Approval of zidovudine (AZT) for acquired immunodeficiency syndrome. A challenge to the medical and pharmaceutical communities.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
I Brook
Publications and source records attributed to I Brook.
Microbiology of retropharyngeal abscesses in children.
Aspiration of retropharyngeal abscesses was performed in 14 children. Cultures were taken from aspirates for aerobic and anaerobic bacteria, and all yielded bacterial growth. Anaerobes were isolated in all patients; they were the only organisms isolated in two patients (14%) and were mixed with aerobes in 12 patients (86%). There were 78 anaerobic isolates (5.6 per specimen). The predominant anaerobes were Bacteroides species, Peptostreptococcus species, and Fusobacterium species. There were 26 aerobic isolates (1.9 per specimen). The predominant aerobes were alpha- and gamma-hemolytic streptococci, Staphylococcus aureus, Haemophilus species, and group A beta-hemolytic streptococci. beta-Lactamase production was noted in 16 isolates recovered from ten patients (71%). These included all isolates of S aureus, six of 18 Bacteroides melaninogenicus group (33%), and two of three Bacteroides oralis (67%). These findings demonstrate the major role of anaerobic organisms in retropharyngeal abscesses and the presence of beta-lactamase-producing organisms in two thirds of the patients.
Abscess↗
Microbiology of intra-abdominal abscesses in children.
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Abdomen↗
Glucan: mechanisms involved in its "radioprotective" effect.
It has generally been accepted that most biologically derived agents that are radioprotective in the hemopoietic-syndrome dose range (eg, endotoxin, Bacillus Calmette Guerin, Corynebacterium parvum, etc) exert their beneficial properties by enhancing hemopoietic recovery and hence, by regenerating the host's ability to resist life-threatening opportunistic infections. However, using glucan as a hemopoietic stimulant/radioprotectant, we have demonstrated that host resistance to opportunistic infection is enhanced in these mice even prior to the detection of significant hemopoietic regeneration. This early enhanced resistance to microbial invasion in glucan-treated irradiated mice could be correlated with enhanced and/or prolonged macrophage (but not granulocyte) function. These results suggest that early after irradiation glucan may mediate its radioprotection by enhancing resistance to microbial invasion via mechanisms not necessarily predicated on hemopoietic recovery. In addition, preliminary evidence suggests that glucan can also function as an effective free-radical scavenger. Because macrophages have been shown to selectively phagocytize and sequester glucan, the possibility that these specific cells may be protected by virtue of glucan's scavenging ability is also suggested.
5'-Nucleotidase↗
Bacterial synergy in pelvic inflammatory disease.
Polymicrobial aerobic and anaerobic flora are responsible for pelvic inflammatory disease (PID). The most frequent pathogens appear to be Neisseria gonorrhoea and anaerobic bacteria (most commonly anaerobic cocci and Bacteroides sp.). Recent studies have demonstrated the recovery of Chlamydia trachomatis in up to a third of these infections. Although N. gonorrhoea is frequently recovered from cervical cultures, it is less commonly recovered from intra-abdominal sites. Recent studies have demonstrated the in-vivo synergistic relationship between N. gonorrhoeae and Bacteroides fragilis. The growth of each component of the mixed infection was enhanced when these were present together in an abscess. Furthermore, the emergence of encapsulated strains was enhanced in these infections. This synergy enables the organisms to cause more severe local and systemic damage to the host. Therapeutic intervention should include the use of antimicrobial agents effective against both the aerobic and anaerobic components of the mixed infection. Unless such therapy is given, the infection may persist. It is also recommended to use antimicrobials that possess synergy between them against the bacterial pathogens. Agents effective against the anaerobic pathogens are metronidazole, clindamycin and cefoxitin. Antimicrobials effective against the Gram-positive aerobic pathogens and N. gonorrhoeae are spiramycin and penicillins. Aminoglycosides or third generation cephalosporins are effective against Gram-negative enterics. The combination of metronidazole and spiramycin has shown to be synergistic against mixed infections of Bacteroides sp. and N. gonorrhoeae.
Bacteria↗
Controversies in anaerobic infections in childhood.
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Anti-Bacterial Agents↗
Metronidazole and spiramycin in abscesses caused by Bacteroides spp. and Staphylococcus aureus in mice.
