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Lemierre's syndrome: the forgotten disease. An unusual presentation of sepsis.

A 19-year-old girl presented with a septical condition with fever of 40 degrees C, swelling of the right sternocleidomastoid region and abdominal pain. Except for a sore throat with pain strictly localized to the right side of her neck and fever over the last week there were no other clues in her past medical history. An abdominal ultrasound and MRT scan as well as a chest X-ray only showed non-specific findings. The diagnosis of Lemierre's syndrome was established by ultrasonographical detection of right jugular venous thrombosis and perivascular inflammation together with blood cultures positive for Fusobacteria. The patient recovered within days after treatment was initiated with metronidazol according to the antibiogram. Lemierre's syndrome is a life-threatening disease especially in an age group which is less frequently affected by septicaemia. A history of sore throat, Fusobacterium positive blood cultures and ultrasonographical detection of jugular venous thrombophlebitis together with the knowledge of the "forgotten disease" will lead the way to the diagnosis.

Adult↗

Antibacterial activity of amniotic fluid in the early third trimester. Its association with preterm labor and delivery.

The purpose of this study was to determine the bacterial growth inhibitory property of amniotic fluid (AF) from patients in the early third trimester and to examine its relationship to preterm labor and delivery. A total of 38 AF samples from patients between 27 and 35 weeks gestation with intact membranes were studied. Antibacterial activity was tested against Escherichia coli, Staphylococcus aureus, and Bacteroides fragilis. Fifteen fluids were from patients in preterm labor who delivered near term after successful inhibition of labor. Five of these fluids (33%) were inhibitory to E. coli, five (33%) to S. aureus, and 11 (73%) to B. fragilis. Nine fluids were from patients who failed inhibition of labor and delivered preterm; none of these were inhibitory to E. coli, two (22%) to S. aureus, and only one (11%) to B. fragilis (P less than 0.005). Two of the nine fluids from patients who failed inhibition of labor also yielded fusobacteria. The remaining 14 fluids were obtained from patients without preterm labor and exhibited antibacterial activity similar to that from patients with successful labor inhibition. Results suggest a relationship between the absence of AF antibacterial activity against B. fragilis and preterm delivery in patients with preterm labor and intact membranes.

Amniocentesis↗

Bacterial biota in the human distal esophagus.

The esophagus, like other luminal organs of the digestive system, provides a potential environment for bacterial colonization, but little is known about the presence of a bacterial biota or its nature. By using broad-range 16S rDNA PCR, biopsies were examined from the normal esophagus of four human adults. The 900 PCR products cloned represented 833 unique sequences belonging to 41 genera, or 95 species-level operational taxonomic units (SLOTU); 59 SLOTU were homologous with culture-defined bacterial species, 34 with 16S rDNA clones, and two were not homologous with any known bacterial 16S rDNA. Members of six phyla, Firmicutes, Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria, and TM7, were represented. A large majority of clones belong to 13 of the 41 genera (783/900, 87%), or 14 SLOTU (574/900, 64%) that were shared by all four persons. Streptococcus (39%), Prevotella (17%), and Veilonella (14%) were most prevalent. The present study identified approximately 56-79% of SLOTU in this bacterial ecosystem. Most SLOTU of esophageal biota are similar or identical to residents of the upstream oral biota, but the major distinction is that a large majority (82%) of the esophageal bacteria are known and cultivable. These findings provide evidence for a complex but conserved bacterial population in the normal distal esophagus.

Bacteria↗

Molecular analysis of the bacterial microbiota in the human stomach.

The microbiota of the human stomach and the influence of Helicobacter pylori colonization on its composition remain largely unknown. We characterized bacterial diversity within the human gastric mucosa by using a small subunit 16S rDNA clone library approach and analyzed 1,833 sequences generated by broad-range bacterial PCR from 23 gastric endoscopic biopsy samples. A diverse community of 128 phylotypes was identified, featuring diversity at this site greater than previously described. The majority of sequences were assigned to the Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria phyla. Ten percent of the phylotypes were previously uncharacterized, including a Deinococcus-related organism, relatives of which have been found in extreme environments but not reported before in humans. The gastric clone libraries from 19 subjects contained H. pylori rDNA; however, only 12 of these subjects tested positive for H. pylori by conventional laboratory methods. Statistical analysis revealed a large degree of intersubject variability of the gastric ecosystem. The presence of H. pylori did not affect the composition of the gastric community. This gastric bacterial rDNA data set was significantly different from sequence collections of the human mouth and esophagus described in other studies, indicating that the human stomach may be home to a distinct microbial eco-system. The gastric microbiota may play important, as-yet-undiscovered roles in human health and disease.

