Clinical implications and treatment of multiresistant Streptococcus pneumoniae pneumonia.

Streptococcus pneumoniae is the leading bacterial cause of community-acquired respiratory tract infections. Prior to the 1970s this pathogen was uniformly susceptible to penicillin and most other antimicrobials. However, since the 1990s there has been a significant increase in drug-resistant Streptococcus pneumoniae (DRSP) due, in large part, to increased use of antimicrobials. The clinical significance of this resistance is not definitely established, but appears to be most relevant to specific MICs for specific antimicrobials. Certain beta-lactams (amoxicillin, cefotaxime, ceftriaxone), the respiratory fluoroquinolones, and telithromycin are among several agents that remain effective against DRSP. Continued surveillance studies, appropriate antimicrobial usage campaigns, stratification of patients based on known risk factors for resistance, and vaccination programmes are needed to appropriately manage DRSP and limit its spread.

Infections due to Corynebacterium group D2. Report of a case.

Corynebacterium group D2 is a gram-positive bacillus easily identified in clinical microbiology laboratories. However, this organism is often disregarded as a skin and mucous contaminant. The Spanish literature has recently described Corynebacterium group D2 as a urinary pathogen in a specific patient population. We report a case of Corynebacterium group D2 infection to illustrate the potential pathogenicity and clinical presentation of infection due to this organism in the United States.

Blinded comparison of cefuroxime to cefaclor for lower respiratory tract infections.

Cefuroxime axetil was compared with cefaclor for the therapy for lower respiratory tract infections. Sixty-one patients were randomized to receive the following drug dosages: (1) cefuroxime axetil, 250 mg orally every 12 hours (21 patients); (2) cefuroxime axetil, 500 mg orally every 12 hours (21 patients); and (3) cefaclor, 500 mg orally every eight hours (19 patients). Of these 61 patients, 80% were male, with a mean age of 59.5 years; 56% had acute pneumonia, and the remainder had an acute bronchitis. Causative pathogens included typical respiratory tract pathogens. Overall, 23 of 27 patients with bronchitis were clinically cured at the end of therapy. Thirty-one of 34 pneumonias were clinically cured or improved at the end of therapy; the three pneumonia treatment failures occurred in the lower dose cefuroxime (n = 2) and cefaclor (n = 1) treatment groups. Overall, bacteriologic cure occurred in 86% of patients treated with 500 mg of cefuroxime axetil compared with 60% of cefaclor-treated patients. Adverse clinical effects were uncommon. From this study, it was concluded that cefuroxime given every 12 hours is at least as clinically efficacious as cefaclor; it is a new oral cephalosporin with pharmacologic and bacterial spectrum advantages over many older agents.

Incidence of community-acquired pneumonia requiring hospitalization. Results of a population-based active surveillance Study in Ohio. The Community-Based Pneumonia Incidence Study Group.

BACKGROUND: Pneumonia is the leading cause of death due to infectious diseases in the United States; however, the incidence of most infections causing community-acquired pneumonia in adults is not well defined. METHODS: We evaluated all adults, residing in 2 counties in Ohio, who were hospitalized in 1991 because of community-acquired pneumonia. Information about risk factors, symptoms, and outcome was collected through interview and medical chart review. Serum samples were collected from consenting individuals during the acute and convalescent phases, and specific etiologic diagnoses were assigned based on results of bacteriologic and immunologic tests. RESULTS: The incidence of community-acquired pneumonia requiring hospitalization in the study counties in 1991 was 266.8 per 100,000 population; the overall case-fatality rate was 8.8%. Pneumonia incidence was higher among blacks than whites (337.7/100,000 vs 253.9/ 100,000; P < .001), was higher among males than females (291.4 vs 244.8; P < .001), and increased with age (91.6/100,000 for persons aged < 45 years, 277.2/ 100,000 for persons aged 45-64 years, and 1012.3/ 100,000 for persons aged > or = 65 years; P < .001). Extrapolation from study incidence data showed the projected annual number of cases of community-acquired pneumonia requiring hospitalization in the United States to be 485,000. These data provide previously unavailable estimates of the annual number of cases that are due to Legionella species (8000-18,000), Mycoplasma pneumoniae (18,700-108,000), and Chlamydia pneumoniae (5890-49,700). CONCLUSIONS: These data provide information about the importance of community-acquired pneumonia and the relative and overall impact of specific causes of pneumonia. The study provides a basis for choosing optimal empiric pneumonia therapy, and allows interventions for prevention of pneumonia to be targeted at groups at greatest risk for serious illness and death.

