Search

The in vitro activity of ceftriaxone was compared with those of other recently introduced beta-lactam antimicrobial agents (cefoperazone, cefotaxime, and moxalactam) and with those of cefoxitin, clindamycin, and metronidazole against 227 strains of anaerobic bacteria. The data obtained in this investigation suggest that ceftriaxone, like a majority of the new beta-lactam antimicrobial agents, may be of limited value in the treatment of serious infections involving anaerobic bacteria.

Intravenous metronidazole was administered, either by continuous or intermittent infusion, to 20 patients with infections involving anaerobic bacteria; 14 of the 20 patients were changed to oral administration of metronidazole for completion of therapy. Six of eight patients with infections derived from oropharyngeal bacterial flora were cured; the addition of ampicillin was required in one patient, however, because of an incomplete response to metronidazole. Eight of eleven evaluable patients with infections derived from bowel flora were also cured by metronidazole or metronidazole plus an aminoglycoside. Of 93 anaerobic bacteria isolated before therapy, 89 were susceptible to 16 micrograms or less of metronidazole per ml. Mean plasma levels of metronidazole were 27.6 +/- 11.4 micrograms/ml in patients receiving continuous infusions of drug and 19.9 +/- 10.7 micrograms/ml (trough) in patients receiving intermittent infusions. Two patients developed peripheral neuropathy during therapy. Metronidazole is an effective agent for the treatment of anaerobic infections. Because metronidazole is not active against facultative and aerobic bacteria, the addition of a second antimicrobial agent may be required for the treatment of mixed anaerobic-aerobic infections.

Amikacin was used to treat 7 serious gram-negative bacillary infections in patients undergoing chronic hemodialysis. 4 were caused by pathogens resistant to gentamicin. 5 infections were cured; 1 was improved and another failed to respond. Mean 1-hour peak serum levels of amikacin ranged from 25.8 to 44.3 microgram/ml. Mean serum levels of amikacin after 6 h of hemodialysis were 61.5% of predialysis levels. Amikacin is highly effective but doses must be reduced in patients requiring hemodialysis and serum levels monitored to avoid ototoxicity.

The in vitro activity of rosamicin was determined against 231 strains of anaerobic bacteria and compared with the activity of erythromycin against the same strains. Rosamicin and erythromycin had similar activity against strains of Peptostreptococcus and gram-positive nonsporeforming bacilli. Rosamicin was somewhat more active against strains of Peptococcus, Clostridium, and gram-negative anaerobes. All strains of Bacteroides fragilis tested were inhibited by 4 mug of rosamicin or less per ml, whereas only 76% of them were inhibited by this concentration of erythromycin. Rosamicin was distinctly more active against Fusobacterium nucleatum. Because of its in vitro activity, further investigation of the pharmacology of this drug is warranted.

Anaerobic bacteria are commonly involved in a number of common infections--especially aspiration pneumonia, intraabdominal infection, and a variety of female genital tract infections. Certain distinctive clinical features suggest the possibility of anaerobic infection; included are foul odor, infection in proximity to a mucosal surface, abscess formation, and gas in tissues or discharges. Treatment includes surgical management (debridement and drainage) and use of appropriate antimicrobial agents.

A susceptibility survey of 537 strains of the Bacteroides fragilis group from eight centers in the United States was continued at the Tufts New England Medical Center in 1982. The results were compared with those of 755 organisms analyzed in 1981. Nine antimicrobial agents were tested by an agar dilution method. The respective percentages of resistance for 1981 and 1982 were as follows (%): cefoxitin, 8 and 10; moxalactam, 22 and 12; cefotaxime, 54 and 48; cefoperazone, 57 and 54; piperacillin, 12 and 7; clindamycin, 6 and 3; metronidazole, 0 and 0; chloramphenicol, 0 and 0; and tetracycline, 63 and 59. Regional differences in resistance rates were found. Declines in resistance to moxalactam, piperacillin, and clindamycin were noted at the participating hospitals. An outbreak of cefoxitin resistance was noted at the Tufts New England Medical Center, where the rate increased from 14 to 30%. The various species of the B. fragilis group had differing patterns of resistance; B. fragilis was the most susceptible species. Significant cross resistance among the beta-lactam agents was found. These data indicate the need to determine the susceptibility patterns of the B. fragilis group organisms within each hospital.