Adult↗

Microbiology profile in women with pelvic inflammatory disease in relation to IUD use.

OBJECTIVE: To study the microbial characteristics of patients with pelvic inflammatory disease (PID) and the possible impact of an intrauterine device (IUD) on the microbial environment in women presenting with PID. METHODS: Case-control study, investigating 51 women with acute PID and 50 healthy women. Endocervical specimens for microbiological investigation were obtained at gynaecological examination. RESULTS: IUD users with PID had significantly more Fusobacteria spp. and Peptostreptococcus spp. than non-IUD users with PID. The finding of combinations of several anaerobic or aerobic microbes was associated with a significantly increased risk of PID and with complicated PID. In IUD users, the combinations of several anaerobic/aerobic microbes were associated with an increased risk of PID, irrespective of duration of IUD use. Long-term IUD use appeared to be associated with an increased risk of a PID being complicated. CONCLUSION: The finding of several anaerobic or aerobic microbes appears to be associated with PID in users of IUD.

Adult↗

Antibiotic susceptibility of anaerobic bacteria in Europe.

Twenty-two laboratories in 15 European countries determined the MICs of 12 antibiotics for 1,289 isolates of the B. fragilis group by a microdilution method. There was no resistance to metronidazole (breakpoint, 8 mg/L), and only one isolate was found to be resistant to chloramphenicol (breakpoint, 8 mg/L). Resistance was uncommon to imipenem (0.3% at concentrations > 4 mg/L), amoxicillin/clavulanate (1% at concentrations > 8 mg/L), cefoxitin (3% at concentrations > 32 mg/L), mezlocillin (6% at concentrations > 64 mg/L), and clindamycin (9% at concentrations > 4 mg/L). The majority of the isolates were resistant to ampicillin (93% at concentrations > 4 mg/L), ciprofloxacin (56% at concentrations > 4 mg/L), and tetracycline (64% at concentrations > 4 mg/L). Bacteroides fragilis was the most susceptible species of the group, and the most striking regional differences in susceptibility were found in association with clindamycin and tetracycline; more resistance was noted in isolates from the southern part of Europe (Greece, Italy, Portugal, and Spain). It has been reported that Fusobacterium species and Clostridium species occasionally produce beta-lactamases. A few metronidazole-resistant Clostridium perfringens strains but no metronidazole-resistant fusobacteria have been isolated.

Bacteria, Anaerobic↗

How far should a clinical laboratory go in identifying anaerobic isolates, and who should pay?

Identification of anaerobic bacteria in specimens from sites of infection due to mixed organisms can be time-consuming and expensive. Laboratories should limit anaerobic workups by testing only those specimens that have been properly collected and transported to the laboratory. Use of selective and differential media for initial processing can provide rapid and relevant information to the clinician. Anaerobes isolated from normally sterile sites and sites of serious infection should always be completely identified. Group- or genus-level identifications may suffice in other instances. The Bacteroides fragilis group of organisms should always be identified because of their virulence and resistance to many antimicrobial agents. Some of the other organisms that warrant identification include Clostridium septicum (associated with gastrointestinal malignancy); Clostridium ramosum, Clostridium innocuum, and Clostridium clostridioforme (which are resistant to antibiotics); Clostridium perfringens (a cause of potentially serious infection); anaerobic cocci (which may be resistant to metronidazole and clindamycin); and fusobacteria (which may be virulent and resistant to clindamycin and penicillin).

Bacteria, Anaerobic↗

Effect of cefoperazone on faecal flora.

The effect of cefoperazone on the intestinal flora was investigated in 29 patients receiving the drug for 7 to 14 days. Faecal specimens were cultured quantitatively for aerobic and anaerobic micro-organisms before, during and after therapy. The cefoperazone treatment was associated with major changes in the faecal flora. There was marked suppression of enterobacteria, staphylococci, streptococci, anaerobic cocci, bacteroides, fusobacteria, bifidobacteria, eubacteria and lactobacilli. The number of enterococci increased in most patients and the number of clostridia remained constant. Eight patients had cultures positive for Clostridium difficile during or after treatment. The marked changes in the intestinal flora can have important clinical consequences.

Adolescent↗

Impact of single dose as compared to three dose prophylaxis with latamoxef (moxalactam) on the colonic microflora in patients undergoing colorectal surgery.

