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Coagulase-negative staphylococcal meningitis in adults: clinical characteristics and therapeutic outcomes.

BACKGROUND: We wanted to analyze the clinical characteristics and therapeutic outcomes of adult meningitis caused by coagulase-negative staphylococci (CoNS). PATIENTS AND METHODS: Over a period of 5 years (January 1999 to December 2003), 127 cases were identified as having adult culture-proven bacterial meningitis caused by a single pathogen. Of them, 14 cases with CoNS meningitis were enrolled, and their clinical characteristics and therapeutic outcomes were analyzed. RESULTS: The 14 cases (median age 37.5; range 24-77 years old) included nine men and five women. With polynerase chain reaction sequencing of bacterial 16S r-RNA, 10 of the 14 CoNS strains were identified as Staphylococcus epidermidis infection, and the other four belonged to Staphylococcus haemolyticus. All 14 cases were in a postneurosurgical state with insertion of a ventriculoperitoneal shunt, external ventricular device or intrathecal port A as their underlying conditions, and 12 of the 14 patients contracted the infection nosocomially. Fever (86%), leukocytosis (79%), hydrocephalus (50%), consciousness disturbance (36%), and seizure (7%) were the major clinical manifestations. All the involved CoNS strains showed resistance to oxacillin but retained their susceptibility to vancomycin and linezolid. All 14 CoNS strains had positive mecA gene detection. With the removal of neurosurgical devices and intravenous vancomycin therapy, 86% (12/14) of the patients survived. CONCLUSION: CoNS meningitis accounted for 11% (14/127) of our adult bacterial meningitis. All adult CoNS meningitis patients had a disrupted barrier of the central nervous system as the underlying condition. S. epidermidis was the most common CoNS subtype involved. All involved CoNS strains were oxacillin resistant. The therapeutic result showed that adult CoNS meningitis had a mortality rate of 14% (2/14).

Acetamides↗

Mixed infection in adult bacterial meningitis.

12 adult patients suffering from bacterial meningitis caused by mixed infection were identified at Kaohsiung Chang Gung Memorial Hospital over a period of 13 years (1986-1998), and they accounted for 6.5% (12/184) of our culture-proven adult bacterial meningitis. The 12 cases included seven males and five females, aged 17-74 years. Six of the 12 cases had community-acquired infections and the other six had nosocomially-acquired infections. Ten of the 12 cases had associated underlying diseases, with head trauma and/or neurosurgical procedure being the most frequent. Both gram-negative and gram-positive pathogens were identified in these 12 cases with gram-negative pathogens outnumbering the gram-positive ones. The implicated pathogens, starting with the most frequent, included Enterobacter species (Enterobacter cloacae, Enterobacter aerogenes), Klebsiella species (Klebsiella pneumoniae, Klebsiella oxytoca), Escherichia coli, Staphylococcus species (Staphylococcus aureus, Staphylococcus haemolyticus), Pseudomonas aeruginosa, Acinetobacter baumannii, Enterococcus, Serratia marcescens, Citrobacter diversus, Proteus mirabilis, Streptococcus viridans and Neisseria meningitidis. Six of the 12 cases were found to have multi-antibiotic-resistant strains, which included E. cloacae in one, A. baumannii in one, K. pneumoniae in one and S. aureus in three. The management of these 12 cases included appropriate antibiotics and neurosurgical procedures including shunt revision. Despite the complexity of implicated pathogens and the high incidence of emergence of resistant strains, the overall mortality rate (8.3%, 1/12) was not higher than that in adult bacterial meningitis. However, complete recuperation was difficult in adult patients with mixed bacterial meningitis.

Adolescent↗

Value of the L-pyrrolidonyl-beta-naphthylamide hydrolysis test for identification of select gram-positive cocci.

A 4 hr test for hydrolysis of L-pyrrolidonyl-beta-naphthylamide (PYR) was evaluated for its use in identifying group A beta-hemolytic streptococci, group D enterococci, and Staphylococcus haemolyticus. All of the group A streptococci and the enterococci tested were positive in the PYR test, whereas all of the nongroup A, B, or D beta-hemolytic streptococci, all of the viridans, and all of the Streptococcus pneumoniae isolates tested were PYR negative. Two strains of Aerococcus species were PYR positive and could not be differentiated from enterococci in this test. All strains of S. haemolyticus, a single strain of S. intermedius and two of seven strains of S. warneri were PYR positive whereas all other staphylococci tested were PYR negative. The PYR test is suitable for routine, presumptive identification of group A streptococci, group D enterococci and S. haemolyticus in the clinical laboratory.

Humans↗

In vitro activity of mersacidin (M87-1551), an investigational peptide antibiotic tested against gram-positive bloodstream isolates.