Anaerobic bacteria currently demonstrate increased resistance to antimicrobial agents, primarily by the production of beta-lactamase. A number of species of Bacteroides, most notably those in the Bacteroides fragilis group, produce these enzymes. A few species of Fusobacterium and Clostridium produce beta-lactamase as well. Fortunately, this mechanism of resistance is readily overcome by administering beta-lactamase inhibitors coupled with a beta-lactam antibiotic that would otherwise be inactivated. Other types of resistance encountered in anaerobic bacteria include inactivating enzymes such as chloramphenicol acetyltransferase, plasmid-mediated transferable multiple-drug resistance, changes in porin molecules in the outer membrane of the bacterial cell, decreased uptake of drug by other mechanisms, changes in the target organs such as penicillin-binding proteins, and decreased reduction of the antibiotic to an active intermediate product. In many institutions, certain drugs such as cefoxitin, clindamycin, and piperacillin, which were previously active against almost all strains of B. fragilis, are now effective against only 70 to 85% of this group of anaerobes. Drugs with essentially 100% activity against most anaerobic bacteria include chloramphenicol, imipenem, metronidazole, and the combinations of a beta-lactam antibiotic plus a beta-lactamase inhibitor such as ampicillin plus sulbactam and amoxicillin or ticarcillin combined with sodium clavulanate. This paper also discusses the indications for antimicrobial susceptibility testing of anaerobes as well as problems encountered with testing techniques that are currently being used.

Legionella pneumophila infections frequently manifest themselves as a multisystem disease with acute pneumonia. Certain clinical and laboratory features are helpful in diagnosis but none are pathognomonic. Diagnosis frequently must be made clinically and erythromycin given presumptively because of the delay in seroconversion but culture and direct fluorescent antibody testing are quite useful for rapid diagnosis. Epidemiologic and laboratory investigations will undoubtedly yield considerable information about this fascinating bacterial disease.

To evaluate the effects of parenteral cefoxitin therapy on human fecal flora, we cultured fecal specimens obtained from six patients before, during, and after therapy and used standard methods to identify and quantify all microorganisms. The major changes (observed in at least three patients) included the acquisition or proliferation of group D Streptococcus species, coagulase-negative Staphylococcus species, cefoxitin-resistant members of the family Enterobacteriaceae, Pseudomonas species, and various species of the Bacteroides fragilis group. The most striking finding was ingrowth of Clostridium difficile, noted in five of the six patients. There was concomitant eradication or decrease of cefoxitin-susceptible Enterobacteriaceae family members, Bacteroides species other than the B. fragilis group, Clostridium species other than C. difficile, and Lactobacillus species. These marked alterations of fecal flora may have important clinical consequences.

Anaerobic bacteria often are neglected in discussions of the bacteriology of mediastinitis. Two cases of anaerobic mediastinitis are reported and the literature in this field is reviewed. Anaerobes are important pathogens in the etiology of mediastinitis secondary to perforation of the esophagus, extension of a retropharyngeal abscess, or extension of cellulitis or abscess of dental origin from the neck. Although anaerobes indigenous to the oral cavity predominate in these cases, there are also a few cases reported involving Bacteroides fragilis. The source of the mediastinitis should be considered when antimicrobial therapy is initiated so that appropriate anaerobic coverage can be included when indicated.

We characterized clinical isolates previously identified in our laboratory as Bacteroides ruminicola, the human strains of which are now classified as Bacteroides oris and Bacteroides buccae. A total of 72 isolates (55 B. buccae isolates and 17 B. oris isolates) recovered over a 10-year period were studied. They were differentiated from each other by special-potency antibiotic disks and the RapID-ANA system. The two organisms were associated with a variety of infections, the majority being pleuropulmonary (29.2%) and infections of the head and neck region (27.8%). The infections were always polymicrobial, usually with more than five organisms per specimen. A total of 44% of the B. oris strains and 27% of the B. buccae strains were resistant to penicillin G (breakpoint, 2 U/ml), and this correlated with the presence of beta-lactamase. Although B. oris and B. buccae are found with some frequency in human infections, they are present primarily as components of a mixed flora.

Clostridium difficile has been shown to be a cause of antimicrobial agent-associated diarrhea and colitis. The source from which this organism gains access to the gastrointestinal tract is not known. Cultures of the hospital environments of six of eight patients whose fecal cultures were positive for C. difficile yielded this organism, whereas cultures of control hospital sites were almost invariably negative. These data suggest that hospital environmental contamination may be a potential source of infection. Further studies are needed to determine the role of various possible sources of C. difficile in human diarrheal disease.