Azithromycin vs cefuroxime plus erythromycin for empirical treatment of community-acquired pneumonia in hospitalized patients: a prospective, randomized, multicenter trial.

OBJECTIVE: To compare the efficacy and safety of azithromycin dihydrate monotherapy with those of a combination of cefuroxime axetil plus erythromycin as empirical therapy for community-acquired pneumonia in hospitalized patients. METHODS: Patients were enrolled in a prospective, randomized, multicenter study. The standard therapy of cefuroxime plus erythromycin was consistent with the American Thoracic Society, Canadian Community-Acquired Pneumonia Consensus Group, and Infectious Disease Society of America consensus guidelines. The doses were intravenous azithromycin (500 mg once daily) followed by oral azithromycin (500 mg once daily), intravenous cefuroxime (750 mg every 8 hours), followed by oral cefuroxime axetil (500 mg twice daily), and erythromycin (500-1000 mg) intravenously or orally every 6 hours. Randomization was stratified by severity of illness and age. Patients who were immunosuppressed or residing in nursing homes were excluded. RESULTS: Data from 145 patients (67 received azithromycin and 78 received cefuroxime plus erythromycin) were evaluable. Streptococcus pneumoniae and Haemophilus influenzae were isolated in 19% (28/145) and 13% (19/145), respectively. The atypical pathogens accounted for 33% (48/145) of the etiologic diagnoses; Legionella pneumophila, Chlamydia pneumoniae, and Mycoplasma pneumoniae were identified in 14% (20/ 145), 10% (15/145), and 9% (13/145), respectively. Clinical cure was achieved in 91% (61/67) of the patients in the azithromycin group and 91% (71/78) in the cefuroxime plus erythromycin group. Adverse events (intravenous catheter site reactions, gastrointestinal tract disturbances) were significantly more common in patients who received cefuroxime plus erythromycin (49% [30/78]) than in patients who received azithromycin (12% [8/67]) (P<.001). CONCLUSIONS: Treatment with azithromycin was as effective as cefuroxime plus erythromycin in the empirical management of community-acquired pneumonia in immunocompetent patients who were hospitalized. Azithromycin was well tolerated.

Risk factors for domestic acquisition of legionnaires disease. Ohio legionnaires Disease Group.

BACKGROUND: Legionnaires disease is a common cause of adult pneumonia. Outbreaks of legionnaires disease have been well described, but little is known about sporadically occurring legionnaires disease, which accounts for most infections. Exposure to contaminated residential water sources is I plausible means of disease acquisition. METHODS: Employing a matched case-control study design in 15 hospitals in 2 Ohio counties, we prospectively enrolled 146 adults diagnosed as having nonepidemic, community-acquired legionnaires disease and compared each with 2 hospital-based control patients, matched for age, sex, and underlying illness category. An interview regarding potential exposures was followed by a home survey that included sampling residential sources for Legionella. Interview and home survey data were analyzed to estimate the risk of acquiring legionnaires disease associated with various exposures. RESULTS: Multivariate analysis showed that a nonmunicipal water supply (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.17-4.37), recent residential plumbing repair (OR, 2.39; 95% CI, 1.10-5.18), and smoking (OR, 3.48; 95% CI, 2.09-5.79) were independent risk factors for legionnaires disease. Univariate analysis suggested that electric (vs gas) water heaters (OR, 1.97; 95% CI, 1.10-3.52), working more than 40 hours weekly (OR, 2.13; 95% CI, 1.12-4.07), and spending nights away from home before illness (OR, 1.68; 95% CI, 1.03-2.74) were additional possible risk factors. Lower chlorine concentrations in potable water and lower water heater temperatures were associated with residential Legionella colonization. CONCLUSIONS: A proportion of sporadic cases of legionnaires disease may be residentially acquired and are associated with domestic potable water and disruptions in residential plumbing systems. Potential strategies to reduce legionnaires disease risk include consistent chlorination of potable water, increasing water heater temperatures, and limiting exposure to aerosols after domestic plumbing repairs.

Amdinocillin plus cefoxitin versus cefoxitin alone in therapy of mixed soft tissue infections (including diabetic foot infections).

