testing, 1 serotype 19 and 1 serotype 23 strain showed intermediate resistance and a second serotype 23 strain showed high resistance to penicillin; all three patients survived. The case-fatality rates among adults who received penicillin alone, gentamicin in combination, or vancomycin and cephalosporin together were 57.1%, 55.5%, and 60%, respectively, and among those who received chloramphenicol or a third-generation cephalosporin, they were 11.1% or nil, respectively. No child died who received chloramphenicol or vancomycin. Two (33%) of 6 children died who received a third-generation cephalosporin; both were critically ill when initially treated. No child and one adult had received pneumococcal vaccine prior to becoming ill.     

Experimental Pseudomonas pneumonia in leukopenic dogs: comparison of therapy with antibiotics and granulocyte transfusions

Pseudomonas aeruginosa pneumonia was produced in dogs with radiation- induced leukopenia to study the comparative efficacy of several different therapies. In a randomized control trial, five treatment regimens were compared: no antibiotics or granulocytes (controls), gentamicin (5 mg/kg/day), carbenicillin (500 mg/kg/day), gentamicin and carbenicillin (same dosages), and daily granulocyte transfusion (minimum 5 x 10(9) cells/day) plus gentamicin (5 mg/kg/day). The most effective therapy was gentamicin plus granulocyte transfusions. Gentamicin alone was not significantly better than no specific therapy. Carbenicillin with or without gentamicin gave intermediate results. This study further supports the utility of granulocyte replacement therapy of infections in severely granulocytopenic subjects. The results also indicate that the relative value of granulocyte transfusions depends upon the specific antibiotic regimen with which these transfusions are compared.     

The effect of vancomycin and third-generation cephalosporins on prevalence of vancomycin-resistant enterococci in 126 U.S. adult intensive care units

BACKGROUND: Patient-specific risk factors for acquisition of vancomycin-resistant enterococci (VRE) among hospitalized patients are becoming well defined. However, few studies have reported data on the institutional risk factors, including rates of antimicrobial use, that predict rates of VRE. Identifying modifiable institutional factors can advance quality-improvement efforts to minimize hospital-acquired infections with VRE. OBJECTIVE: To determine the independent importance of any association between antimicrobial use and risk factors for nosocomial infection on rates of VRE in intensive care units (ICUs). DESIGN: Prospective ecologic study. SETTING: 126 adult ICUs from 60 U.S. hospitals from January 1996 through July 1999. PATIENTS: All patients admitted to participating ICUs. MEASUREMENTS: Monthly use of antimicrobial agents (defined daily doses per 1000 patient-days), nosocomial infection rates, and susceptibilities of all tested enterococci isolated from clinical cultures. RESULTS: Prevalence of VRE (median, 10%; range, 0% to 59%) varied by type of ICU and by teaching status and size of the hospital. Prevalence of VRE was strongly associated with VRE prevalence among inpatient non-ICU areas and outpatient areas in the hospital, ventilator-days per 1000 patient-days, and rate of parenteral vancomycin use. In a weighted linear regression model controlling for type of ICU and rates of VRE among non-ICU inpatient areas, rates of vancomycin use (P < 0.001) and third-generation cephalosporin use (P = 0.02) were independently associated with VRE prevalence. CONCLUSIONS: Higher rates of vancomycin or third-generation cephalosporin use were associated with increased prevalence of VRE, independent of other ICU characteristics and the endemic VRE prevalence elsewhere in the hospital. Decreasing the use rates of these antimicrobial agents could reduce rates of VRE in ICUs.     