Strongly catalase-positive Gram-negative anaerobic rods were isolated from approximately half of all intra-abdominal specimens received from patients with gangrenous and perforated appendicitis, and subsequently also from normal faecal specimens. The organism was originally detected on Bacteroides-bile-aesculin (BBE) agar, and grew slowly on non-selective anaerobic media containing blood. It was stimulated by bile and differed from other known genera by being urease- and catalase-positive, and by reducing nitrate. It did not reduce sulphate. Other anaerobic Gram-negative rods showed no homology by DNA dot-blot hybridization. The thermal melting profile of chromosomal DNA showed 39-40 mol% G + C. The whole-cell fatty acid methyl ester profile included cyclic and branched long-chain acids, and differed from those of all other anaerobes that have been tested. beta-Lactamase was not detected. The name Bilophila wadsworthia gen. nov., sp. nov. is proposed for this organism.

Tympanocentesis was performed in 50 patients with chronic otitis media; pus was cultured aerobically and anaerobically. Only aerobes were isolated from 21 patients (42%), three patients had only anaerobes (Peptococcus sp), and 25 patients (50%) had both aerobes and anaerobes. Only one specimen had no growth. There were 68 aerobic isolates. Pseudomonas aeruginosa was recovered in 36 patients (72%); other aerobes commonly recovered included Proteus sp and Staphylococcus aureus. There were 48 anaerobes isolated. Anaerobic Gram-positive cocci were isolated in 24 instances (21 Peptococcus sp and three Peptostreptococcus sp). Sixteen Bacteroides sp were recovered, including seven B fragilis group and six B melaninogenicus.

Almost all cases of Clostridium difficile-related pseudomembranous colitis are related to antimicrobial therapy. Virtually all antibacterial agents have been implicated, notable exceptions being vancomycin and parenterally administered aminoglycosides. The most prominent causes of colitis are ampicillin, clindamycin and various cephalosporins. In general, this complication is related to suppression of indigenous flora and overgrowth of C. difficile. In the case of ampicillin, however, C. difficile is always susceptible. Beta-lactamase production by elements of the bowel flora leads to destruction of ampicillin and subsequently to increased counts of C. difficile and colitis. Much less well-appreciated, and much less studied, is overgrowth and subsequent infection by other types of anaerobic bacteria. Superinfection by anaerobes may follow the use of "intestinal antiseptics" such as oral neomycin; indeed, that is the rationale for the current practice in the U.S. of combining erythromycin or tetracycline with the oral aminoglycoside. Superinfection with anaerobes may also follow systemic administration of various antimicrobial compounds. Such superinfections may involve any site in the body, although sepsis and intraabdominal infection have been noted most commonly; all major types of anaerobes have been involved. A wide variety of antimicrobial compounds has been implicated in predisposing to anaerobic infection.

Many manifestations following jejunoileal bypass are due to chronic inflammation of the excluded bowel rather than short bowel malabsorption. Diarrhea, abdominal distention, and gas-fluid levels were common diagnostic features of "bypass enteropathy." Exploration showed the bypassed bowel to be dilated, with serosal inflammation and pneumatosis cystoides intestinalis. The bypassed loops contained a fecal flora and the mucosa demonstrated nonspecific chronic inflammatory changes. Exudative protein losses were noted. Systemic complications of bypass enteropathy were similar to other inflammatory diseases of the bowel. Improvement following treatment with metronidazole or after dismantling of the bypass suggested that bacterial byproducts originating in the excluded bowel were causally related.

The susceptibility of 49 strains of Clostridium ramosum to 10 antibiotics was determined by agar dilution and disk diffusion tests. Results showed that, among the anaerobes, C. ramosum is second only to Bacteroides fragilis in its resistance to antimicrobial agents. All strains were susceptible to penicillin, carbenicillin, chloramphenicol, vancomycin, and metronidazole at readily achievable blood levels. Most strains (83%) were susceptible to erythromycin. There was a high level of resistance to clindamycin in 16% of the strains. All isolates were resistant to rifampin and gentamicin, and most were resistant to lincomycin. Assessment of susceptibility by measurement of inhibition zone diameters with disk diffusion tests was not satisfactory.