In a randomized comparative trial, 45 patients were treated with amdinocillin plus cefoxitin or cefoxitin alone for bacterial soft tissue infections. Most patients were diabetic and had polymicrobial foot infections. The combination of amdinocillin plus cefoxitin was active in vitro against 71 percent of the isolates obtained before therapy as compared with 65 percent for cefoxitin alone. The combination demonstrated synergy for 29 percent of the isolates tested. A satisfactory clinical response occurred in 90 percent and 71 percent of patients treated with the combination regimen and cefoxitin, respectively, (p greater than 0.1). An increase in serum creatinine thought to be due to interstitial nephritis occurred in one patient treated with the combination regimen. The combination of amdinocillin and cefoxitin was effective in mixed soft tissue infections including diabetic foot infections.

Cefmenoxime versus cefoxitin in the treatment of serious bacterial infections.

A comparative study was conducted using cefmenoxime, a new extended spectrum cephalosporin, versus cefoxitin. Entry into the study was based on a computer-generated randomization (two cefmenoxime to one cefoxitin). An intravenous dose of cefmenoxime (0.5 to 1 g every six hours) or cefoxitin (1 to 2 g every six hours) was administered to patients suspected of having serious bacterial infections. Six patients had urinary tract infections. Four who received cefmenoxime, including two with positive blood cultures, had eradication of bacteremia. One of the two who received cefoxitin had significant bacteriuria, and the urine was clear after treatment. Twenty-four patients were treated for lower respiratory tract infections. All 15 patients who received cefmenoxime had clinical and bacteriologic cures. Two of the nine patients who received cefoxitin continued to have the pathogens at the end of the treatment period. Both patients had a neoplasm of the lung. All 11 patients who had soft tissue infections (nine of whom received cefmenoxime) responded well. Both antibiotics were well tolerated.

Diffusibility of the newer cephalosporins into human interstitial fluids.

A skin window technique was used to investigate the ability of three of the newer cephalosporins, moxalactam, cefoperazone, and ceftriaxone, to enter the interstitial fluid of normal, healthy volunteers. Intravenous and intramuscular routes of delivery were compared. The method of delivery did not greatly affect diffusibility with moxalactam and ceftriaxone. Intravenous infusion resulted in greater diffusibility with cefoperazone than did intramuscular injection. Cefoperazone demonstrated the lowest diffusibility of the three test drugs. Ceftriaxone, administered at one-half the dose of cefoperazone and moxalactam, demonstrated the greatest ability to diffuse into interstitial fluid despite its high level of binding to plasma protein. The better diffusibility of ceftriaxone may be explained by a persistently high concentration gradient provided by its long serum half-life. Overall, the results support the concept of the concentration gradient as an important determinant of antibiotic activity.

Levels of amdinocillin in human plasma and interstitial fluid following intravenous administration.

Amdinocillin levels in human plasma and interstitial fluid were studied in 12 human volunteers. The results showed that relatively high levels of amdinocillin were detected in the interstitial fluid. The fluid to plasma ratio of the area under the curve was 0.25. This is consistent with high diffusibility as seen in drugs with a low percentage of protein binding.

Timentin versus piperacillin in the therapy of serious urinary tract infections.

In a comparative study, 47 patients received Timentin, a combination of ticarcillin plus clavulanic acid, or piperacillin to treat serious urinary tract infections. Thirty-nine infections in 38 patients were clinically evaluable (21 in the Timentin-treated group and 18 in the piperacillin-treated group). These included pyelonephritis (10 in the Timentin-treated group and five in the piperacillin-treated group), bladder infections with sepsis (11 in the Timentin-treated group and 11 in the piperacillin-treated group) and bladder infections without fever (two in the piperacillin-treated group). The addition of clavulanic acid to ticarcillin greatly enhanced the susceptibility of five of the 28 evaluable pathogens in the Timentin-treated group (two Escherichia coli isolates, two Staphylococcus aureus isolates, and one Klebsiella pneumoniae isolate). The minimal inhibitory concentrations at which 50 and 90 percent of the bacterial growth was inhibited were 4 and 64 micrograms/ml, respectively, for Timentin, and 4 and 32 micrograms/ml, respectively, for piperacillin. All evaluable patients had a satisfactory symptomatic response at the end of the trial. Of 28 evaluable pathogens treated with Timentin, 18 were eradicated up through the one-week post-therapy evaluation period; of 27 evaluable pathogens treated with piperacillin, 18 were eradicated up through the same time period. Eradicated pathogens included E. coli (six of 13 in the Timentin-treated group and six of 11 in the piperacillin-treated group), other Enterobacteriaceae (three of three in the Timentin-treated group and eight of 10 in the piperacillin-treated group), Pseudomonas aeruginosa (two of four in the piperacillin-treated group), enterococcus (two of three in the Timentin-treated group and two of two in the piperacillin-treated group), staphylococcal species (four of five in the Timentin-treated group), and other organisms (three of four in the Timentin-treated group). Resistance did not develop in any of the persisting pathogens. Adverse effects thought possibly to be related to the study drugs were minimal and included rash in one Timentin-treated patient and diarrhea in another.