Twenty patients undergoing colorectal surgery were given an initial dose of 2 g latamoxef (moxalactam) parenterally at the induction of anaesthesia. Ten of the patients received two subsequent doses at 8 h intervals. A series of serum and faecal specimens were taken for analysis of latamoxef concentrations. Tissue samples from intestinal mucosa and peritoneal fat were also taken at surgery. The mean serum peak level was 119.8 +/- 10.7 mg/l. The mean half life was 2.8 h and the mean area under the serum concentration curve was 345.0 +/- 25.7 mg h/l. The concentrations in intestinal mucosa were high when the tissue was removed within 4 h after the administration of latamoxef (22.6 +/- 1.7 micrograms/g, mean +/- S.E.). The concentrations declined when the tissues were removed later (7.8 +/- 0.7 micrograms/g). The content of latamoxef in peritoneal fat varied, range 0.8-23.4, mean 8.5 +/- 1.4 micrograms/g. Measureable levels of latamoxef in faeces were found in all patients except one. The values varied between 0.2 to 23.0, mean 8.9 +/- 1.5 micrograms/g. Faecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. The aerobic bacteria-streptococci, enterococci and enterobacteria--were suppressed significantly during the prophylaxis period. Among the anaerobic bacteria--cocci, lactobacilli, bifidobacteria, clostridia, bacteroides and fusobacteria--decreased markedly during the same period. After two weeks the microflora was normalized in all patients. There were no differences between the patients receiving one dose of latamoxef and those receiving three doses. No postoperative infections occurred.

Adult↗

Comparative in-vitro activity of Sch 34343 for a wide spectrum of clinically significant anaerobic bacteria.

One hundred and fifty strains of anaerobic bacteria including 45 bacteroides, 19 fusobacteria, 41 cocci, 34 clostridia, and 11 Gram-positive non-sporeforming rods were tested by agar dilution for their susceptibilities to cefoxitin, cefuroxime, latamoxef (moxalactam), penicillin G, chloramphenicol, clindamycin, metronidazole and Sch 34343. Excluding the 34 clostridia, 115 of the 116 remaining strains were inhibited by less than or equal to 1 mg/l of Sch 34343. One isolate of Bacteroides fragilis required 32 mg/l for inhibition. All of the 34 clostridia were inhibited by less than or equal to 8 mg/l of Sch 34343: 14 isolates of Clostridium difficile had an MIC50 and an MIC90 of 4 mg/l, whereas the remaining 20 species of clostridia had an MIC50 of 0.125 mg/l and an MIC90 of 2 mg/l. On a weight basis, Sch 34343 was generally more active than any of the seven other antimicrobial agents tested.

Anti-Bacterial Agents↗

Activity of pefloxacin and thirteen other antimicrobial agents in vitro against isolates from hospital and genitourinary infections.

The in-vitro activity of the quinolone derivative pefloxacin was compared with that of three other quinolones, five beta-lactam antibiotics and three aminoglycosides against 367 isolates from hospital patients and from out-patients with genitourinary infections. MIC90 of pefloxacin and norfloxacin for each strain was the same; that of ciprofloxacin was a little lower. All strains except Escherichia coli were resistant to nalidixic acid. Pefloxacin was highly active against Staphylococcus aureus (39 strains; MIC90 1.0 mg/l) and most strains of coagulase-negative staphylococci (56; 4 mg/l), Esch. coli (50; 0.25 mg/l), other enterobacteria (33; 1.0 mg/l) and Pseudomonas aeruginosa 6; 0.25 mg/l). With Bacteroides spp. (total 78; 64 mg/l), the fragilis group (23) and the fusobacteria (19) were resistant, but the melaninogenicus-oralis group (31; range 0.06- greater than 64 mg/l) and B. ureolyticus (22; 0.125- greater than 64 mg/l) gave variable results. Amongst genitourinary isolates, Neisseria gonorrhoeae (15) and Haemophilus ducreyi (34) were sensitive (less than 0.06 mg/l) but Gardnerella vaginalis (25) and Mobiluncus spp. (11) were resistant (32 mg/l). Pefloxacin was more active than ceftazidime, cefotaxime, ceftizoxime, latamoxef and piperacillin against S. aureus and coagulase-negative staphylococci and than gentamicin, tobramycin and amikacin against coagulase-negative staphylococci. No enterobacteria or pseudomonads were resistant to pefloxacin or other quinolones, whereas some were resistant to beta-lactams and aminoglycosides.

Anti-Bacterial Agents↗

The effect of quinolone antibacterials on the gastrointestinal flora compared with that of other antibacterials.