We measured the in vitro activity of mersacidin (formerly M87-1551) against 183 clinical isolates (vancomycin susceptible) and 12 additional vancomycin-resistant strains of Gram-positive bacteria. The activity for mersacidin increased an average twofold (range, 1.7- to 7.6-fold) in a calcium-enriched medium. The minimum inhibitory concentration (MIC)90 for mersacidin was 8-32 times higher than vancomycin for staphylococci, 4-64 times higher for enterococci, and up to 32 times higher for other organisms tested. The MIC90 for MDL 62873, a comparison compound, was less than or equal to 0.5 micrograms/ml for all species except Staphylococcus haemolyticus (MIC90, 4 micrograms/ml), and it was greater than or equal to 4-fold more active than vancomycin. Against selected vancomycin-resistant strains, mersacidin had MICs greater than or equal to 16 micrograms/ml for enterococci, 4-32 micrograms/ml for Pediococcus, and less than or equal to 2 micrograms/ml for Leuconostoc species. Mersacidin may have some clinical utility in documented infections caused by staphylococci, nonenteric streptococci, Pediococcus, and Leuconostoc.

Anti-Bacterial Agents↗

Antimicrobial activity of cefpirome. An update compared to five third-generation cephalosporins against nearly 6000 recent clinical isolates from five medical centers.

Cefpirome, cefotaxime, ceftazidime, cefoperazone, ceftizoxime, and ceftriaxone were tested against approximately 6000 fresh clinical isolates from five medical centers. For 3031 strains of Enterobacteriaceae tested, cefpirome consistently had the lowest MIC50s and lowest percentage of resistant strains. Cefpirome was also the most active agent against the 2138 Gram-positive cocci tested; Staphylococcus haemolyticus was uniformly resistant to all agents tested. Against 791 nonenteric Gram-negative bacilli, the activity of cefpirome was most comparable to that of cefoperazone and slightly less active than ceftazidime. Among the current third-generation cephalosporins, cefotaxime and cefoperazone emerged as having better overall balanced activity. Ceftazidime displayed poorest coverage against Enterobacteriaceae and Gram-positive organisms. Ceftizoxime also provided compromised coverage of staphylococci and nonenteric Gram-negative bacilli. Cefpirome remains as active as originally described in 1984 and possesses a slightly wider spectrum of activity against contemporary aerobic pathogens compared to currently marketed third-generation cephalosporins.

Bacteria↗

Cell wall deficient bacteria as a cause of idiopathic hematuria.

Idiopathic hematuria in the absence of bacteriuria is a medical challenge. Routine cultures of catheterized bladder and endoscopically obtained ureteral urine specimens from a 22-year-old woman with a 6-week history of hematuria showed no growth after 24 to 48 hours of incubation. However, bacterial variants were grown on enriched media. Colonies were typical cell wall deficient/defective bacteria. Phase and electron microscopy of cystoscopic urine specimens obtained by retrograde ureteral catheterization as well as phase microscopy of the cultures revealed the classic morphology of these organisms. When the variant cultures were subcultured the organisms reverted to their related walled forms, that is Streptococcus agalactiae and Staphylococcus haemolyticus. Because the colonies of these organisms showed various patterns of biochemical reactivity, each phenotype was tested against 15 antimicrobials. Collectively, all biotypes had a common susceptibility to only nitrofurantoin. The patient was treated with nitrofurantoin for 6 weeks. Four days after initiation of therapy she had complete remission of hematuria. During the next 3 years she remained well and free of hematuria.

Adult↗

Inverse paradoxical embolism in a patient on chronic hemodialysis with aortic bacterial endocarditis.

We present a 45-year-old patient on chronic hemodialysis who suffered aortic endocarditis by Staphylococcus haemolyticus after bacteremia associated with a venous catheter, which was used temporarily during the maturing phase of a Cimino-Brescia arteriovenous fistula in the left forearm. Three weeks after starting antibiotic therapy, the patient suffered a septic pulmonary embolism. The catheter had been removed 4 weeks before the embolism. Thrombophlebitis of lower limbs, infection or thrombosis of the vascular access, and the involvement of right-sided cardiac structures were all discarded. We assumed that the pulmonary episode was probably a consequence of the paradoxical passage of embolic material, detached from the aortic valve, from arterial to venous circulation through the arteriovenous fistula.

Aortic Valve↗

Effect of oral administration of a variety of bacteria on depressed macrophage functions in tumour-bearing rats.