Treatment of bacteriuria in pregnancy.

The presence of bacteriuria during gestation increases the chance of acute pyelonephritis. Treatment of bacteriuria in pregnancy reduces subsequent development of symptomatic disease. Numerous studies have shown that single-dose therapy for asymptomatic bacteriuria is as effective as longer course of treatment. Single-dose therapy also has the advantages of improved compliance, reduced costs, and less adverse effects resulting from long term therapy. Follow-up cultures following antimicrobial treatment should be used for early detection of recurrence or relapse. If the urine culture yields no growth, a urine culture at a monthly interval will suffice. If on the other hand bacteriuria is present, a repeat course of antimicrobial therapy should be chosen based on antimicrobial susceptibility testing. A longer course of therapy, possibly with a different drug, is recommended for women with a positive follow-up urine culture. Acute cystitis may be treated with the same regimen as asymptomatic bacteriuria. When upper urinary tract infection is suspected, hospitalisation and a longer course of therapy is recommended. If the organism is susceptible to cefalexin or nitrofurantoin, postcoital prophylaxis with either agent for the remainder of the pregnancy may be beneficial.

Overview of resistance in the 1990s.

The tremendous therapeutic advantage afforded by antibiotics is being threatened by the emergence of increasingly resistant strains of microbes. Selective pressure favoring resistant strains arises from misuse and overuse of antimicrobials (notably extended-spectrum cephalosporins), increased numbers of immunocompromised hosts, lapses in infection control, increased use of invasive procedures and devices, and the widespread use of antibiotics in agriculture and animal husbandry. Outside the hospital, penicillin-resistant Streptococcus pneumoniae is of greatest concern; recent reports also indicate the appearance of outpatient methicillin-resistant Staphylococcus aureus (MRSA) infections. MRSA is a significant problem in the hospital, as are vancomycin-resistant Enterococcus, oxacillin-resistant S aureus, and multidrug-resistant Gram-negative bacilli. Owing to the high rate of antibiotic use and other risk factors, a person is more likely to acquire an antibiotic-resistant infection in the ICU than anywhere else, either inside or outside the hospital. Responsible antibiotic use and stringent infection-control policies are needed to discourage the development of resistant strains.

The radiologic manifestations of Legionnaire's disease. The Ohio Community-Based Pneumonia Incidence Study Group.

STUDY OBJECTIVES: To study the serial radiographic manifestations of Legionnaire's disease from the initial presentation on admission to recovery using strict criteria for the diagnosis of infection. MATERIALS AND METHODS: We prospectively studied the chest radiographs of patients hospitalized with a diagnosis of community-acquired pneumonia in Summit County, Ohio between November 1990 and November 1992. Forty-three patients fulfilled strict criteria for legionellosis. The diagnosis of infection was based on the criteria of "definite" diagnosis as defined by the Ohio Community-Based Pneumonia Incidence Study Group report. The criteria included the isolation of the microorganism, the presence of a significant antibody rise, or the presence of Legionella antigen in the urine. RESULTS: Forty of 43 patients had admission radiographs interpreted as compatible with pneumonia. In spite of appropriate antimicrobial therapy, worsening of the infiltrates was found in more than half of the patients within the first week. Twenty-seven patients were observed to have pleural effusion during the course of hospitalization: 10 effusions were found on admission, another 14 developed during the first week, and 3 new effusions were discovered after the first week. Cavitation was found in only one patient. None of the patients had apical involvement. CONCLUSION: This study confirms previous reports using less stringent etiologic diagnosis criteria that chest radiographic findings in Legionnaire's disease are not specific. Even with appropriate therapy, more than half of the patients will have worsening of the infiltrates during the first week. Pleural effusion is common among our patients, and it is frequently detected during the serial radiographic studies during the first week of hospitalization. Chest radiography in Legionnaire's disease is useful only for the monitoring of disease progression and not for diagnostic purposes. In addition, worsening of infiltrates and pleural effusion are seen in more than half of the patients in spite of appropriate therapy and clinical improvement.

