Synthesis of novel cyclic protease inhibitors using Grubbs olefin metathesis

The microbiologic features of infected sinus aspirates in nine children with neurologic impairment were studied. Anaerobic bacteria, always mixed with aerobic and facultative bacteria, were isolated in 6 (67%) aspirates and aerobic bacteria only in 3 (33%). There were 24 bacterial isolates, 12 aerobic or facultative and 12 anaerobic. The predominant aerobic isolates were Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus (2 each) and Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae (1 each). The predominant anaerobes were Prevotella sp. (5), Peptostreptococcus sp. (4), Fusobacterium nucleatum (2), and Bacteroides fragilis (1). Beta-lactamase-producing bacteria were isolated from 8 (89%) patients. Organisms similar to those recovered from the sinuses were also isolated from tracheostomy site and gastrostomy wound aspirates in five of seven instances. This study demonstrates the uniqueness of the microbiologic features of sinusitis in neurologically impaired children, in which, in addition to the organisms known to cause infection in children without neurologic impairment, facultative and anaerobic gram-negative organisms that can colonize other body sites are predominant.     

Aerobic and anaerobic microbiology of empyema. A retrospective review in two military hospitals

The microbiology and clinical features of empyema were studied retrospectively in 197 patients whose specimens yielded bacterial growth after inoculation for aerobic and anaerobic bacteria. Three hundred forty-three organisms (216 aerobic or facultative and 127 anaerobic organisms) were isolated. Aerobic bacteria were isolated in 127 (64 percent) patients, anaerobic bacteria in 25 (13 percent), and mixed aerobic and anaerobic bacteria in 45 (23 percent). The predominant aerobic or facultative organisms were Streptococcus pneumoniae (70 isolates), Staphylococcus aureus (58), Escherichia coli (17), Klebsiella pneumoniae (16), and Haemophilus influenzae (12). The predominant anaerobes were pigmented Prevotella and Porphyromonas species (24), Bacteroides fragilis group (22), anaerobic cocci (36), and Fusobacterium species (20). beta-Lactamase-producing organisms were recovered in 49 (38 percent) of 128 tested specimens. These included all 42 tested S aureus and 15 B fragilis group, 4 of 9 K pneumoniae, 3 of 9 H influenzae, 3 of 8 pigmented Prevotella and Porphyromonas species, and 2 of 6 E coli. Most patients from whom S pneumoniae and H influenzae were recovered had pneumonia, and most patients with S aureus had pneumonia, aspiration pneumonia, and lung abscesses. The recovery of anaerobic bacteria was mostly associated with the concomitant diagnosis of aspiration pneumonia, and lung, subdiaphragmatic, dental, and oropharyngeal abscesses. These data highlight the importance of anaerobic bacteria in selected cases of empyema.     

Relationship between nasopharyngeal colonization and the development of otitis media in children. Tonawanda/Williamsville Pediatrics

Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis are the predominant bacteria associated with otitis media. A cohort of 306 infants was followed from birth through 12 months to determine frequency and duration of colonization and risk of acute otitis media (AOM) and otitis media with effusion (OME). M. catarrhalis was the most common bacterium isolated. Infants colonized at < or = 3 months of age were at increased risk of AOM and OME. Early colonization with M. catarrhalis revealed the greatest risk (relative risk [RR] = 1.24), especially for OME (RR = 1.57). There was a strong relationship between the frequency of colonization and OM (r = .37, P < .001,) for each pathogen. Although S. pneumoniae, nontypeable H. influenzae, and M. catarrhalis are part of the normal nasopharyngeal flora during infancy, an increased rate of colonization may identify a subpopulation of children that is at increased risk of OM.     