The activity of metronidazole and spiramycin, singly or in combination, was tested in vitro and also in vivo, in the eradication of infection caused by Bacteroides spp. and Staphylococcus aureus, alone or in combination. The MICs of metronidazole for the B. melaninogenicus and B. fragilis strains were significantly reduced by the addition of spiramycin (from 0.25 and 0.5 mg/l, to 0.062 and 0.125 mg/l, respectively). Antimicrobial synergy between metronidazole and spiramycin was noted against Bacteroides spp. in abscesses caused in mice by subcutaneous injection of Bacteroides spp. alone or in combination with S. aureus. Furthermore, an additional reduction in the number of S. aureus was noted in mixed infections with bacteroides that were treated with metronidazole alone. The antimicrobial synergy in vitro and in vivo between metronidazole and spiramycin may have clinical implications that deserve to be further investigated.
Abscess↗
Microbiology of human and animal bite wounds in children.
Aspirates from bite wounds in 39 children (21 with animal bites and 18 with human bites) were cultured for aerobic and anaerobic bacteria. Aerobic bacteria only were recovered in 7 (18%) wounds, anaerobic bacteria only in 3 (8%) and mixed aerobic and anaerobic bacteria in 29 (74%). A total of 59 isolates was recovered from animal bites (2.8/specimen): 37 aerobes (1.8/specimen); and 22 anaerobes (1.0/specimen). A total of 97 isolates were recovered from human bites (5.4/specimen): 44 aerobes (2.4/specimen); and 53 anaerobes (3.0/specimen). The most frequent isolates in both types of wounds were Staphylococcus aureus, anaerobic cocci and Bacteroides spp. Present only in animal bites were Pasteurella multocida, Pseudomonas fluorescens and M-5. Present only in human bites were Group A streptococci. Eighteen beta-lactamase-producing organisms were isolated in 16 wounds. This study demonstrates the polymicrobial aerobic-anaerobic nature of human and animal bite wounds.
Adolescent↗
Pathogenicity and therapy of anaerobic bacteria in upper respiratory tract infections.
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Bacteria, Anaerobic↗
Role of anaerobic beta-lactamase-producing bacteria in upper respiratory tract infections.
Bacteroides sp. (Bacteroides melaninogenicus, Bacteroides oralis and Bacteroides fragilis), peptostreptococci and Fusobacterium sp. are important pathogens in upper respiratory tract infections. A recent increase in numbers of beta-lactamase-producing strains of anaerobic Gram-negative bacteria in upper respiratory tract infections has been associated with increased failure rates of penicillins in eradication of these infections. These infections include chronic otitis media, chronic sinusitis and mastoiditis, chronic recurrent tonsillitis and lung abscesses. The indirect pathogenicity of these organisms is apparent through their ability not only to survive penicillin therapy but also to protect penicillin-susceptible pathogens from the drug. These direct and indirect virulence characteristics of anaerobic bacteria require the administration of appropriate antimicrobial therapy directed against all pathogens in mixed infections.
Bacteroides↗
Synergistic combinations of antimicrobial agents against anaerobic bacteria.
Studies evaluating the in vitro and in vivo synergistic potential of combined antimicrobial agents against anaerobic bacteria are reviewed. Most studies evaluated therapy against Bacteroides sp. (mostly Bacteroides fragilis group). The combinations found to be most effective against B. fragilis were between metronidazole and clindamycin, spiramycin or gentamicin and between clindamycin and aminoglycosides. Against Bacteroides melaninogenicus the effective combinations were penicillin or clindamycin plus gentamicin and metronidazole and spiramycin or gentamicin. Occasional synergy was observed against Clostridium sp. and anaerobic cocci with clindamycin and gentamicin. Synergistic combinations have the potential of clinical use in serious anaerobic infections.
Animals↗
Bacteraemia and seeding of capsulate Bacteroides spp. and anaerobic cocci.
