Rapid differentiation of bacterial meningitides by direct gas-liquid chromatography.

Rapid identification of Haemophilus influenzae and other bacillary meningitides was attempted by gas-liquid chromatography (GLC) of the metabolic by-products in broth cultures and in cerebrospinal fluid (CSF) samples obtained from experimental meningitis produced in New Zealand White male rabbits. These results were correlated with the GLC of CSF of meningitis patients. A major peak with retention time of succinic acid was found in the broth cultures of all bacilli tested including H. influenzae, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter freundii, Pseudomonas aeruginosa, and Listeria monocytogenes. Succinic acid was also found in the CSF of experimental meningitis and in the CSF of all patients with H. influenzae and Esch. coli meningitis. This peak was not detected in the blood samples of experimental animals. It was also absent in the broth cultures of all of the gram-positive and gram-negative cocci tested, such as Streptococcus pneumoniae and Neisseria meningitidis. Succinic acid, which appears to be a by product of fermentation, persisted as a clear cut marker in H. influenzae meningitis for at least 3 d after the initiation of treatment. In one patient, the succinic acid peak disappeared during treatment and reappeared with a clinical relapse. Clearly, the presence of succinic acid that can be rapidly detected by GLC in the CSF excludes pneumococcal or meningococcal meningitis and strongly suggests H. influenzae or other bacillary meningitides.

Rapid diagnosis of anaerobic infections by direct gas-liquid chromatography of clinical speciments.

Current methods to isolate and identify anaerobic bacteria are laborious and time consuming. It was postulated that the short-chain fatty acids (SCFA) produced by these organisms might serve as microbial markers in clinical material. 98 specimens of pus or serous fluid were analyzed by gas-liquid chromatography, and findings were compared with culture results. Good correlations were found for the recovery of anaerobic Gram-negative bacilli and the presence of isobutyric, butyric, and succinic acids. 19 of 20 specimens with significant amounts of these acids (greater than 0.01 mumol/ml) yielded bacteroides or fusobacteria. Culture of the single "false-positive" specimen failed to grow anaerobic Gram-negative bacilli, although clinical data and Gram-stain suggested their presence. 77 of 78 specimens which has insignificant concentrations of the marker acids failed to yield anaerobic, Gram-negative bacilli in culture. The single "false-negative" specimen yielded Bacteroides pneumosintes, an organism which does not ferment carbohydrates. It is concluded that direct gas-liquid chromatographic analysis of clinical specimens provides a rapid presumptive test for the presence of anaerobic, Gram-negative bacilli.

Ticarcillin disodium in anaerobic infections.

Twenty-five patients were treated with ticarcillin disodium, 18 of whom had anaerobic infections that included pleuropulmonary infections (seven), mandibular osteomyelitis (four), perirectal abscess (two), sepsis, primary site unknown (one), liver abscess (one), pelvic abscess (one), decubitus ulcer (one), and synergistic gangrene (one). Seven had no anaerobic infections. Three had anaerobic septicemia. Culture results included anaerobes: peptococci (ten), peptostreptococci (ten), Bacteroides fragilis (six), Bacteroides not fragilis (ten), eubacteria (three), fusobacteria (two), Clostridium (one), Veillonella (one), and acidaminococcus (one); aerobes: Proteus (three), Klebsiella (two), Escherichia coli (two), and streptococci (two). Six patients with mixed aerobic infections initially received gentamicin sulfate in addition. The serum levels were 110 +/- 20 microgram/ml one hour after intravenous infusion of 5 g of ticarcillin disodium. All anaerobic isolates were susceptible at less than or equal to 100 microgram/ml and 85% by less than or equal to 25 microgram/ml of ticarcillin. Sixteen patients responded well to ticarcillin and two failed to respond. Our study suggests that ticarcillin is useful in the treatment of anaerobic infections.

Oral ciprofloxacin vs parenteral cefotaxime in the treatment of difficult skin and skin structure infections. A multicenter trial.