Efficacy of itraconazole in children with Trichophyton tonsurans tinea capitis

The microbiology of needle aspirates from 40 inflamed cervical lymph glands was studied for aerobic and anaerobic bacteria, fungi and mycobacteria. Forty-two bacterial, 11 mycobacterial and six fungal isolates were isolated. Aerobic bacteria only were recovered in 11 (27.5%), anaerobes alone in five (12.5%) and mixed aerobic and anaerobic bacteria in seven (17.5%). Mycobacterium sp. were recovered in 11 (27.5%) and fungi in six (15%). The recovery of anaerobes was associated with dental infection. Eighteen aerobic bacteria were isolated and the predominant ones were Staphylococcus aureus (eight isolates) and group A streptococci (four). Twenty-four anaerobic bacteria were recovered and the predominant ones were: Prevotella sp. (six), Peptostreptococcus sp. (five), Propionibacterium acnes (four) and Fusobacterium sp. (three). These findings demonstrate the role of anaerobic organisms in cervical lymphadenitis and the need to culture aspirated material from the glands for both aerobic and anaerobic microorganisms.     

Anaerobic bacteria isolated from appendices and appendicitis cases

Anaerobic bacteria were isolated from 17 of 40 normal appendices and appendicitis cases in Ankara. In both cases gram positive, nonsporulating, and gram negative organisms were isolated. Gram positive cocci were only isolated from appendicitis cases. The bacteria isolated from appendicitis are usually like the anaerobic bacteria of the colon flora. All anaerobic bacteria in appendix flora can cause appendicitis in suitable conditions.     

Aerobic and anaerobic bacteriology of cutaneous abscesses in children

Specimens from 209 cutaneous abscesses in children were cultured for aerobic and anaerobic microorganisms. Of these, nine (4%) were sterile and 51 (24%) yielded pure cultures that were predominantly Staphylococcus aureus. The rest of the abscesses yielded growth of two or more aerobic and/or anaerobic organisms. The data were organized according to these anatomic locations: head, neck, trunk, finger, nailbed, hand, leg, buttocks, perirectal, and vulvovaginal areas. Aerobic bacteria only were present in 92 specimens (46%), anaerobes only were isolated in 52 (26%), and mixed aerobic and anaerobic bacteria were present in 56 abscesses (28%). A total of 467 isolates (270 anaerobes and 197 aerobes) were recovered, accounting for 2.3 isolates per specimen (1.3 anaerobes and 1.0 aerobes). The presence of more than one anaerobe per abscess was obtained from the vulvo-vaginal, buttocks, perirectal, finger, nailbed, and head areas. Aerobes were more prevalent in the neck, hand, leg, and trunk areas. The predominant aerobes recovered were: S aureus (89 isolates), alpha- and nonhemolytic streptococci (29), group A beta-hemolytic streptococci (16), Enterobacter (10), and Escherichia coli (8). The predominant anaerobes recovered were anaerobic Gram-positive cocci (79 isolates), Bacteroides sp (116, including 31 B melaninogenicus group and 29 B fragilis group), and Fusobacterium sp (39). Our findings indicate the polymicrobial nature and predominance of anaerobes in cutaneous abscesses in children in perirectal, head, finger, and nailbed areas.     

Moraxella (Branhamella) catarrhalis: its isolation in the respiratory secretions of adult patients

OBJECTIVE: We have designed a retrospective study in order to know the clinical significance of the isolation of Moraxella (Branhamella) catarrhalis (MC) in respiratory specimens of adult hospitalized patients. METHODS: We performed a Gram stain and culture on blood-agar, MacConkey media and quantitative culture in chocolate-agar to all respiratory samples. In patients with a clinical diagnosis of pneumonia BCYE-alpha was added. During 2 years (1992-1993) MC was isolated in respiratory specimens from 52 patients. We revised the clinical history of all these patients. RESULTS: MC was isolated in 60 respiratory specimens (sputum and/or tracheobronchial aspirates) from 52 patients. The Gram stain showed gram-negative cocci in 77% and gram-positive cocci in 17% of the cases. MC grew in pure culture in 28 specimens (46.6%). In 23% of cases MC was isolated with Streptococcus pneumoniae and in 21% with Haemophilus influenzae. Fifty-two stocks (86.6%) produced beta-lactamase. Twelve patients had a clinical diagnosis of pneumonia, 8 of them had an underlying chronic respiratory disease. Other 24 patients with an underlying chronic respiratory disease had a bronchial infection as a cause of exacerbation of their respiratory disease. Seven patients without an underlying chronic respiratory disease had a clinical episode of acute bronchitis. Finally, in 9 patients the isolation of MC was considered a colonization. CONCLUSIONS: In 17% cases MC was identified as a gram-positive cocci in the Gram stain, which may cause false diagnosis. The etiological importance of MC in episodes of acute exacerbation of patients with an underlying chronic respiratory disease is high.     