Leptotrichia buccalis is an obligately anaerobic, gram-negative rod classified as a member of the family Bacteroidaceae. Organisms found in this family (Bacteroides and Fusobacteria) are frequent causes of severe infection in human beings. L. buccalis is a constituent of normal oral flora. Leptotrichia has rarely been recovered from mixed infections primarily of the head and neck. It has not previously been reported as a cause of serious infection in man. We report a case of cavitary pneumonia and septicemia caused by L. buccalis. The colonial morphology and gram stain of L. buccalis are characteristic. Definitive identification is made by gas-liquid chromatography. Leptotrichia have been shown to contain potent endotoxin. L. buccalis has the potential to be a virulent, pathogenic microorganism, especially in the compromised host.

In a double-blind, randomized, controlled trial, 249 patients with complicated urinary tract infections received either 400 mg. enoxacin or 160 mg. trimethoprim plus 800 mg. sulfamethoxazole orally every 12 hours for 14 days. The clinical outcome at the end of treatment revealed that all 89 evaluable patients (100 per cent) in the enoxacin group and 88 of 90 (98 per cent) in the trimethoprim-sulfamethoxazole group had satisfactory clinical responses (cure or improvement). Bacteriological effectiveness was measured cumulatively based on responses during and at the end of treatment, and 7 days later at followup. Satisfactory bacteriological responses (eradication or superinfection at all evaluations throughout the study) were achieved in significantly more (p equals 0.03) patients treated with enoxacin (93 per cent) than in those treated with trimethoprim-sulfamethoxazole (83 per cent). Both study medications were well tolerated. These results indicate that oral enoxacin was more effective clinically and bacteriologically (the latter statistically so) than trimethoprim-sulfamethoxazole when given as empiric therapy in the treatment of complicated urinary tract infections.

The antimicrobial susceptibility of 492 anaerobic bacteria, the majority of which were recent clinical isolates, was determined by the agar dilution technique. Penicillin G was active against most of the strains tested at 32 U or less/ml, but only 72% of Bacteroides fragilis strains were susceptible at this level and 9% required 256 U or more/ml. Ampicillin was effective against most of the strains except B. fragilis at 16 mug or less/ml. Amoxicillin was active against only 31% of B. fragilis, 76% of other Bacteroides species, and 67% of Fusobacterium species at 8 mug/ml. Two new penicillins, mezlocillin and azlocillin, were similar to ampicillin in their activity. Carbenicillin and ticarcillin inhibited all but a few strains at 128 mug or less/ml. BLP 1654 was somewhat more active than penicillin G against B. fragilis but had similar activity against other anaerobes. Cephalothin was inactive against B. fragilis, and only 65% of other Bacteroides species were inhibited by 32 mug or less/ml. It was effective against all other anaerobes at that level. Cefamandole showed somewhat greater activity than cephalothin against B. fragilis but generally less activity against gram-positive organisms. Cefazaflur (SKF 59962) was comparable to cephalothin against B. fragilis. Cefoxitin was distinctly more active than cephalothin against B. fragilis. These latter two agents were less active than cephalothin against the gram-positive anaerobes. Chloramphenicol remains active against anaerobic bacteria at 16 mug or less/ml, with rare exceptions. Thiamphenicol was similar to chloramphenicol in its activity. Clindamycin was very active against most of the anaerobes at 8 mug or less/ml. Erythromycin and josamycin were also tested, with josamycin showing greater activity against B. fragilis than either erythromycin or clindamycin. A new oligosaccharide, everninomicin B, was less active than clindamycin against B. fragilis but more active against clostridia and some of the other strains tested. Most of the groups of bacteria tested demonstrated a trend toward resistance to tetracycline. Doxycycline and minocycline were somewhat more active than was tetracycline. Metronidazole was active against the majority of the anaerobes tested; resistance ws demonstrated by some of the gram-positive cocci and gram-positive, non-sporeforming bacilli.