In consideration of the well documented influence of normal microbial flora on the level of activation of macrophages, we evaluated the effects of oral administration of bacteria on rats with depressed macrophage functions. An oral, killed polyvalent vaccine (Diplococcus pneumoniae types I, II and III, Streptococcus haemolyticus, Staphylococcus aureus and Haemophilus influenzae), the live lyophilized Streptococcus faecium and spores of Bacillus subtilis, respectively, were administered orally to immuno-depressed rats. Results demonstrate the restoration of phagocytosis, intracellular killing and the chemotactic activity of macrophages. These experimental observations suggest that bacterial flora associated with mucosae can influence the level of activation of peritoneal macrophages.

Administration, Oral↗

Antimicrobial activity of imipenem against isolates from complicated urinary tract infections.

Antimicrobial activity of imipenem was measured using 4725 strains isolated from patients with complicated urinary tract infections (CUTIs) between 1988 and 2000. Imipenem was inactive against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, Enterococcus faecium and some non-fermenting Gram-negative rods. Resistant strains (MIC>16 mg/l) were observed in Staphylococcus haemolyticus (22%), Enterococcus faecalis (4%), Enterococcus avium (8%), Serratia marcescens (5%) and Pseudomonas aeruginosa (7%). Although the prevalence of imipenem-resistant strains of S. aureus, S. epidermidis and P. aeruginosa was sporadically high in some years, no steady increase was seen over the period. Resistant strains were rare in other major uropathogenic species. These results suggest that imipenem is still one of the most reliable antimicrobial drugs.

Anti-Bacterial Agents↗

Intrasellar abscess.

A case of intrasellar abscess in a 31-year-old male, with pituitary insufficiency, visual field and acuity disturbances, is reported. In the pus extracted at surgery E. coli and Staphylococcus haemolyticus were identified. The patient died 20 days after the operation. Necropsy revealed the fibrous capsule of an abscess in the hypophyseal region and putriform tissue at the level of the hypothalamus, with three small tumours one of which proved to be a craniopharyngioma.

Adult↗

Emergence of bacterial resistance to imipenem and ciprofloxacin in a university hospital.

We have continuously monitored the in-vitro activities of imipenem and ciprofloxacin against large numbers of non-fastidious clinical isolates. After eight years of use, 97-100% of Enterobacteriaceae and Acinetobacter baumannii remained susceptible to imipenem, but susceptibility of Pseudomonas aeruginosa declined from 100% to 91%. After six years of use, 94%-100% of Enterobacteriaceae (except Providencia stuartii) remained susceptible to ciprofloxacin but susceptibility of P. stuartii, A. baumannii and P. aeruginosa declined from 100% to 46%, 66% and 84%, respectively. Oxacillin-resistant staphylococci were considered to be resistant to imipenem and all beta-lactams. There were no quinolone-resistant staphylococci observed in 1986, but susceptibilities of Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus to ciprofloxacin decreased to 85-93% for oxacillin-susceptible strains and to 7-39% for oxacillin-resistant strains. Enterococcus faecalis has remained susceptible to imipenem and the modal MIC of ciprofloxacin has remained 1 mg/L; however, susceptibility to ciprofloxacin 2 mg/L decreased from 94% to 64%. Imipenem-quinolone cross-resistance was observed for staphylococci but not for P. aeruginosa.

Anti-Infective Agents↗

The in vitro activity of daptomycin against 514 Gram-positive aerobic clinical isolates.

The in vitro activity of daptomycin was assessed in comparison with that of vancomycin and penicillin against a wide range of Gram-positive aerobic clinical isolates. MICs were determined by an agar dilution method on Mueller-Hinton agar (NCCLS/EUCAST) and on Isotonic agar adjusted to contain 50 mg/L free calcium (BSAC). Both media were enriched with 5% horse blood for fastidious organisms. Daptomycin MICs for all 172 staphylococci, including methicillin-susceptible and methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus, were 0.03-0.5 mg/L. For 99 of the 100 enterococci (Enterococcus faecalis, n = 50; Enterococcus faecium, n = 50), including 37 vancomycin-resistant isolates, they were 0.25-2 mg/L. For all 108 beta-haemolytic streptococci, including Streptococcus pyogenes and Streptococcus agalactiae, daptomycin MICs were 0.016- 0.25 mg/L; for 101 alpha-haemolytic streptococci, including Streptococcus pneumoniae and 'viridans' streptococci, they were 0.016-2 mg/L. For miscellaneous vancomycin-resistant isolates including Lactobacillus spp., Lactococcus spp., Leuconostoc spp., Pediococcus spp. and isolates of Enterococcus casseliflavus and Enterococcus gallinarum, daptomycin MICs were 0.03-2 mg/L; MICs for the seven isolates of Listeria monocytogenes were 0.25-4 mg/L. There was little difference between the results on Mueller-Hinton agar and on supplemented Isotonic agar The discrepant results occasionally obtained tended to be one dilution higher on supplemented Isotonic agar. Daptomycin was active (MICs < or = 2 mg/L) against all the isolates tested with the exception of one isolate each of E. faecium and L. monocytogenes (MICs = 4 mg/L). Our results indicate that daptomycin MICs are independent of methicillin and vancomycin MICs.