Microbiological investigation of Bartholin's gland abscesses and cysts

Percutaneous aspirates from intact Bartholin's gland cysts (12) and abscesses (34) were examined for bacteria and genital mycoplasmas. Aspirates from 10 of the 12 patients with Bartholin's gland cysts were sterile. Aspirates from the other two cysts contained organisms that are part of the vaginal microbial flora. Of the 34 abscesses, 24 (70.6 per cent) contained bacteria. Eight abscesses contained gram-negative rods in pure culture and four contained gonococci in pure culture. Twelve abscesses contained one or more vaginal organisms including anaerobic gram-negative rods (eight isolates), anaerobic gram-positive cocci (eight), Staphylococcus epidermidis (four), and microaerophilic streptococci (three). Although most of the patients had genital mycoplasmas isolated from vaginal cultures, Mycoplasma hominis was isolated from only one and Ureaplasma urealyticum from none of the aspirates.     

New closed-form expressions for the estimation of arterial windkessel compliance

Despite advances in public health and medical care, chronic suppurative otitis media is still prevalent around the world. It is most common in developing countries and in certain high risk populations in developed nations, as well as among children who have tympanostomy tubes inserted. Since this chronic infection is caused by persistent acute otorrhea, which in turn is usually secondary to acute otitis media, prevention should be directed toward prompt and appropriate treatment of the acute middle-ear infection. Repair of chronic perforations should prevent recurrence, since reinfection is due either to reflux of pathogenic organisms from the nasopharynx into the middle ear, or water contamination from the external canal. Information from epidemiological studies, which show that populations can be categorized into highest, high, low and lowest prevalence, can be helpful in setting national priorities for prevention and treatment.     

Dispersal of non-sporeforming anaerobic bacteria from the skin

Dispersal of non-sporeforming anaerobic bacteria was studied. Skin samples were taken from the subjects, and dispersed from different parts of the body was examined. The number of anaerobic bacteria dispersed was not correlated to their density on the surface of skin area exposed. The highest density of anaerobic bacteria on the skin was found in the face and upper trunk, but the highest yield of anaerobic bacteria dispersed came from the lower trunk. The dominant anaerobic bacteria dispersed were Propionibacterium acnes, but Propionibacterium avidum, Propionibacterium granulosum and Gram-positive cocci were also isolated from the dispersal samples. Peptococcus magnus was the most common coccus isolated. For the less frequently isolated bacteria, the best correlation was found between the perineal flora and airborne bacteria. A comparison was also made of bacterial dispersal by naked and dressed subjects. The dispersal of both aerobic and anaerobic bacteria was higher when the subjects were dressed in conventional operating theatre cotton clothing than when they were naked. The increased dispersal of anaerobic bacteria when the subjects were dressed was mainly due to increased dispersal of Propionibacterium sp.     

Gram-positive anaerobic cocci

Gram-positive anaerobic cocci (GPAC) are a heterogeneous group of organisms defined by their morphological appearance and their inability to grow in the presence of oxygen; most clinical isolates are identified to species in the genus Peptostreptococcus. GPAC are part of the normal flora of all mucocutaneous surfaces and are often isolated from infections such as deep organ abscesses, obstetric and gynecological sepsis, and intraoral infections. They have been little studied for several reasons, which include an inadequate classification, difficulties with laboratory identification, and the mixed nature of the infections from which they are usually isolated. Nucleic acid studies indicate that the classification is in need of radical revision at the genus level. Several species of Peptostreptococcus have recently been described, but others still await formal recognition. Identification has been based on carbohydrate fermentation tests, but most GPAC are asaccharolytic and use the products of protein degradation for their metabolism; the introduction of commercially available preformed enzyme kits affords a physiologically more appropriate method of identification, which is simple and relatively rapid and can be used in routine diagnostic laboratories. Recent reports have documented the isolation in pure culture of several species, notably Peptostreptococcus magnus, from serious infections. Studies of P. magnus have elucidated several virulence factors which correlate with the site of infection, and reveal some similarities to Staphylococcus aureus. P. micros is a strongly proteolytic species; it is increasingly recognized as an important pathogen in intraoral infections, particularly periodontitis, and mixed anaerobic deep-organ abscesses. Comparison of antibiotic susceptibility patterns reveals major differences between species. Penicillins are the antibiotics of choice, although some strains of P. anaerobius show broad-spectrum beta-lactam resistance.     