Although there is limited information on some of the newer quinolones it is likely that all such agents have a similar effect on the faecal flora. Ciprofloxacin seems to be best studied, and typical changes include regular and complete suppression of the enterobacteria and a slight diminution of enterococci. Total counts of anaerobic flora remain virtually unchanged, although small reductions have been noted in some studies for bacteroids, anaerobic cocci, fusobacteria and anaerobic non-sporing Gram-positive bacilli. Overgrowth of yeasts was not seen except when administration was prolonged. The results so far suggest that the newer quinolones will have a useful role in selective gut decontamination, the prevention of reinfection of the urinary tract, and the treatment of intestinal infection. Such early clinical results as have been published confirm this view. Of the other antibacterial agents discussed only some recent cephalosporins (cefotaxime, ceftazidime), aztreonam, cotrimoxazole and aminoglycosides have effects on the faecal flora similar to those of the newer quinolones. The remaining agents either have little or no effect or produce changes, such as a marked reduction in anaerobic flora, which are generally considered to be undesirable.

Anti-Bacterial Agents↗

Susceptibility of 539 gram-positive and gram-negative anaerobes to new agents, including RP59500, biapenem, trospectomycin and piperacillin/tazobactam.

Susceptibilities of 539 Gram-positive and Gram-negative anaerobes were tested by agar dilution against 15 new and existing antimicrobial agents. Organisms included 218 Bacteroides fragilis group strains, 15 non-fragilis group Bacteroides, 130 Porphyromonas/Prevotella, 49 fusobacteria, 50 peptostreptococci, 53 clostridia and 24 Gram-positive non-sporeforming bacilli. Of 412 Gram-negative bacilli, 89% were beta-lactamase-positive, while only two of the Gram-positive strains (both clostridia) produced this enzyme. Using established and preliminary breakpoints, all strains were susceptible to biapenem and imipenem (MIC90s 1 mg/L) and chloramphenicol (MIC90 8 mg/L). Only one of all the strains tested (a Cl. innocuum) was resistant (MIC > 4 mg/L) to RP59500; the latter had MIC90 2 mg/L, while 98% of strains were susceptible to trospectomycin (MIC90 16 mg/L). Ninety-nine per cent of strains were susceptible to piperacillin/tazobactam (MIC90 8 mg/L) compared to 86% to piperacillin (MIC90 > 64 mg/L). Corresponding data for ticarcillin/clavulanate versus ticarcillin were 97% susceptible (MIC90 8 mg/L) compared to 83% (MIC90 > 64 mg/L). Enhancement of the beta-lactam by the inhibitors was only seen in beta-lactamase-producing strains. Amoxycillin and cefoperazone were less often active (36% susceptible, MIC90 > 256 mg/L and 66% susceptible, MIC90 64 mg/L, respectively). Cefoxitin had greater activity than cefotetan (90% susceptible, MIC90 32 mg/L, compared to 72% susceptible, MIC90 > 64 mg/L). Metronidazole was active against 94% of strains (MIC90 4 mg/L). All metronidazole-resistant strains were Gram-positive (75% of non-sporeforming bacilli, 9% of clostridia and 6% of peptostreptococci). Ninety per cent of strains were susceptible to clindamycin (MIC90 4 mg/L).

Anti-Bacterial Agents↗

Anti-anaerobic activity of erythromycin, azithromycin and clarithromycin: effect of pH adjustment of media to compensate for pH shift caused by incubation in CO2.

The activity of erythromycin, azithromycin and clarithromycin against 112 anaerobes was tested by the Oxyrase agar dilution MIC method at pH 7.2 without supplemental CO2 and by an agar dilution MIC method in CO2 with media adjusted to pH 8.0. MICs (mg/L) of erythromycin, azithromycin and clarithomycin against Bacteroides fragilis ATCC 25285 and Bacteroides thetaiotaomicron ATCC 29741 were similar by the two methods. MICs for 94 clinical isolates tested by the two methods were within two dilutions of each other. Eighteen additional isolates required CO2, and did not grow in Oxyrase. With the exception of fusobacteria, with which azithromycin yielded the lowest MICs, clarithromycin had the lowest MICs with both methods. These results show that the pH effect of incubation in CO2 can be avoided by using the Oxyrase method, or by incubating in CO2 with pH adjusted to 8.0. The latter method has the advantage of allowing testing of strains requiring CO2.

Anti-Bacterial Agents↗

Trovafloxacin compared with levofloxacin, ofloxacin, ciprofloxacin, azithromycin and clarithromycin against unusual aerobic and anaerobic human and animal bite-wound pathogens.