A prospective, randomized, double-blind, multicenter study was conducted of hospitalized patients to compare the efficacy and safety of oral ciprofloxacin (dosage, 750 mg every 12 hours) with intravenous cefotaxime (dosage, 2.0 g every 8 hours) as monotherapy for difficult skin and skin structure infections requiring hospitalization. Five hundred seventy patients were assessed for an analysis of safety and 461 patients were assessed for an analysis of efficacy. The most common infections were infected ulcers and abscesses. At the end of therapy, there was a higher incidence of recurrent or persistent organisms in the cefotaxime group compared with ciprofloxacin. Adverse reactions related to either therapy were rare. By pathogens, there were no differences in activity, except the higher rate of recurrent or persistent Pseudomonas aeruginosa infection in the cefotaxime group. By diagnosis, the two drugs had comparable efficacy, except for the higher incidence of bacteriologic failure in patients with polymicrobial infected ulcers in the cefotaxime group. Larger studies are needed to evaluate emergence of resistance to ciprofloxacin. Oral ciprofloxacin therapy is as safe and effective as parenteral cefotaxime in the treatment of difficult infections of the skin and skin structure, and affords the prospect of early discharge from the hospital and significant cost savings.

Spinal epidural abscess due to Actinomyces israelii.

A 31-year-old man had back pain, weight loss, fever, and paraplegia, with radiographic evidence of a left upper lobe lesion and lytic lesions in ribs and vertebral bodies. Gallium uptake was increased over the spine. At surgery we found a paraspinal abscess due to Actinomyces israelii. The patient responded to surgery and penicillin therapy. This is the first report of a case of actinomycotic spinal epidural abscess necessitating emergency surgery since the advent of penicillin.

In vitro activity and in vivo evaluation of ticarcillin plus clavulanic acid against aerobic and anaerobic bacteria.

The efficacy of ticarcillin plus clavulanic acid was compared with that of certain broad-spectrum antibiotics such as ticarcillin, azlocillin, and piperacillin against blood culture isolates of aerobic bacteria obtained from seriously ill patients and anaerobic bacteria obtained from other miscellaneous infections. Ticarcillin plus clavulanic acid was found to be as effective as other broad-spectrum antibiotics against most of the 285 septicemic isolates tested. Ticarcillin plus clavulanic acid was most effective against 351 anaerobic bacteria, including B. fragilis. Further, 32 strains of B. fragilis that were relatively resistant to ticarcillin and azlocillin were tested with a mixture of ticarcillin or azlocillin, each in combination with clavulanic acid. Ticarcillin plus clavulanic acid inhibited all 32 strains of B. fragilis. Addition of clavulanic acid to cephalothin, penicillin, or azlocillin also augmented the antibiotic activity against B. fragilis by 4- to 64-fold. These in vitro data suggest that ticarcillin plus clavulanic acid may be used as a single antibiotic in the cases of bacterial septicemias and that the combination may be used in the treatment of multiple-antibiotic-resistant bacterial strains. In a related study, the augmentation activity of clavulanic acid with penicillin or ticarcillin was evaluated against B. fragilis in a rat intra-abdominal abscess model. Gelatin capsules filled with a mixture of B. fragilis and Escherichia coli were implanted intraperitoneally in male Wistar rats. Four different groups of animals with appropriate controls were treated with penicillin or ticarcillin alone or in combination with clavulanic acid. Treatment was started immediately or delayed for 48 hours after peritoneal soilage. The mortality rate decreased by almost one half when antibiotic therapy was started immediately. Treatment with ticarcillin plus clavulanic acid resulted in a cure in 70 to 89 percent of animals, showing that this combination is the most effective regimen in the treatment of rats with experimental intra-abdominal abscesses caused by B. fragilis and E. coli.

Ticarcillin plus clavulanic acid versus moxalactam in the treatment of skin and soft tissue infections.