The effect of capsulation on the ability of Bacteroides fragilis, B. asaccharolyticus and anaerobic gram-positive cocci to induce bacteraemia and seeding to various organs was investigated. The test species were injected into mice subcutaneously alone, or mixed with other aerobic or facultative organisms. Capsulate anaerobes were isolated more frequently from the blood, spleen, liver, and kidneys of infected animals than were non-capsulate organisms. After injection of single anaerobic strains, capsulate organisms were recovered from 163 (39%) of 420 animals; non-capsulate anaerobes were recovered from only 14 (3%) of 420 animals. After injection of B. fragilis mixed with aerobic or facultative organisms, the capsulate B. fragilis strain was isolated more often and for longer periods than the non-capsulate strain. Capsulate B. fragilis was also recovered more often 5 days after injection with other organisms, than when injected alone. These data demonstrate that capsulate Bacteroides spp. and anaerobic gram-positive cocci are more virulent than non-capsulate strains in single and mixed infections.
Abscess↗
Comparison of two transport systems for recovery of aerobic and anaerobic bacteria from abscesses.
An evaluation of two commercially available swab transport systems, Port-A-Cul (PAC; BBL Microbiology Systems, Cockeysville, Md.) and Anaerobic Specimen Collector (ASC; Becton Dickinson Vacutainer Systems, Rutherford, N.J.), in the recovery of organisms from clinical specimens was done. Fifteen abscesses were drained, and swabs of their contents were placed in the transport systems until they were inoculated for detection of aerobic and anaerobic bacteria. The swabs were plated immediately after collection and after delays of 4, 24, 48, and 72 h. A total of 70 bacterial isolates, 47 anaerobes and 23 aerobes, were recovered from specimens inoculated immediately after collection. The survival of anaerobic bacteria was better in the PAC system than in the ASC system. This was evident as the length of delay in cultivation was extended. At 4 h, 46 anaerobic isolates were recovered in the PAC system, compared with 39 in the ASC system (P less than 0.1). At 24 h, 45 isolates were recovered in the PAC system and 26 isolates were recovered in ASC (P less than 0.001); at 48 h, 40 were recovered in PAC and 15 were recovered in ASC; and at 72 h, 32 were recovered in PAC and 6 were recovered in ASC. There were no differences between the systems in the recovery of aerobic bacteria. These data demonstrate the usefulness of the PAC system in the recovery of anaerobes and the need for quality control of all transport systems for anaerobic bacteria.
Abscess↗
Recovery of beta-lactamase producing bacteria in pediatric infections.
The presence of beta-lactamase producing bacteria (beta LPB) was investigated in specimens obtained from 1469 children who presented with infections of the skin and soft tissue (648), upper respiratory tract (514), pulmonary sites (137), surgical sites (113), and other (57). Of 4989 bacterial isolates recovered, 910 (18%) were beta LPB, 492 (54%) aerobes, and 418 (46%) anaerobes. The beta LPB were recovered in 751 (51%) of the children. The most frequently recovered beta LPB was Staphylococcus aureus, which was recovered in 356 (47%) patients. Most isolates were recovered from patients with skin and soft-tissue infections (68% of patients), upper respiratory tract infections (49%), and pulmonary infections (35%). Bacteroides fragilis group was isolated in 35% of patients with beta LPB, mostly from surgical infections (98% of patients), pulmonary infections (36%), skin and soft-tissue infections (25%), and upper respiratory tract infections (20%). Twenty-five percent of the Bacteroides melaninogenicus group produced beta-lactamase. These organisms were recovered in 15% of patients with beta LPB. They were recovered in upper respiratory tract infections (38% of patients), pulmonary infections (22%), and skin and soft-tissue infections (7%). Other beta LPB were Pseudomonas aeruginosa (8% of total patients with beta LPB), Escherichia coli (4%), Bacteroides oralis (3%), Klebsiella pneumoniae (3%), Haemophilus influenzae (2%), Proteus (1%), and Branhamella catarrhalis (1%). The role of beta LPB in the failure of penicillin to eradicate many of the infections is discussed.
Bacteria↗
Role of encapsulated anaerobic bacteria in synergistic infections.