Use of the BacT/Alert blood culture system for culture of sterile body fluids other than blood

Studies have demonstrated that large-volume culture methods for sterile body fluids other than blood increase recovery compared to traditional plated-medium methods. BacT/Alert is a fully automated blood culture system for detecting bacteremia and fungemia. In this study, we compared culture in BacT/Alert standard aerobic and anaerobic bottles, BacT/Alert FAN aerobic and FAN anaerobic bottles, and culture on routine media for six specimen types, i.e., continuous ambulatory peritoneal dialysate (CAPD), peritoneal, amniotic, pericardial, synovial, and pleural fluids. Specimen volumes were divided equally among the three arms of the study. A total of 1,157 specimens were tested, with 227 significant isolates recovered from 193 specimens. Recovery by method was as follows: standard bottles, 186 of 227 (82%); FAN bottles, 217 of 227 (96%); and routine culture, 184 of 227 (81%). The FAN bottles recovered significantly more gram-positive cocci (P < 0.001), Staphylococcus aureus (P = 0.003), coagulase-negative staphylococci (P = 0.008), gram-negative bacilli (P < 0.001), Enterobacteriaceae (P = 0.005), and total organisms (P < 0.001) than the routine culture. There were no significant differences in recovery between the standard bottles and the routine culture. The FAN aerobic bottle recovered significantly more gram-positive cocci (P < 0.001), S. aureus isolates (P < 0.001), coagulase-negative staphyococci (P = 0.003), and total organisms (P < 0.001) than the standard aerobic bottle, while the FAN anaerobic bottle recovered significantly more gram-positive cocci (P < 0.001), S. aureus isolates (P < 0.001), Enterobacteriaceae (P = 0.03), and total organisms (P < 0.001) than the standard anaerobic bottle. For specific specimen types, significantly more isolates were recovered from the FAN bottles compared to the routine culture for synovial (P < 0.001) and CAPD (P = 0.004) fluids. Overall, the FAN bottles were superior in performance to both the standard bottles and the routine culture for detection of microorganisms from the types of sterile body fluids included in this study.     

Microbiology of common infections in the upper respiratory tract

The management of upper respiratory tract infections has become more difficult because of the recent increase in the number of penicillin-resistant organisms. The bacteria that predominate in otitis media and sinusitis can resist penicillin through the production of the enzyme beta-lactamase (Haemophilus influenzae and Moraxella catarrhalis in acute infections and Staphylococcus aureus and Prevotella and Fusobacteria spp in chronic infections) or through changes in penicillin-binding sites (Streptococcus pneumoniae). beta-lactamase-producing bacteria can express their pathogenicity directly through their ability to cause infections and indirectly by production of the enzyme, thus protecting penicillin-susceptible pathogens from penicillins. This phenomenon may explain penicillin's failure in the treatment of Group A beta-hemolytic streptococcal (GABHS) tonsillitis. An additional cause for penicillin failure is the absence among the normal tonsillar bacterial flora of streptococcal species that are capable of interfering with the growth of GABHS. Proper use of antimicrobial therapy, including those therapies that are effective against penicillin-resistant bacteria, is the cornerstone of management of upper respiratory tract infections.     

