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Antimicrobial susceptibility of uncommonly isolated non-enteric Gram-negative bacilli.

The frequency of occurrence and antimicrobial susceptibility patterns of 3059 non-enteric Gram-negative bacilli (NGB), other than Pseudomonas aeruginosa and Acinetobacter spp., consecutively collected as part of the SENTRY Antimicrobial Surveillance Program (1997-2003) were reviewed. During this period, a total of 221,084 bacterial isolates were collected from several clinical specimens worldwide, including 25,305 (11.5%) NGB. Acinetobacter spp. and P. aeruginosa accounted for 82.7% of the NGB isolates and have been excluded from this analysis. The antimicrobial susceptibility results of 3509 strains from 13 species/genera have been analysed in this review. The isolates were tested by reference broth microdilution methods in three central laboratories using common reagents and procedures. More than 30 antimicrobial agents were tested and the results for the 18 most active compounds are reported here. Stenotrophomonas maltophilia (2076 strains; 59.2%) was the most frequently isolated pathogen in this group, followed by Aeromonas spp. (385 strain; 11.0%), Burkholderia cepacia (269 strains; 7.7%), Pseudomonas fluorescens/putida (253 strains; 7.2%) and Alcaligenes spp. (236 strains; 6.7%). All other species/genera accounted for less than 3% of the isolates analysed. The antimicrobial agents with the most consistent activity against the NGB evaluated in the present study were the newer fluoroquinolones gatifloxacin and levofloxacin with 84.1 and 84.9% susceptibility overall. Trimethoprim/sulphamethoxazole was active against 85.3% of the isolates tested, but showed reduced activity against P. fluorescens/putida (22.1% susceptibility). Antimicrobial susceptibility varied significantly between species/genera and the geographical regions evaluated. Thus, proper identification and quantitative susceptibility testing will be required for the treatment of NGB infections. Extensive worldwide surveillance programmes remain extremely important to guide empirical antimicrobial therapy for rarely isolated pathogens and also for pathogens that are not routinely tested due to the lack of standardised susceptibility testing methods.

Anti-Bacterial Agents↗

Cefetamet pivoxil in acute pyelonephritis: an open study.

Fifty-five adult patients with acute uncomplicated pyelonephritis were investigated in an open, prospective, randomized comparative study in which 31 patients were allocated to receive 1000 mg cefetamet pivoxil twice daily (or 2000 mg once daily) and 24 to receive 1000 mg cefadroxil twice daily, given orally for 10 to 15 days. Both groups were comparable for age, sex and body weight. Clinical signs and symptoms, i.e. flank tenderness, dysuria, urgency and pyuria, subsided somewhat more rapidly with cefetamet pivoxil, while defervescence was obtained by Day 3 +/- 1 in both groups. Twenty-nine of the cefetamet pivoxil patients were assessed bacteriologically. The pathogens isolated prior to treatment were E. coli (22), Proteus mirabilis (5), P. vulgaris (1) and P. stuartii (1). All 29 patients had sterile urine at treatment end. In the 22 assessable patients in the cefadroxil group, the pathogens isolated before treatment were E. coli (17), P. mirabilis (3), and K. pneumoniae (2). Six patients had relapsed at treatment end (5 E. coli and 1 P. mirabilis). Patients were re-assessed at follow-up, usually 2 to 4 weeks after the end of treatment. Four of the 29 patients in the cefetamet pivoxil group showed relapse (3 E. coli and 1 P. mirabilis) as did a further 3 in the cefadroxil group (2 E. coli and 1 P. mirabilis). The overall therapeutic outcome was considered as successful, i.e. cure or improvement, in 89.7% of the cefetamet pivoxil patients and 72.7% of those who had received cefadroxil. Tolerability was satisfactory for both trial drugs and there were only a few mild to moderately severe adverse events reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

An epidemiological profile and trend analysis of wound flora in burned children: 7 years' experience.