The activity of trovafloxacin and five other oral agents against 250 aerobic and 137 anaerobic strains isolated from human and animal bite wounds was determined by an agar dilution method. Trovafloxacin was active against all aerobic and fastidious facultative isolates at < or = 0.5 mg/L and all anaerobes at < or = 2 mg/L (Bacteroides tectum, Porphyromonas salivosa and Prevotella heparinolytica, < or = 0.25 mg/L; Porphyromonas spp., < or = 0.5 mg/L; Prevotella spp. and peptostreptococci, < or = 2.0 mg/L), except Fusobacterium nucleatum and other fusobacteria (MIC90 < or = 4 mg/L). Levofloxacin was generally one to two dilutions more active than ofloxacin, while ciprofloxacin was active against aerobes (MIC < or = 1 mg/L) but less active against anaerobic strains (MIC90 < or = 16 mg/L).

Animals↗

In vitro activity of R-95867, the active metabolite of a new oral carbapenem, CS-834, against anaerobic bacteria.

The in vitro activity of R-95867, the active metabolite of a new oral carbapenem, CS-834, was compared with those of DU-6859a, cefditoren, ampicillin/sulbactam and clindamycin against a variety of anaerobic bacteria. R-95867 inhibited 90% of anaerobic strains at </=2 mg/L. In general, R-95867 was 2- to 4-fold less active than DU-6859a but more active than other agents tested against strains of peptostreptococci, clostridia, the Bacteroides fragilis group, Porphyromonas spp. and fusobacteria. R-95867 was stable to hydrolysis by beta-lactamase type 2e derived from B. fragilis, Prevotella bivia and Prevotella intermedia, but unstable to hydrolysis by carbapenemase from B. fragilis.

Bacteria, Anaerobic↗

Synergic activity, for anaerobes, of trovafloxacin with clindamycin or metronidazole: chequerboard and time-kill methods.

Chequerboard titrations were used to test the activity of trovafloxacin, alone and in combination with clindamycin or metronidazole, against 156 Gram-positive or Gram-negative anaerobes, including 47 Bacteroides fragilis group, 36 Prevotella spp., 26 fusobacteria, 21 peptostreptococci and 26 clostridia. MIC50/MIC90 values (mg/L) of each drug alone against all 156 strains were: trovafloxacin, 0.5/1; clindamycin, 0.25/2; metronidazole, 1/2. Synergy (FIC indices </= 0.5) was seen in two strains with trovafloxacin plus clindamycin, and seven with trovafloxacin plus metronidazole. All other combinations were additive (FIC indices >0. 5-2.0); no antagonism (FIC indices >4.0) was seen. In addition, synergy was tested by time-kill methodology for each of the above combinations against 12 Gram-positive or Gram-negative strains. Results indicated that synergy (defined as a >/= 2 log(10) decrease in cfu/mL at 48 h compared with the more active drug alone) was found between trovafloxacin at or below the MIC and both clindamycin and metronidazole at or below the MIC in one strain each of Bacteroides fragilis, Bacteroides thetaiotaomicron, Prevotella intermedia, Fusobacterium varium, Peptostreptococcus asaccharolyticus and Clostridium bifermentans. Synergy between trovafloxacin (</=MIC) and metronidazole alone was seen in one strain each of Bacteroides distasonis, Prevotella bivia, Fusobacterium mortiferum, P. asaccharolyticus and C. bifermentans. In many cases of synergy, including those at the trovafloxacin MIC, regrowth after 48 h, which was commonly seen with trovafloxacin alone, was inhibited, and 99.9% killing was observed with the combination after 48 h, but not with trovafloxacin alone.

Anti-Bacterial Agents↗

Comparative in vitro activity of gemifloxacin.

Gemifloxacin is a new quinolone and, like moxifloxacin, trovafloxacin, grepafloxacin and clinafloxacin, is more potent in vitro than ciprofloxacin or ofloxacin against Gram-positive aerobes. Gemifloxacin was the most potent of the quinolones tested against streptococci and most ciprofloxacin-resistant pneumococci were susceptible to gemifloxacin. Gemifloxacin, like moxifloxacin, trovafloxacin, grepafloxacin and clinafloxacin, was more potent than ciprofloxacin or ofloxacin against all staphylococci and many ciprofloxacin-resistant isolates were susceptible to these quinolones. Against Gram-negative aerobes gemifloxacin was as potent as or slightly less potent than ciprofloxacin, and isolates resistant to ciprofloxacin were also resistant to gemifloxacin and to moxifloxacin, trovafloxacin and grepafloxacin. Gemifloxacin was also the most potent quinolone against Gram-positive anaerobes and fusobacteria but trovafloxacin was the most potent agent tested against other Gram-negative anaerobes.

Anti-Infective Agents↗