The minimal inhibitory concentrations of nine antimicrobial agents was determined for over 750 clinical isolates of the Bacteroides fragilis group of anaerobic bacteria collected from nine centers in the United States during 1981. High resistance rates were documented for cefoperazone, cefotaxime, and tetracycline. Cefoxitin had the best activity of the beta-lactam antibiotics, whereas moxalactam and piperacillin had good activities. The resistance rate for clindamycin was 6%. There were no metronidazole- or chloramphenicol-resistant isolates encountered. There were significant differences in susceptibility among the various species of the B. fragilis group, particularly with moxalactam, cefoxitin, and clindamycin. Clustering of clindamycin-, piperacillin-, and cefoxitin-resistant isolates was observed at different hospitals. The variability of resistance rates with the beta-lactam antibiotics and clindamycin indicates that susceptibility testing of significant clinical isolates should be performed to define local resistance patterns.

Twenty patients undergoing urgent or emergency surgical procedures where intra-abdominal infection was suspected were treated with doxycycline hyclate. Wound infections involving anaerobic, aerobic, or facultative bacteria developed in four of 11 patients treated with doxycycline alone. Nine other patients received higher doses of doxycycline plus gentamicin sulfate. Five of these had postoperative infections primarily involving anaerobic organisms. Bacteremia with a doxycycline-resistant Bacteroides fragilis developed in one patient during therapy. Serum levels of doxycycline, even at the higher dosage, were below the minimal inhibitory concentrations (MICs) of a number of potential pathogens isolated at the time of surgery. Doxycycline is not indicated in cases of serious intra-abdominal infection unless the infecting flora are known to be susceptible.

The contents of the proximal jejunum and distal ileum were cultured quantitatively in eight patients who were undergoing intestinal bypass procedure for obesity. Five jejunal specimens were sterile, and three contained low counts of a predominantly aerobic flora. Ileal contents yielded variable but usually higher counts than in the jejunum, and there were similar numbers of anaerobes and aerobes. In three patients in whom a bypass was established, contents of the functioning small bowel showed counts of 10(5.0)-10(7.6) colony-forming units/ml. These counts exceeded the counts in the normal terminal ileum, and the flora qualitatively resembled that of feces. Four specimens from excluded loops revealed colonization with fecal organisms, and the counts ranged between 10(6.4) and 10(9.7) colony-forming units/ml. In jejunoileal bypass both the functioning small bowel and the excluded loop become colonized with colonic flora, a phenomenon that may contribute to some of the side effects of this procedure.

The in vitro activity of imipenem, metronidazole, clindamycin, moxalactam, and cefoxitin against 203 strains of anaerobic bacteria isolated from patients at the Veterans Administration Wadsworth Medical Center in Los Angeles was studied. Imipenem and metronidazole were the most active agents overall, inhibiting 98% and 99%, respectively, of all anaerobes tested. At breakpoint levels all of the agents tested were very active against anaerobic cocci. Clostridium perfringens, and Bacteroides species other than those of the Bacteroides fragilis group. Imipenem, metronidazole, and clindamycin were the most active agents against the B. fragilis group in this study, although more recent experience with clindamycin indicates less potency. Marked variation among the susceptibility results obtained at various centers may be due to differences in technique, including inoculum size, media, and incubation time. In all instances, however, imipenem has clearly been the most active of the beta-lactam agents.

The etiologic agents usually involved in wound infections due to human or animal bites are the aerobic skin flora of the victim, e.g., Staphylococcus aureus, and/or the aerobic oral flora of the biter, e.g., Pasteurella multocida. While anaerobic bacteria are predominant in the normal oral flora of humans and animals, their importance in the pathogenesis of bite-wound infections has not been stressed. Most investigators in this field have either not cultured these wounds for anaerobic bacteria or not utilized optimal culture techniques. In a series of studies on human and animal bite wounds, methods that are optimal for recovery of anaerobic bacteria were used. Anaerobes were found in significant quantities in 39% of animal bite wounds, 50% of human bite wounds, and 56% of clenched-fist injuries. Several species of anaerobes usually were present in the wounds and always were present in mixed culture with aerobic oral flora. The anaerobes most commonly isolated included Bacteroides asaccharolyticus, Bacteroides bivius, Bacteroides disiens, Bacteroides melaninogenicus, Bacteroides oralis, Bacteroides ruminicola, Bacteroides pneumosintes, Bacteroides ureolyticus, Fusobacterium nucleatum, Fusobacterium russii, Peptococcus species, Peptostreptococcus species, and Veillonella species. Initial, empiric antimicrobial therapy for bite wounds should be directed against potential anaerobic as well as aerobic pathogens.