A retrospective chart review was conducted of 5418 culture and sensitivity reports from 93 paediatric burn patients to determine profiles of wound flora and invasive organisms, trend analysis and patterns of antibiotic resistance. Coagulase-positive Staphylococcus was the predominant burn wound pathogenic isolate and the predominant invasive organism for burns less than 60 per cent BSA. Pseudomonads were the predominant invasive organism for burn wounds greater than or equal to 60 per cent BSA. Only 7 per cent of all pathogenic isolates were fungi. A significant association was demonstrated between increasing burn size and an increasing incidence of Gram-negative and invasive organisms. Silver sulphadiazine remains a very effective topical agent for the control of bacterial and fungal growth in burn wounds after 10 years of intensive use in this burn unit. Pseudomonad isolates were routinely multi-drug resistant. Pseudomonad isolates from wounds treated topically with a silver sulphadiazine-cerium nitrate mixture were frequently resistant to aminoglycosides, colistin and carbenicillin. It is concluded from this review that severe restrictions on antibiotic usage within burn units, and strict internal environmental control within burn units may help to decrease the incidence of nosocomial resistant strains and cross infection. Regular monitoring of burn wound flora, and the protocol for wound care used in treating these patients have been effective in preventing septic episodes and death due to sepsis.

Bacteria↗

[Epidemiology of nosocomial infections in pediatrics].

The overall incidence of nosocomial infections (NI) in pediatrics ranges between 2.3% to 12.6%. They have great variations according to age (7-12% under 1 year of age vs 1.5-4% after ten years of age), and the nature of the unit (3-26% in intensive care units vs 1-4% in general pediatrics). The main sites of infection are in children gastrointestinal infections (10-35% of NI) and bacteremia (10-23% of NI) whereas in adults urinary tract infections (31.7 to 35%) and respiratory infections (19 to 25%) are the most frequent. Viruses represent 22-27% of the isolated pathogens, and Gram positive cocci 31-50% (half of them are coagulase negative staphylococci). The most frequent Gram negative bacilli are Pseudomonas aeruginosa (9-15%), E. coli (6-16%) and Klebsiella pneumoniae (3-5%). Candida represent 3% of isolated pathogens in NI. The proportion of methicilline-resistant Staphylococcus aureus is lower in children than in adults. The prevalence of methicillin resistance of CNS is however close to that observed in adults, as is the multiresistance of Gram negative bacilli (Klebsiella). Candida infections seem an emerging problem in paediatrics. These results underline the necessity to limit the antimicrobial therapy in children as in adults.

Bacteremia↗

Multi-resistance to antimicrobial agents for the ten most frequently isolated bacterial pathogens.

Cross-resistance and multi-resistance to selected antibiotics was determined for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Amikacin-resistant Enterobacteriaceae often showed cross-resistance to ss-lactam antibiotics. Only 1% of the Escherichia coli isolates showed resistance to more than four antibiotics from a set of seven. This rate was higher for other Enterobacteriaceae and there were high levels of cross-resistance for P. aeruginosa. The cross-resistance of oxacillin with other antibiotics is well known in staphylococci. Penicillin-resistant pneumococcal isolates were cross-resistant to macrolides. Cross-resistance was only a minor problem in H. influenzae and M. catarrhalis. Cross- and multi-resistance are important problems for Gram-negative and Gram-positive bacteria but not for fastidious bacteria with the exception of penicillin-resistant S. pneumoniae.

Anti-Bacterial Agents↗

Bacteremia and antimicrobial susceptibilities in HIV-infected patients at Siriraj Hospital.

Bacterial infections in human immunodeficiency virus (HIV) infected patients may frequently develop into septicemia. Our study evaluated the bacterial pathogens isolated from hemocultures of HIV-infected patients at Siriraj Hospital and their antimicrobial susceptibility tests. The percentages of positive hemocultures were 24.64, 21.38, 23.88, and 28.46% in 1996, 1997, 1998, and 1999, respectively. Salmonella spp was the most pathogen isolated, followed by Escherichia coil (10.93%), Staphylococcus aureus (8.2%), coagulase-negative staphylococci (6.56%), nonfermentative gram-negative rods (6.01%), Pseudomonas aeruginosa (5.46%), Klebsiella pneumoniae (4.37%), and Enterobacter spp (4.37%). Salmonella, serogroup C was the most frequently isolated serogroup. It was sensitive to amoxicillin/clavulanate in 100%, ampicillin/sulbactam in 89%, cefazolin, cefuroxime, cefotaxime, ceftriaxone, ceftazidime, imipenem, gentamicin, amikacin, netilmycin, ofloxacin, and ciprofloxacin in 100%. The changing spectrum of bacteria and antimicrobial susceptibility patterns in HIV-1 infected patients may provide a guideline for the selection of appropriate drugs for treatment.