A formulation of 3.0 g of ticarcillin and 0.1 g of clavulanic acid was evaluated in the treatment of skin and soft tissue infections, and its efficacy was compared with that of moxalactam in a randomized open study. Thirty-three patients received 3.1 g of ticarcillin plus clavulanic acid every six hours via intravenous infusion, and 36 patients received 2.0 g of moxalactam every eight hours via intravenous infusion. Diagnostic categories included intramuscular abscesses, cellulitis, skin ulcers, gangrene, and perirectal abscesses. The average age of the patients and the duration of therapy were similar in both groups. Overall, 45 aerobic and 25 anaerobic bacteria were isolated from the ticarcillin plus clavulanic acid-treated patients; 58 aerobic and 24 anaerobic bacteria were isolated from the moxalactam-treated patients. Thirty of 33 patients in the ticarcillin plus clavulanic acid-treated group had a satisfactory response; a skin rash developed in one patient; therapy failed in one patient with Staphylococcus aureus infection; and one patient died as a result of a bleeding peptic ulcer. In the moxalactam-treated group, 32 of 36 patients had a satisfactory response; a skin rash developed in one patient; therapy failed in a patient with Pseudomonas aeruginosa infection; and two patients were unevaluable. Ticarcillin plus clavulanic acid as a single agent was found to be as effective as moxalactam in the treatment of skin and soft tissue infections.

Imaging endocarditis with Tc-99m-labeled antibody--an experimental study: concise communication.

The sensitivity and specificity of Tc-99m-labeled antibacterial antibody (Tc-99m Ab) for detecting bacterial endocarditis were evaluated in an experimental model. Rabbit-produced antistaphylococcal antibody was extracted using Rivanol and chemically labeled with Tc-99m. This Tc-99m Ab was injected intravenously in New Zealand rabbits 24 hr after producing Staphylococcus aureus endocarditis of the aortic valve. Imaging and tissue analyses were performed on the following day. All 11 animals developed S. aureus aortic-valve vegetations and showed increased uptake of Tc-99m Ab at the aortic valve, 118 times higher than at the uninfected tricuspid valve. Although high hepatic radioactivity and anatomic uncertainties interfered with in vivo delineation of these lesions, images of the excised hearts showed all affected valves. Two rabbits inoculated with Escherichia coli did not develop endocarditis and had little uptake of Tc-99m Ab, while six rabbits with enterococcal endocarditis had no uptake of the Tc-99m Ab in their vegetations. The findings suggest potential value of Tc-99m Ab on the rapid diagnosis of endocarditis.

Treatment of spontaneous bacterial empyema thoracis.

The need for decortication to cure primary bacterial (nontuberculous) empyema was evaluated in 112 consecutive patients. Twenty-eight patients (25%) were cured by thoracentesis alone. Intercostal chest tube drainage was required in 43 (39%) and decortication in 41 (36%). Although hospital stay was shortened by 5 days for those who had decortication, the difference was statistically insignificant. Penicillin failed to eradicate infection in nine of 17 patients, four of whom had Bacteroides organisms. There were no therapeutic failures among 46 patients treated with clindamycin and gentamicin. We conclude that conservative therapy, such as thoracentesis, antibiotics directed against anaerobic bacteria, and intercostal tube drainage (thoracostomy), was adequate to achieve clinical and physiologic resolution in about two thirds of all patients with primary bacterial empyema. The remaining one third required decortication. Rib resection and Eloesser flap procedures seem to be unnecessary in the treatment of primary bacterial empyema.

Rapid diagnosis of anaerobic empyema by direct gas-liquid chromatography of pleural fluid.

Sixty samples of pleural fluid from 52 patients were subjected to direct gas-liquid chromatographic studies, and results were correlated with findings from microbiologic cultures. Fourteen patients had anaerobic empyema, 22 had aerobic infections, and 16 had sterile pleural effusions. Multiple volatile fatty acids or succinic acid or both were found as markers of anaerobic infection in all but one instance. Aerobic infections and sterile pleural fluids were characterized by the absence of multiple volatile fatty acids or succinic acid. Infection with Bacteroides, when present, was characterized by a major product of succinic acid. One patient infected with Peptococcus magnus (which does not produce fatty acids or succinic acid) could not be diagnosed by gas-liquid chromatograms. Two patients without anaerobic bacteria in the pleural effusions but who had infections associated with Bacteroides fragilis outside the pleural space demonstrated succinic acid in the pleural fluid. With these exceptions, the presence of volatile fatty acids or succinic acid in pleural fluid was considered characteristic of anaerobic empyema. Direct gas-liquid chromatographic study of pleural fluids is, therefore, recommended as a routine procedure for rapid diagnosis of anaerobic empyema.