Gas liquid chromatography was performed on synovial fluid of 94 patients with exudative arthritis. A relatively constant pattern of peaks was obtained in all synovial fluid samples. Lactic acid was increased in synovial fluid of patients with septic arthritis excluding gonococcal arthritis. In addition 2 constant peaks with retention time of 546 and 848 seconds in the chromatogram usually showed a significant increase in the synovial fluids of patients with septic arthritis (including gonococcal arthritis) but not in those from patients with sterile inflammatory or degenerative arthritis. In 1 patient with pseudomonas arthritis an increase in the peaks was noted with clinical and bacteriological relapse and subsequently there was a gradual return to normal levels during clinical improvement. Increase in synovial fluid lactic acid is useful in the diagnosis of septic arthritis. Identification of the compounds represented by the 2 peaks, which presumptively correspond to n-valeric and n-hexanoic acid, may provide further information on diagnosis, prognosis and pathogenesis of arthritis and may help in the differentiation between gonococcal and nongonococcal arthritis.

The diagnosis of Branhamella catarrhalis pneumonia in five cases was established by culture of pulmonary secretions obtained by transtracheal aspiration. B catarrhalis caused an acute lobar pneumonia which usually responded promptly to appropriate antimicrobial therapy. Recognition that this organism may cause pneumonia in a nonimmunocompromised person should alert clinicians to consider it as a possible pathogen when Gramnegative diplococci are seen on smears of specimens from the lower respiratory tract.

Fusobacterium egg yolk agar is a new medium selective for Fusobacterium species and differential for Fusobacterium necrophorum. The medium is a Brucella Agar base (Difco Laboratories, Detroit, Mich.) containing vancomycin, neomycin, josamycin, and egg yolk. All species of fusobacteria grew with only minimal inhibition. The mean log difference in counts between Fusobacterium egg yolk agar and control media for 30 strains of seven species of fusobacteria was 0.1922. F. necrophorum typically showed a strong lipase reaction. Most other organisms were significantly inhibited by the medium.

Thirty patients received penicillin (17 of these also received dicloxacillin) and 31 received amoxicillin/clavulanic acid in a randomized study of the outpatient management of bite wounds. A wide variety of aerobic (185 strains) and anaerobic (47 strains) bacteria were isolated from these wounds. The control and study regimens were equally effective. There were four therapeutic failures in all. Aggressive wound management along with antimicrobial therapy led to a 87-96% cure rate. Loose stools or diarrhea was a more frequent side effect with amoxicillin/clavulanic acid than with penicillin +/- dicloxacillin.

Eikenella corrodens is a gram-negative rod that has been identified as a cause of endocarditis, osteomyelitis, pneumonia, cellulitis, and other infections. Because it is difficult to grow unless it is incubated in 10% carbon dioxide and because it may be overgrown by other organisms, it can be overlooked as a sinus pathogen. This is a report of the isolation of E corrodens from the sinuses of three patients with sinusitis. Three important features of infection with E corrodens, which are illustrated by these cases, are as follows: (1) the indolence of E corrodens infections; (2) the unusual susceptibility pattern of E corrodens; and (3) the fact that E corrodens is often isolated in mixed culture. The purulent contents of sinus cavities should be cultured in aerobic, anaerobic, and 10% carbon dioxide atmospheres.

Amikacin was administered to 18 patients with gram-negative septicemia. Ten of the patients had blood culture isolates highly resistant to gentamicin; six of these patients had persistent bacteremia while receiving gentamicin alone or in combination with other agents. Fourteen of the 18 patients were cured with amikacin therapy and adjunctive measures. Nine of the 10 patients with gentamicin-resistant pathogens were cured. The occurrence of nephrotoxicity in four patients with elevated amikacin serum levels and serious underlying disease indicates the desirability of monitoring serum amikacin levels. Minor ototoxicity occurred in two patients and was associated with prolonged therapy and high serum amikacin levels. Amikacin is a highly effective agent for treating patients with gram-negative bacteremia; it is the agent of choice in the therapy of patients with suspected or documented gram-negative bacteremia caused by pathogens resistant to gentamicin and susceptible to amikacin.