An outbreak of Pseudomonas aeruginosa ventilator-associated respiratory infections due to contaminated food coloring dye--further evidence of the significance of gastric colonization preceding nosocomial pneumonia.

An outbreak of ventilator-associated Pseudomonas aeruginosa respiratory infections in an intensive care unit of a teaching hospital was found to be associated with contaminated food coloring dye. Serotyping and bacteriocin typing indicated that the same strain of Pseudomonas was isolated from the food dye and from the respiratory cultures of the majority of patients. This observation lends credence to the importance of gastric colonization preceding pneumonia in ventilated patients.

Value of noninvasive studies in community-acquired pneumonia.

Noninvasive diagnostic studies, i.e., sputum gram stain, sputum culture, blood culture and antigen detection assays will assist the clinician in the selection of initial antimicrobial therapy in some patients. These tests may be even more valuable in adjusting treatment regimens to prevent the use of broad spectrum antimicrobial agents as routine therapy.

The role of atypical pathogens: Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila in respiratory infection.

Infections caused by M. pneumoniae, C. pneumoniae, and Legionella spp. are important causes of community-acquired pneumonia (CAP). In the past decade, considerable new information has come to light concerning these organisms. Despite this, debate continues concerning the syndromic approach to CAP and the scientific merit of lumping these pathogens together. Because the etiologic diagnosis of these pathogens is established only in a minority of cases, the true prevalence tends to be underestimated. In clinical practice, these pathogens are often empirically treated. More rapid and cost-effective diagnostic techniques are needed so that the clinical course of patients with these infections can be better characterized.

In vitro susceptibility of the Bacteroides fragilis group in community hospitals.

The antimicrobial susceptibility of clinical isolates of the Bacteroides fragilis group was determined at six community hospitals (one large, greater than 600 beds; and five smaller, 96-325 beds). Imipenem was the most active beta-lactam with 100% of isolates being sensitive at 4 micrograms/ml. The percentage of isolates inhibited at 16 micrograms/ml (and 32 micrograms/ml) for the 7-alpha-methoxy antibiotics was: cefoxitin 66 (90); moxalactam 73 (85); cefotetan 68 (72); cefmetazole 40 (61). Metronidazole, chloramphenicol, and clindamycin were active against 100%, 100%, and 89% at breakpoints of 8 micrograms/ml, 8 micrograms/ml, and 4 micrograms/ml, respectively. The activity of several beta-lactams in our report differed slightly from that reported from university teaching hospitals. There were differences at many of the breakpoints for activity of some of the beta-lactam antibiotics for isolates from the large community hospital as compared with the combined isolates from the smaller community hospitals. Interestingly, the pattern was one of more resistance at the smaller community hospitals.

Empiric antimicrobial therapy of serious urinary tract infections.

Parenteral therapy is recommended for empiric treatment of serious urinary tract infections. The approach to antimicrobial selection is reviewed with consideration given to newly available agents.

Clinical evaluation of ceftriaxone.

Seventy-seven patients with acute bacterial infections were treated with ceftriaxone (1 gm administered intravenously every 12 hours). The 58 patients evaluable for efficacy had 60 infections, including 39 of the respiratory tract, 14 of the urinary tract, and seven of soft tissue. Five patients were bacteremic. The mean duration of ceftriaxone treatment was eight days for patients with respiratory and urinary tract infections and 13 days for patients with other types of infections. A satisfactory clinical response occurred in 56 (93%) of the infections. Eighty-four (94%) of the 89 pretherapy pathogens were bacteriologically eradicated. Included were all 19 isolates of Haemophilus influenzae, all 15 of Streptococcus pneumoniae, all 12 of Escherichia coli, 22 of the 23 isolates of other Enterobacteriaceae species, three of five isolates of Pseudomonas aeruginosa, and three of four isolates of Staphylococcus aureus. Two cases of superinfection (one with bacteremia) occurred with P aeruginosa. There were two cases each of reinfection and colonization with Streptococcus faecalis. One patient developed manifestations of culture-documented S pneumoniae meningitis eight hours after the first dose was administered. Peak and trough plasma levels of ceftriaxone were 142 and 64 micrograms/ml. Ceftriaxone achieved therapeutic levels in infected cerebrospinal fluid and in the abscess fluid of selected patients. Adverse effects, which were mild, included diarrhea in 4% of the patients and elevated transaminase levels in 10%.