Hemoptysis in patients with septic pulmonary infarcts from tricuspid endocarditis.

Three drug addicts with tricuspid valve endocarditis and pulmonary cavitation secondary to septic pulmonary infarcts developed massive hemoptysis. Two patients died of asphyxia and one survived. Both who died were improving clinically and had negative blood cultures when the fatal hemoptysis occurred. Therefore, however slight it may be, hemoptysis occurring in association with septic pulmonary infarcts associated with endocarditis may require prompt and aggressive measures.

Antimicrobial activity of antituberculosis agents against anaerobic bacteria.

Anaerobic infections may coexist with tuberculosis, and can be mistaken for one another. The effect of therapy with antituberculosis chemotherapeutic agents against anaerobic bacteria (with the exception of rifampin) is unknown. We therefore examined the in vitro efficacy of certain commonly used antituberculosis agents (rifampin, isoniazid, and ethambutol) against 370 strains of anaerobic bacteria, including 86 isolates of Bacteroides fragilis. Rifampin at a concentration of 2 microgram/ml inhibited 91 percent of all anaerobic isolates. Both ethambutol and isoniazid were totally ineffective against any of the anaerobes tested, even at 64 microgram/ml. Therapy with rifampin in an unsuspected anaerobic infection can be misdiagnosed for tuberculosis. Therefore, when tuberculosis is suspected, isoniazid and ethambutol can be used and rifampin withheld until the acid-fast bacilli are demonstrated by additional diagnostic procedures, such as transtracheal aspiration.

Treatment of anaerobic pulmonary infections; carbenicillin compared to clindamycin and gentamicin.

Twenty-three patients with anaerobic infections of the lung were treated with either two antibiotics, clindamycin and gentamicin (11 patients) or with a single antibiotic, carbenicillin (12 patients). Cultures were obtained prior to therapy, either by transtracheal needle aspiration (17 patients) or thoracocentesis (six patients). Anaerobic bacteria were found in all. Fifteen patients had aerobic and facultative bacteria in addition. The anerobic isolates were peptostreptococci (12), peptococci (12), Bacteroides organisms (eight), clostridia (three), actinomycetes (two), eubacteria (one), and fusobacteria (one). Aerobes included streptococci (nine), enterococci (seven), Neisseria organisms (two), Klebsiella organisms (one), Citrobacter organisms (one), Pseudomonas organisms (one), Mycobacterium tuberculosis (two), and Nocardia (one). The two patients with pulmonary tuberculosis with anaerobic and superinfection received antituberculosis chemotherapy in addition. Therapeutic response was considered excellent in both groups. This suggests that carbenicillin may be used as a single antibiotic in the treatment of anaerobic and mixed infections of the lung.

Tissue levels of doxycycline in the human lung and pleura.

Antibiotic concentrations in the human lung and pleural tissue were measured following intravenous administration of doxycycline. The average serum levels were 9.3, 7.0 and 3.0 micrograms/ml at 1, 2, and 3 hours; correspondingly, the lung tissue levels were 6.8, 3.5 and 2.3 micrograms/g. The pleural tissue antibiotic concentrations at the same time intervals were 2.5, 1.5, and 1.5 micrograms/g. This suggests that doxycycline is retained well by the lung and the pleura, well above the minimal inhibitory concentration of most of the common bacterial pathogens of the lung, and may be used in the treatment of lung infections caused by susceptible organisms.

Pulmonary mycetoma due to Coccidioides immitis.

Pulmonary mycetoma due to Coccidioides immitis has been reported on three occasions. The present case is the fourth such report occurring in a patient with widely disseminated disease. Spherules and hyphae were found in the specimen. While the active pulmonary and extra-pulmonary lesions responded well to therapy with amphotericin B, resection was required to eliminate the residual mycetoma and its attendant hemoptysis.

Antimicrobial effect of amniotic fluid.