The efficacy and safety of ticarcillin plus clavulanic acid in the treatment of patients with infections of soft tissue, bone, and joint were evaluated in this open study. Clinical diagnoses included osteomyelitis, soft tissue abscess or ulcer, cellulitis, bite wound, traumatic or postoperative cellulitis, necrotizing fasciitis, septic arthritis, septic bursitis, and septic thrombophlebitis. Trauma or underlying disease such as diabetes mellitus or vascular insufficiency was common (more than 50 percent) in the patient population. Clinical efficacy was evaluable in 66 patients who received 3 g of ticarcillin and 0.1 g of clavulanic acid every four or six hours for a mean of 23.4 days. A satisfactory clinical response was observed in 92 percent of the patients. Major pathogens isolated were Enterobacteriaceae, anaerobic cocci, Staphylococcus aureus, and beta-hemolytic Streptococcus. Of the 143 isolates recovered from 55 bacteriologically evaluable cases, 87 percent were eradicated by therapy. Overall, a satisfactory bacteriologic outcome occurred in 93 percent of the patients, and the pathogen(s) persisted in 7 percent. More than 98 percent of the isolates were susceptible to ticarcillin plus clavulanic acid in vitro. Emergence of resistance during therapy occurred with three strains of Pseudomonas aeruginosa. Adverse drug-related reactions required discontinuation of treatment in two patients, although other minor abnormal laboratory findings were common. These results indicate that ticarcillin plus clavulanic acid offers safe and effective therapy for infections of soft tissue, bone, and joint.

The results of treatment of 10 patients with anaerobic infections with metronidazole are presented. Six patients were cured, three showed initial good response but circumstances required a change to another drug, and one patient did not respond. The unique spectrum of the drug, its pharmacology, and limitations are discussed. The results indicate that further clinical trials to determine the efficacy of metronidazole in the treatment of anerobic infections are indicated.

A simple, relatively rapid silver impregnation stain has been found to stain Legionella pneumophila effectively in paraffin-embedded tissue sections while permitting visualization of histological detail. It may also be used to stain the organism in body fluids. The stain is not specific and thus must be confirmed by direct fluorescent-antibody technique or culture, but, in the absence of other bacilli demonstrable by Gram or other stain, visualization of typical bacillary forms in a patient with illness compatible with Legionnaires disease provides strong presumptive evidence supporting this diagnosis.

The Analytab Products, Inc. (API), anaerobic multitest microsystem (MICRO) was compared with the Center for Disease Control conventional (CONV) thioglycolate (supplemented with hemin and vitamin K1) system and with pre-reduced anaerobically sterilized (PRAS) media as recommended by the Virginia Polytechnic Institute. Growth from a solid medium was suspended to produce standard inocula. Substrates included 16 carbohydrates, indole, urea, gelatin, and esculin. API strips were inoculated in air and incubated in GasPak (BBL) jars. MICRO tests were read at 1 and 2 days. CONV tests at 1, 2, and 7 days, and PRAS tests at 3 weeks. One hundred thirty well-characterized strains of anaerobes (76 gram-negative rods, 16 cocci, 26 gram-positive nonsporeforming rods, and 12 clostridia), including 48 reference strains, were studied. Of 2,600 tests performed, 2,085 (80.2%) showed agreement with all three methods. There was 90.9% agreement between the MICRO and CONV, 84.9% between the MICRO and PRAS, and 84.6% between the CONV and PRAS tests. All MICRO tests were reliable except for indole, which was not sensitive enough, and gelatin, which was very insensitive. The MICRO system permits performance of biochemical tests at the workbench in the average clinical laboratory without the need for expensive equipment and time-consuming procedures.

Antimicrobial activity of cefoxitin, cefotetan, cefotaxime, ceftizoxime, ceftazidime, imipenem, and clindamycin against four inocula of Bacteroides fragilis strains was determined on three different media. The inoculum sizes were 10(4), 10(5), 10(6), and 10(7) colony forming units (CFU) per spot. On all three media, substantial effects of inoculum size on minimal inhibitory concentrations (MIC) of cefotaxime and ceftizoxime were found: the doubled dilution differences in MICs between inocula of 10(7) and 10(4) CFU/spot were 2.2, 2.3, and 2.1 micrograms/ml of cefotaxime and 1.8, 4.4, and 4.0 micrograms/ml of ceftizoxime on Brucella base-laked blood agar, Wilkins-Chalgren agar, and a brain-heart infusion medium, respectively. An inoculum difference found on all three media with ceftazidime may also be of practical significance. There was evidence of larger differences between inocula on the Wilkins-Chalgren agar and brain-heart infusion than on the Brucella agar.