Significance of normal oropharyngeal flora in the development of streptococcal pharyngitis and outcome of penicillin therapy

Pharyngitis is one of the most frequent diseases in children. The most important of the bacterial infections is due to Streptococcus pyogenes. For many years, penicillin is considered to be the drug of choice for streptococcal pharyngitis, although failure rates of up to 20% have been reported. One of possible explanations for penicillin treatment failure is presence of other species of bacteria in the normal oropharyngeal flora that can interfere with colonization and growth of Streptococcus pyogenes and influence the development of pharyngitis. A wide variety of microorganisms, including alpha-haemolytic streptococci and anaerobic bacteria, are present within the oropharynx (table 1). The strain of alpha-haemolytic streptococci is in interference with Streptococcus pyogenes. By producing bacteriocins, they inhibit colonization and growth of Streptococcus pyogenes and assist in its eradication. Anaerobic bacteria may play a direct or indirect role in development of pharyngitis. They may be directly responsible for specific forms of pharyngitis or contribute indirectly with possibility of synergy between them and Streptococcus pyogenes. Beta-lactamase-producing aerobic and anaerobic organisms may contribute to penicillin treatment failure. By producing beta-lactamase within the tonsillar tissue, they destroy penicillin and protect streptococci from the antibacterial effect of penicillin. Pharyngeal bacterial flora may vary according to the state of the patient (Figure 1). During an acute infection and in the cases of treatment failure and recurrent pharyngitis the number of alpha-haemolytic streptococci declines, while there is an increase in the number of anaerobic and beta-lactamase-producing organisms. After successful treatment the number and type of bacteria is similar to those found within normal tissue. Knowing the distribution and changes in pharyngeal bacterial flora is important for choosing the optimal drug for treatment of streptococcal pharyngitis. Although penicillin reduces the number of interfering beta-haemolytic streptococci, because of its advantages, if remains the drug of choice for the treatment of streptococcal pharyngitis. In cases of treatment failure and recurrent infections cephalosporins and macrolides may be a useful alternative to penicillin because they possess relatively poor activity against alpha-haemolytic streptococci, resistance to beta-lactamase and because of better penetration into tonsilar tissue.     

Microbiology of liver and spleen abscesses

To study the aerobic and anaerobic microbiology of liver and spleen abscesses and correlate the results with predisposing factors, potential causes and routes of infection, clinical and laboratory data of 48 patients with liver abscesses and 29 with spleen abscesses treated between 1970 and 1990 were reviewed retrospectively. In liver abscesses, a total of 116 isolates (2.4 isolates/specimen) was obtained; 43 were aerobic and facultative species (0.9 isolates/specimen) and 73 were anaerobic species or microaerophilic streptococci (1.5 isolates/specimen). Aerobic bacteria only were isolated from 12 (25%) abscesses, anaerobic bacteria only from eight (17%), and mixed aerobic and anaerobic bacteria from 28 (58%); polymicrobial infection was present in 38 (79%). The predominant aerobic and facultative isolates were Escherichia coli (11 isolates), Streptococcus group D (8), Klebsiella pneumoniae (5) and Staphylococcus aureus (4). The predominant anaerobes were Peptostreptococcus spp. (18 isolates), Bacteroides spp. (13), Fusobacterium spp. (10), Clostridium spp. (10) and Prevotella spp. (4). There were 12 isolates of micro-aerophilic streptococci. S. aureus and beta-haemolytic streptococci were associated with trauma; Streptococcus group D, K. pneumoniae and Clostridium spp. with biliary disease; and Bacteroides spp. and Clostridium spp. with colonic disease. In splenic abscesses, a total of 56 isolates (1.9 isolates/specimen) was obtained; 23 were aerobic and facultative species (0.8 isolates/specimen), 31 were anaerobic species or micro-aerophilic streptococci (1.1 isolates/specimen) and two were Candida albicans. Aerobic bacteria only were isolated from nine (31%) abscesses, anaerobic bacteria from eight (28%), mixed aerobic and anaerobic bacteria from 10 (34%) and C. albicans in two (7%); polymicrobial infection was present in 16 (55%). The predominant aerobic and facultative isolates were E. coli (5 isolates), Proteus mirabilis (3), Streptococcus group D (3), K. pneumoniae (3) and S. aureus (4). The predominant anaerobes were Peptostreptococcus spp. (11 isolates), Bacteroides spp. (5), Fusobacterium spp. (3) and Clostridium spp. (3). S. aureus, K. pneumoniae and Streptococcus group D were associated with endocarditis, E. coli with urinary tract and abdominal infection, Bacteroides spp. and Clostridium spp. with abdominal infection and Fusobacterium spp. with respiratory infection.     