Prognostic and risk factors in patients hospitalized with bacterial pneumonia

We studied 316 adults with community-and hospital-acquired bacterial pneumonia admitted from January 1998 to July 2003. Of these, 66 (20.9%) died. Classified by age, none under 70 died, but mortality increased to 22.6% in the 70-79 age group, 31.6% in the 80-89 age group and 24.2% in the group over 90. Mortality was 3.4% (6/177) for mild pneumonia, 32.0% (24/75) for moderate pneumonia, and 56.3% (36/64) for severe pneumonia. Mortality in hospital-acquired pneumonia (69.1%) was significantly higher than that in community-acquired pneumonia (10.7%). This may result from the higher percentage of moderate by and severe by ill patients who contracted hospital-acquired pneumonia, since 80% of those with hospital-acquired pneumonia were in the moderate and severe group compared to 36.4% of those with community-acquired pneumonia. For antibiotic regimens, mortality was 18.2% to 36.4% for patients who underwent Penicillins-Cephems therapy compared with 51.6% to 66.7% for Carbapenems-Quinolones therapy. The reasons for these differences remain unclear. Our study indicates that severity of illness, age, and antibiotic therapy were factors correlated with death from pneumonia. Underlying diseases such as respiratory failure, chronic heart failure, cerebrovascular disease, renal failure, malignancy, and senile dementia may also be associated with mortality.     

Perforated and gangrenous appendicitis: an analysis of antibiotic failures

The relationships between resistant pathogens, serum levels of gentamicin, and the outcomes of gangrenous or perforated appendicitis were analyzed in 147 patients. Failure to cure the infection occurred significantly more frequently among patients treated with cefoperazone or cefamandole than among those treated with clindamycin and gentamicin in combination. The failures were associated with recovery of resistant Bacteroides fragilis from intraoperative cultures. Pseudomonas species were also associated with failures, their in vitro susceptibility not correlating with clinical cure. Patients with gentamicin peak serum levels of less than 6 micrograms/ml in the first three days were not more likely to be associated with failure than were patients with higher levels. These clinical observations indicate that antibiotic therapy of intra-abdominal sepsis should include antibiotics with in vitro activity against B fragilis and that precise adjustments of gentamicin levels may not improve outcome. In addition, Pseudomonas species may play a significant role in some of these infections.     

Prognostic factors and antibiotics in Vibrio vulnificus septicemia

BACKGROUND: Immunocompromised patients with Vibrio vulnificus septicemia are at high risk for fatality. When a hemorrhagic bullous necrotic cutaneous lesion (HBNCL) and decreased blood pressure develop, approximately 50% of V vulnificus septicemic patients die within 48 hours. This study aimed to evaluate the risk factor(s) for fatality among patients with V vulnificus septicemia, emphasizing the role of prescribed antimicrobial agents in general and the therapeutic efficacy of the combination of a third-generation cephalosporin and tetracycline or its analogue in particular. METHODS: Patients with the diagnosis of V vulnificus infection admitted to 5 large medical centers in Taiwan between 1995 and 2003 were included in this retrospective study. Patients were divided into 2 groups: those without [corrected] HBNCLs (group 1) [corrected] and those with [corrected] HBNCLs (group 2) [corrected]Patients were further divided into subgoups with [corrected] fatalities (fatal subgroup) and those without fatalities (nonfatal subgroup). RESULTS: A total of 93 patients participated in the study. In group 1, the fatal subgroup had higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (P = .006) and a higher proportion of shock at arrival at the medical center (P = .015) than the nonfatal subgroup. In group 2, the effect of a first- or second-generation cephalosporin plus an aminoglycoside was negative (P = .01) and that of combined third-generation cephalosporin and tetracycline or its analogue was positive (P<.001); significant differences were found between the fatal and nonfatal subgroups in the APACHE II score (P<.001), number who were in shock at arrival at the medical center (P = .02), delayed surgical intervention (P = .03), and peripheral leukocytosis (P = .03). Shock at arrival at the medical center (odds ratio [OR], 19.25; 95% confidence interval [CI], 1.768-209.54; P = .02) was an independent risk factor for fatality in patients without HBNCLs. Use of a third-generation cephalosporin and tetracycline or its analogue significantly reduced fatality rates in patients with HBNCLs (OR, 0.037; 95% CI, 0.007-0.192; P<.001). CONCLUSION: Septic shock is a determinant of fatality in patients with V vulnificus septicemia without HBNCLs; our data suggest that the combination of a third-generation cephalosporin and tetracycline or its analogue may be a better choice in antimicrobial treatment of V vulnificus septicemic patients with HBNCLs.