AIDS-Related Opportunistic Infections↗

Antibiograms of pathogenic bacteria isolated from laboratory animals.

Study of antibiotic sensitivity patterns of 178 bacterial isolants from laboratory animals revealed that these bacteria in general were sensitive to many commonly used antibiotics; however, there were notable exceptions. This report presents current antibiotic sensitivity patterns of most gram-negative and gram-positive bacterial pathogens common to laboratory animals.

Ampicillin↗

Timentin in the treatment of symptomatic complicated urinary tract infections in adult patients.

The safety and effectiveness of Timentin were evaluated in 34 adult patients with symptomatic complicated urinary tract infections, principally due to multiply-drug-resistant bacteria. Although a wide variety of organisms, particularly gram-negative bacilli, were found, Escherichia coli was the most frequent, accounting for 14 of 45 (31 percent) pathogens isolated. Ten (22 percent) isolates were Pseudomonas aeruginosa; 11 (24 percent) were Proteus or Morganella species; three (7 percent) were Citrobacter; one (2 percent) was Klebsiella pneumoniae; two (4 percent) were Staphylococcus aureus; and two (4 percent) were enterococci. Ninety-three percent of all pathogens isolated produced a beta-lactamase. Eight (24 percent) infections were polymicrobial; seven (21 percent) were associated with bacteremia. Clinical improvement occurred in 30 of 34 (86 percent) patients. All bacteremias were cured. Although bacteriologic cure occurred in only 32 percent of patients, control of sepsis and temporary eradication of bacteria (bacteriologic improvement) occurred in 96 percent. Not surprisingly, the rates of relapses and reinfections were high. It was concluded that Timentin is a useful agent in the management of complicated urinary tract infection and offers clinicians an alternative to more toxic antibiotics, such as aminoglycosides.

Adult↗

Imferon agar: improved medium for isolation of pathogenic Neisseria.

Imferon, an iron-dextran complex, enhances the growth of Neisseria gonorrhoeae and N. meningitidis. The use of Imferon as a replacement for ferric nitrate, in a defined supplement for GC agar significantly increased the average colony sizes of both gonococci and meningococci. In comparison with Thayer-Martin medium, Imferon agar increased the speed and rate of isolation of gonococci from clinical specimens.

Agar↗

Double-blind, randomized study of the efficacy and safety of oral pharmacokinetically enhanced amoxicillin-clavulanate (2,000/125 milligrams) versus those of amoxicillin-clavulanate (875/125 milligrams), both given twice daily for 7 days, in treatment of bacterial community-acquired pneumonia in adults.

This randomized, double-blind, noninferiority trial was designed to demonstrate that pharmacokinetically enhanced amoxicillin-clavulanate (2,000/125 mg) was at least as effective clinically as amoxicillin-clavulanate 875/125 mg, both given twice daily for 7 days, in the treatment of community-acquired pneumonia in adults. In total, 633 clinically and radiologically confirmed community-acquired pneumonia patients (intent-to-treat population) were randomized to receive either oral amoxicillin-clavulanate 2,000/125 mg (n = 322) or oral amoxicillin-clavulanate 875/125 mg (n = 311). At screening, 160 of 633 (25.3%) patients had at least one typical pathogen isolated from expectorated or invasive sputum samples or blood culture (bacteriology intent-to-treat population). Streptococcus pneumoniae (58 of 160, 36.3%), methicillin-susceptible Staphylococcus aureus (34 of 160, 21.3%), and Haemophilus influenzae (33 of 160, 20.6%) were the most common typical causative pathogens isolated in both groups in the bacteriology intent-to-treat population. Clinical success in the clinical per protocol population at test of cure (days 16 to 37), the primary efficacy endpoint, was 90.3% (223 of 247) for amoxicillin-clavulanate 2,000/125 mg and 87.6% (198 of 226) for amoxicillin-clavulanate 875/125 mg (treatment difference, 2.7; 95% confidence interval, -3.0, 8.3). Bacteriological success at test of cure in the bacteriology per protocol population was 86.6% (58 of 67) for amoxicillin-clavulanate 2,000/125 mg and 78.4% (40 of 51) for amoxicillin-clavulanate 875/125 mg (treatment difference, 8.1%; 95% confidence interval, -5.8, 22.1). Both therapies were well tolerated. Amoxicillin-clavulanate 2,000/125 mg twice daily was shown to be as clinically effective as amoxicillin-clavulanate 875/125 mg twice daily for 7 days in the treatment of adult patients with community-acquired pneumonia, without a noted increase in the reported rate of adverse events.