The antimicrobial effect of amniotic fluid (AF) obtained during the first (AF1) and second (AF2) trimesters was compared with the third (AF3) against anaerobic bacteria, such as Bacteroides fragilis ss. fragilis (6 strains), Eubacterium lentum (3 strains), and Peptostreptococcus anaerobius (4 strains). Escherichia coli (5 strains) served as a positive control. AF1 supported the growth of all 4 anaerobes (except B fragilis for 4 hours) for the entire 24-hour period tested. AF2 supported the growth of E coli and B fragilis for 24 hours but temporarily inhibited P anaerobius and E lentum. In contrast, AF3 inhibited all bacteria tested for 8 hours or more. It is concluded that AF1 is the least inhibitory, AF3 the most, and AF2 intermediate for the organisms tested. Lack of antimicrobial effect of AF on anaerobic bacteria may be one explanation for the higher incidence of anaerobic infections during absortion than during the prenatal period.

Ciprofloxacin monotherapy for acute pelvic infections: a comparison with clindamycin plus gentamicin.

This prospective, randomized controlled study compared the efficacy and safety of ciprofloxacin alone versus a conventional two-drug regimen, clindamycin with gentamicin. The study group included 71 patients hospitalized for pelvic infections such as acute (N = 33) and chronic (N = 8) salpingitis, tubo-ovarian abscesses (N = 11), endometritis (N = 9), septic abortion (N = 3), and other categories (N = 7). Twenty-two of 35 patients on ciprofloxacin and 20 of 36 on clindamycin plus gentamicin had culturable pathogens: gonococci in 28, anaerobes in six, chlamydia in four, and associated pathogens in 19. Complete clinical and bacteriologic cure was achieved in 21 of 22 (95%) in the ciprofloxacin group and 19 of 20 (95%) in the clindamycin plus gentamicin group. The mean duration of intravenous/oral ciprofloxacin therapy was 3.7/7.2 days, and it was 3/6.6 days for clindamycin plus gentamicin. Ciprofloxacin, a new quinolone, appears to be safe as a single-drug therapy and was as effective as the combination of clindamycin plus gentamicin for the treatment of severe pelvic infections requiring hospitalization.

Cefmenoxime therapy for gynecologic and obstetric infections.

Cefmenoxime, a new third-generation cephalosporin, was used as a single drug in the therapy for female genital tract infections. Therapeutic response was considered satisfactory in 21 of 22 cases of pelvic inflammatory disease, six of nine tuboovarian abscesses, two of three severe wound infections, and all five cases of endometritis. Overall, 34 of 39 patients responded. The peak serum antibiotic levels in this study ranged from 15.8 to 64 (average 48.7) micrograms/mL, and the trough level ranged from 0.9 to 4 (average 3.1) micrograms/mL. Cefmenoxime was tested in vitro against 424 isolates of anaerobes including 208 strains of bacteroides of which 80 were Bacteroides fragilis. Cefmenoxime inhibited the growth of 90% or greater of the organisms (minimal inhibitory concentration 90) at less than or equal to 64 micrograms/mL. The minimal inhibitory concentration for 75% of B fragilis was 32 micrograms/mL. This study suggests that cefmenoxime as a single-drug therapy is effective in the treatment of female genital tract infections caused by aerobic (including the gonococcus) and anaerobic bacteria.

Anatomic basis of head and neck infections.

The head is the portal for all infections acquired by ingestion and inhalation. The oropharynx, with its fine microbiologic niches around the teeth, serves as a source for endogenous pyogenic infections of the head and neck. The anatomic connections of the head with the mediastinum through extensions of the deep cervical fascia, and the intracranial venous sinuses connected through emissary veins to the facial veins, make infections of this region the most dreaded. Perhaps no other set of lymph nodes in the human body is challenged as frequently by microbiologic insults as the cervical lymph nodes.

Osteolytic lesion indicating Pseudomonas sternal osteomyelitis.

Two cases of osteolytic lesion of the sternum were caused by Pseudomonas aeruginosa. Both were in heroin addicts, and both occurred as a delayed reaction to injury in an automobile accident. Bony curettage and appropriate antibiotic therapy were sufficient for diagnosis and cure. Tobramycin sulfate (3 mg/kg/day), a new aminoglycoside, was successfully used in both instances. Excision of the sternum was not necessary.