Intellectual level (IQ) in heterozygotes for phenylketonuria (PKU). Is the PKU gene also acting by means other than phenylalanine-blood level elevation?

Wound infection in 239 patients who underwent cholecystectomy were analyzed retrospectively. Seventeen per cent of the patients with acute cholecystitis had wound infection compared with 8.9 per cent of patients with chronic cholecystitis. Bacteriology of wound infections revealed Staphylococcus aureus in 76.4 per cent of the chronic cholecystitis group and in 12.5 per cent of the acute cholecystitis group. Wound infection in the acute cholecystitis group involved gram-negative rods predominantly. Organisms were isolated from bile culture in 71.4 per cent of acute cholecystitis patients compared with 59.6 per cent of chronic cholecystitis patients. Of patients with positive bile cultures 11.3 per cent had wound infections compared with 6.8 per cent of patients with negative bile cultures. The most common organisms isolated from bile cultures with resultant wound infections were S epidermis, S aureus, and Klebsiella sp. Wound infection after cholecystectomy for chronic cholecystitis arises from external sources and not contaminated bile. Antibiotic therapy should be directed accordingly.     

Bacteriological study of otogenic cerebral abscesses: chemotherapeutic role of metronidazole

In nine consecutive patients with otogenic cerebral abscesses a mixed growth of aerobic and obligate anaerobic bacteria was isolated from the pus in five patients, and in the remaining four obligate anaerobes were the sole isolates. The commonest obligate anaerobe isolated was Bacteroides fragilis, which was present in all but one patient. The patients were all treated with metronidazole for the anaerobic organisms and with appropriate chemotherapy against the aerobic organisms isolated. All the patients recovered and only one was left with a neurological deficit. As otogenic cerebral abscesses constitute a major proportion of all cerebral abscesses, the use of metronidazole against obligate anaerobic bacteria, which tend to dominate in such abscesses, should reduce the high mortality from this condition.     

Local impairment of immunoreactivity in HIV-infected women with HPV-related squamous intraepithelial lesions of the cervix

The effect on the nasopharyngeal bacterial flora of therapy for 10 days with co-amoxiclav or cefprozil was studied in 50 children with acute otitis media. Before therapy, potential pathogens (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) were isolated in 14 (56%) of those treated with co-amoxiclav and 15 (60%) of those treated with cefprozil. Following therapy, the reduction in the number of these pathogens was the same in the two groups. However, differences between the groups were noted in the recovery of organisms with interfering capability, namely alpha-haemolytic streptococci, Peptostreptococcus anaerobius and Prevotella melaninogenica. Fifty interfering organisms were recovered from each group before therapy. After therapy with co-amoxiclav or cefprozil their number declined to 11 and 42, respectively (P< 0.001).     

Atmospheric growth requirements for Alloiococcus species and related gram-positive cocci

The growth of Alloiococcus otitis under different atmospheres and nutritional conditions was studied. The growth rates of 25 strains of gram-positive cocci representing five genera on heart infusion agar plates containing 5% rabbit blood and on brucella agar plates with and without sheep blood under aerobic, increased CO2, and anaerobic atmospheres were compared. Eight strains of alloiococci plated on heart infusion agar with rabbit blood and on brucella sheep blood agar grew under aerobic and candle jar atmospheres. Two of these strains showed poor anaerobic growth after 7 days. Strains of Aerococcus viridans, Aerococcus urinae, Helcococci kunzi, Dolosigranulum pigrum, Gemella haemolysans, and Gemella morbillorum grew well under all three atmospheres and on the three types of media and in thioglycolate broth. These results confirm all the aerobic atmospheric requirements for Alloiococcus strains and show that aerobic growth characteristics help distinguish the alloiococci from the other gram-positive cocci that are facultatively anaerobic.