Adolescent↗

Longitudinal analysis of CD8(+) T-cell phenotype and IL-7, IL-15 and IL-16 mRNA expression in different tissues during primary simian immunodeficiency virus infection.

Infection of macaques with pathogenic isolates of simian immunodeficiency virus (SIV) represents a useful model of HIV infection that offers the unique opportunity to investigate the very early modifications that affect CD8(+) T-lymphocyte subsets and related cytokines during lentiviral infection. Herein, three cynomolgus macaques were inoculated intravenously with a pathogenic isolate of SIVmac 251. In fresh isolated mononuclear cells from blood, lymph node and bronchoalveolar lavage, we analyzed changes in the phenotype of CD8(+) T cells and we used reverse transcription-PCR to monitor the expression of IL-7, IL-15 and IL-16 mRNA. We demonstrated that an expansion of CD8(+)CD28(-) T cells occurs from the third week of infection on in the peripheral blood and in the lung, whereas CD8(+)CD28(+) T cells expand in the lymph nodes. Concomitantly, we evidenced mRNA modulations in IL-16, IL-15 and IL-7 expression in the three compartments studied. The containment of systemic viral replication was associated with an overexpression of IL-16 mRNA in the lung and in the peripheral blood. Given the immunomodulatory properties of IL-15 and IL-7 and the potential antiviral ability of IL-16, these perturbations could have important implications in early viral dissemination and HIV immunopathogenesis.

Animals↗

A new therapeutic option for the treatment of pneumonia.

Patients with bacterial pneumonia often are treated empirically with parenteral broad-spectrum antimicrobials intended to cover potential gram-negative and gram-positive pathogens. However, beta-lactamase-mediated resistance has developed to many of these antimicrobials, particularly third-generation cephalosporins, and has led to the development of fourth-generation agents that are relatively beta-lactamase stable. The purpose of these studies was to compare the efficacy and safety of the fourth-generation agent, cefepime, with that of the third-generation agent, ceftazidime, in the treatment of hospitalized patients with moderate-to-severe bacterial pneumonia. A total of 336 (97 evaluable) patients were enrolled in an open-label study, and 99 (23 evaluable) patients were enrolled in a blinded study of patients with lower respiratory tract infections (LRTI) including pneumonia. Patients were randomized to receive either cefepime 1 g every 12 hours or ceftazidime 1 g every 8 hours given as an intravenous infusion over 30 minutes. Efficacy analysis included the evaluable patients while the safety analysis included all patients. The results in the open-label study were as follows: In patients with pneumonia, clinical response was satisfactory in 58 (85%) of 68 patients in the cefepime group and 21 (72%) of 29 patients in the ceftazidime group. Bacteriologic eradication occurred for 75 (93%) of 81 pathogens and 30 (94%) of 32 pathogens isolated from the 68 cefepime-treated patients and 29 ceftazidime-treated patients, respectively. The results in the blinded study were as follows: In patients with pneumonia, clinical response was satisfactory in 12 (80%) of 15 cefepime patients and in 7 (88%) of 8 ceftazidime patients, and the bacteriologic eradication rates were 85% (17/20 pathogens) and 73% (8/11 pathogens) isolated from the 15 cefepime-treated patients and the eight ceftazidime-treated patients, respectively. Among the most frequent adverse events in both groups were nausea, diarrhea, vomiting, and abdominal pain. Similar adverse events were noted in the 99 patients in the blinded study. These studies indicate that the efficacy and safety of cefepime administered at 1 g twice daily is comparable to that of ceftazidime administered at 1 g three times daily for treatment of hospitalized patients with pneumonia caused by susceptible pathogens.