The effect of encapsulation on the virulence, survival, and protection of anaerobic bacteria from phagocytosis is reviewed. Support for the importance of encapsulated Bacteroides sp. and anaerobic and facultative Gram-positive cocci (AFGPC) was provided by their higher recovery rate in oropharyngeal infections, compared to their number in the normal oral flora. Studies of the pathogenicity of anaerobic bacteria of the Bacteroides, Fusobacterium, and Clostridium genera and AFGPC are also presented. The organisms were inoculated into mice and their ability to induce subcutaneous abscesses was determined. Encapsulated Bacteroides, Fusobacteria, and AFGPC generally induced abscesses, whereas unencapsulated organisms did not. However, many of the strains that had only a minimal number of encapsulated organisms (less than 1%) survived in the abscess, and became heavily encapsulated when inoculated with other viable or nonviable encapsulated bacteria. These strains were thereafter able to induce abscesses when injected alone. Encapsulated Bacteroides sp. and anaerobic cocci induced bacteremia and translocation, and increased the mortality of the infected animals more often than did the unencapsulated form of the same strains. The relative importance of encapsulated anaerobes in relation to their aerobic and facultative counterparts in mixed infection was studied, using selective antimicrobial therapy and quantitative cultures of abscesses induced in mice. With few exceptions, possession of a capsule made Bacteroides sp. more important than their aerobic counterparts. Synergistic potentials were seen between encapsulated Bacteroides sp. and all tested aerobic bacteria and most AFGPC, and between most AFGPC and Pseudomonas aeruginosa or Staphylococcus aureus. These studies demonstrated the importance of encapsulated anaerobes in mixed infections.
Abscess↗
The clinical microbiology of Waldeyer's ring.
The role of microorganisms in infections of Waldeyer's ring is reviewed. The agents involved are aerobic and anaerobic bacteria, viruses, chlamydia, fungi, parasites, and rickettsia. The therapeutic implications of the presence of beta-lactamase-producing bacteria are discussed.
Adenoids↗
Effect of prophylactic antibiotics upon mixed infections with Bacteroides fragilis.
Antimicrobial agents were used alone or in combinations to explore the effect of prophylactic antimicrobial therapy. Subcutaneous abscesses in mice were induced by single and mixed infections of Bacteroides fragilis, Staphylococcus aureus, Group A streptococci and Escherichia coli. The infected mice were treated with three doses of gentamicin, cefoxitin, metronidazole or clindamycin alone or else metronidazole or clindamycin in combination with gentamicin. Mice were sacrificed five days after inoculation and the bacterial contents of the abscesses were determined. Infection induced by a single bacteria always responded to appropriate antimicrobial therapy. However, in infections caused by two organisms, therapy directed at either the Bacteroides fragilis (with metronidazole or clindamycin) or Escherichia coli (with gentamicin) was effective in not only significantly reducing the colony forming units (CFU) of the target organism but also reducing the number of untreated bacteria. Clindamycin alone was effective in reducing the CFU of both components of mixed infections of Bacteroides fragilis with either Staphylococcus aureus or Group A streptococci. Cefoxitin alone and the combination of either clindamycin or metronidazole with gentamicin were effective against all mixed infections. These data support the need to provide coverage for all components of mixed infections with single or combination therapy.
Abscess↗
Direct and indirect pathogenicity of anaerobic bacteria in respiratory tract infections in children.
Bacteroides sp (Bacteroides melaninogenicus, Bacteroides oralis, and Bacteroides fragilis), peptostreptococci, and fusobacteria are important pathogens in respiratory tract infections (RTI). These organisms are often recovered mixed with other aerobic, facultative, and anaerobic bacteria. Evidence supporting their virulence is provided by studies showing their synergistic potentials in mixed infections and their increased virulence when encapsulated. A recent increase in numbers of beta-lactamase producing strains of anaerobic gram-negative bacteria in RTI has been associated with increased failure rates of penicillins in eradication of these infections. These infections include chronic otitis media, chronic sinusitis and mastoiditis, chronic recurrent tonsillitis, and lung abscesses. The pathogenicity of these organisms is apparent through their ability not only to survive penicillin therapy but also to protect penicillin susceptible pathogens from that drug. These direct and indirect virulence characteristics of anaerobic bacteria require the administration of appropriate antimicrobial therapy directed against all pathogens in mixed infections. The synergy that exists between different aerobic and anaerobic organisms in the respiratory tract is due to several pathogenic mechanisms. These mechanisms include the production of a capsule, which protects organisms from phagocytosis, and the production of beta-lactamase, which inactivates penicillins and first-generation cephalosporins. Both of these mechanisms enhance infection and induce complications. However, more work is necessary to prevent encapsulation and the production of enzymes. Data, thus far, indicate that there are therapeutic modalities that can be used to prevent these occurrences and eliminate many mixed RTI.
Animals↗