Acute Disease↗

Inapparent outbreaks of ventilator-associated pneumonia: an ecologic analysis of prevention and cohort studies.

OBJECTIVE: To compare ventilator-associated pneumonia (VAP) rates and patterns of isolates across studies of antibiotic and non-antibiotic methods for preventing VAP. DESIGN: With the use of 42 cohort study groups as the reference standard, the prevalence of VAP was modeled in two linear regressions: one with the control groups and the other with the intervention groups of 96 VAP prevention studies. The proportion of patients admitted with trauma and the VAP diagnostic criteria were used as ecologic correlates. Also, the patterns of pathogenic isolates were available for 117 groups. RESULTS: In the first regression model, the VAP rates for the control groups of antibiotic-based prevention studies were at least 18 (CI95, 12 to 24) per 100 patients higher than those in the cohort study groups (P < .001). By contrast, comparisons of cohort study groups with all other control and intervention groups in the first and second regression models yielded differences that were less than 6 per 100 and not significant (P > .05). For control groups with VAP rates greater than 35%, the patterns of VAP isolates, such as the proportion of Staphylococcus aureus, more closely resembled those in the corresponding intervention groups than in the cohort groups. CONCLUSIONS: The rates of VAP in the control groups of the antibiotic prevention studies were significantly higher than expected and the patterns of pathogenic isolates were unusual. These observations suggest that inapparent outbreaks of VAP occurred in these studies. The possibility remains that antibiotic-based VAP prevention presents a major cross-infection hazard.

Anti-Bacterial Agents↗

Molecular analysis of mutS expression and mutation in natural isolates of pathogenic Escherichia coli.

Deficiencies in the MutS protein disrupt methyl-directed mismatch repair (MMR), generating a mutator phenotype typified by high mutation rates and promiscuous recombination. How such deficiencies might arise in the natural environment was determined by analysing pathogenic strains of Escherichia coli. Quantitative Western immunoblotting showed that the amount of MutS in a wild-type strain of the enterohaemorrhagic pathogen E. coli O157 : H7 decreased about 26-fold in stationary-phase cells as compared with the amount present during exponential-phase growth. The depletion of MutS in O157 : H7 is significantly greater than that observed for a laboratory-attenuated E. coli K-12 strain. In the case of stable mutators, mutS defects in strains identified among natural isolates were analysed, including two E. coli O157 : H7 strains, a diarrhoeagenic E. coli O55 : H7 strain, and a uropathogenic strain from the E. coli reference (ECOR) collection. No MutS could be detected in the four strains by Western immunoblot analyses. RNase T2 protection assays showed that the strains were either deficient in mutS transcripts or produced transcripts truncated at the 3' end. Nucleotide sequence analysis revealed extensive deletions in the mutS region of three strains, ranging from 7.5 to 17.3 kb relative to E. coli K-12 sequence, while the ECOR mutator contained a premature stop codon in addition to other nucleotide changes in the mutS coding sequence. These results provide insights into the status of the mutS gene and its product in pathogenic strains of E. coli.

Adenosine Triphosphatases↗

Isolation of pathogenic Legionella species and legionella-laden amoebae in dental unit waterlines.

Legionella released into the air during treatment are a potential source of infection. Water stagnation in dental unit waterlines (DUWLs) creates biofilms and promotes the proliferation of these micro-organisms. This study investigated the presence of amoeba infected with legionella, L. pneumophila and other pathogenic Legionella species in a dental teaching hospital. Water samples were collected in the morning and afternoon from 99 dental units and 16 taps connected to the municipal water supply. Samples were plated on selective media and tested for legionella using the direct immunofluorescent antibody technique and the latex agglutination test. Legionella were found in 33% of the DUWLs and in 47% of the mains taps supplying these units. Legionella-laden amoebae occurred in one mains tap sample and in 20% of DUWLs in a clinic of the teaching hospital. L. micdadei was the predominant species isolated from this clinic. L. pneumophila serogroups 2-14 predominated in the mains water, whereas L. pneumophila serogroup 1 was found in approximately half of the contaminated DUWLs and mains taps irrespective of the time of sampling. Pathogenic Legionella species seeded by municipal water into DUWLs is a potential source of legionella infection for both dental personnel and patients during prolonged dental treatment. This problem is compounded by the presence of legionella-laden amoebae which may contain levels of organism well within the infective dose. The interaction of legionella with amoebae is an important ecological factor that may significantly increase the risk of legionellosis, and thus should be given further consideration in the refinement of risk assessment models.

Amoeba↗

Small bowel and fecal microbiology in children suffering from persistent diarrhea in Bangladesh.

BACKGROUND: The etiology of persistent diarrhea in children is multifactorial. The objective of the current study was to ascertain the role of microorganisms in the etiology and pathogenesis of persistent diarrhea in a group of children in Bangladesh. METHODS: Enteric pathogens and total aerobic microflora were studied in the duodenal aspirates of 100 children with persistent diarrhea and compared with those in aspirates of 30 children with acute diarrhea, and those in aspirates of 15 healthy control children. The enteric pathogens in the stools of these children and in stools of an additional 38 patients with persistent diarrhea and 12 with acute diarrhea were also studied. RESULTS: Approximately two thirds of the patients with acute diarrhea and persistent diarrhea, and half of the control subjects had more than 10(5) organisms per milliliter of duodenal fluid. Significantly, more patients with persistent diarrhea had a greater variety of flora than did patients with acute diarrhea and control subjects. The predominant organisms in patients with acute diarrhea and in those with persistent diarrhea were Gram-negative rods, whereas those in control subjects were Gram-positive cocci. Significantly more acute diarrhea patients and persistent diarrhea patients had enteric pathogens isolated from stool than did control subjects. Diarrheagenic Escherichia coli, as a whole, were present in significantly more persistent diarrhea patients than in acute diarrhea patients and control subjects. Among diarrheagenic E. coli, enteroaggregative E. coli were significantly associated only with persistent diarrhea. Other organisms significantly associated with persistent diarrhea were Aeromonas spp. and Klebsiella spp. Some patients in the acute diarrhea and the persistent diarrhea groups had the same pathogens isolated from both the duodenal fluid and stool. CONCLUSIONS: In accordance with results of other studies, an association between enteroaggregative E. coli and persistent diarrhea was found in the present study. This suggests that therapy directed against enteroaggregative E. coli can be evaluated for management of some cases of persistent diarrhea.

Acute Disease↗

Streptomyces luridiscabiei sp. nov., Streptomyces puniciscabiei sp. nov. and Streptomyces niveiscabiei sp. nov., which cause potato common scab disease in Korea.

Three plant-pathogenic isolates of Streptomyces spp., isolated from potatoes with common scab disease lesions in Korea, are described as novel species. Morphological and physiological properties of these isolates were distinct from those of previously described Streptomyces species. Strain S63(T) has yellow-white, smooth, cylindrical spores that are borne in monoverticillus flexuous spore-chains. Strain S77(T) has purple-red, spiny spores that are borne in simple rectus flexuous spore-chains. Strain S78(T) has white, smooth, cylindrical spores that are borne in simple rectus flexuous spore-chains. These three isolates differed from known pathogenic strains by analysis of 16S rRNA gene sequences in a previous study. Furthermore, genetic uniqueness of our isolates was confirmed by sequencing of the 16S-23S internal transcribed spacer (ITS) region, which indicated that isolates S63(T) and S78(T) belong to the genus Streptomyces and have low homology to other Streptomyces species (less than 71.2 and 75.7 %, respectively). The 16S-23S ITS region of strain S77(T) was not amplified by these primer sets. DNA-DNA hybridization results for all three isolates show distant relationships to previously described Streptomyces species; therefore, on the basis of polyphasic evidence, the names Streptomyces luridiscabiei sp. nov. for strain S63(T) (=LMG 21390(T)=KACC 20252(T)), Streptomyces puniciscabiei sp. nov. for strain S77(T) (=LMG 21391(T)=KACC 20253(T)) and Streptomyces niveiscabiei sp. nov. for strain S78(T) (=LMG 21392(T)=KACC 20254(T)) are proposed.

Base Sequence↗