Anti-Bacterial Agents↗

Cloning and expression of the glutamate racemase gene of Bacillus pumilus.

A glutamate racemase gene (murI) was found in Bacillus pumilus cells and cloned into Escherichia coli WM335, a D-glutamate auxotroph, by means of a genetic complement method. MurI of B. pumilus encodes a 272-amino acid protein with an unusual initiation codon, TTG. The deduced amino acid sequence shows significant similarity with those of glutamate racemases from E. coli (ratio of identical residues, 28%), Pediococcus pentosaceus (44%), and Staphylococcus haemolyticus (49%). B. pumilus MurI was expressed as a fusion protein connected to the N-terminal 12 residues of beta-galactosidase; the fusion protein showed glutamate racemase activity, and resembled the enzyme of P. pentosaceus in physicochemical and enzymological properties.

Amino Acid Isomerases↗

Microbiology of acute otitis externa.

OBJECTIVE: To isolate and characterize bacteria and fungi from acute otitis externa (AOE) and to obtain susceptibility profiles on each bacterial isolate. STUDY DESIGN: Prospective core series. METHODS: Specimens were collected from the external canals of subjects with clinically diagnosed acute otitis externa. Species-level identification for each bacterial isolate recovered was obtained by combining phenotypic and genotypic data. End point mean inhibitory concentration (MIC) testing was performed using National Committee for Clinical Laboratory Standards (NCCLS) recommended methods. RESULTS: In Alcon-sponsored clinical studies conducted in 1998 to 2000, microbiology specimens were collected from 2039 subjects (2240 diseased ears) by 101 investigators throughout the United States. A total of 2838 bacteria, 32 yeast, and 17 molds were recovered from 2048 ears clinically diagnosed as acute otitis externa. Of the 202 bacterial species recovered, the species most frequently isolated was Pseudomonas aeruginosa (38%). The next 10 species most frequently isolated were: Staphylococcus epidermidis, 9.1%; Staphylococcus aureus, 7.8%; Microbacterium otitidis, 6.6%; Microbacterium alconae, 2.9%; Staphylococcus caprae, 2.6%; Staphylococcus auricularis, 2.0%; Enterococcus faecalis, 1.9%; Enterobacter cloacae, 1.6%; Staphylococcus capitis subsp. Ureolyticus,1.4%; and Staphylococcus haemolyticus, 1.3%. Susceptibility profiles of S. epidermidis isolates revealed the greatest frequency of high-level resistance to selected antibiotics (>/=8 microg/mL): 23%, neomycin-resistant; 11%, oxacillin-resistant; and 12%, ofloxacin-resistant. Susceptibility profiles of S. aureus isolates revealed a lower frequency of high-level resistance: 6.3%, neomycin-resistant; 2.7%, oxacillin-resistant; and 4.5%, ofloxacin-resistant. P. aeruginosa with high-level resistance to quinolones (>/=128 mcg/mL for ofloxacin) was recovered from only 1 subject. Likewise, resistance of P. aeruginosa to aminoglycosides was rare. Twenty isolates had neomycin MICs >/=64 mcg/mL and 10 isolates had gentamicin MICs >/=16 mcg/mL. The coryneform isolates identified as Microbacterium otitidis had an intrinsic lack of susceptibility to quinolones (ofloxacin MICs >/=16 mcg/mL) and aminoglycosides (tobramycin MICs >/=32 mcg/mL and gentamicin MICs >/=8 mcg/mL). CONCLUSIONS: Bacterial infections of the external ear canal are most often caused by P. aeruginosa. However, there are a great number of other gram-positive and gram-negative bacterial species that are recovered from patients with acute otitis externa. Because of this diverse etiology, the best topical therapeutic choice for topical therapy is for the most potent, broad-spectrum (especially anti-P. aeruginosa) antibiotic available.

Acute Disease↗

Neonatal airway colonization with gram-negative bacilli: association with severity of bronchopulmonary dysplasia.

BACKGROUND: Airway colonization with Gram-negative bacilli (GNB) and Gram-positive cocci (GPC) is common in mechanically ventilated neonates. Whether GNB are related to nosocomial bloodstream infection (BSI) and/or to the severity of bronchopulmonary dysplasia (BPD) is unknown. METHODS: We prospectively examine this relationship using a cohort design. Data from 260 < or = 1250-g birth weight inborn infants (1991 to 1995) intubated > or = 2 weeks included 917 serial tracheal cultures and 583 blood cultures. The severity of BPD was assessed by duration of mechanical ventilation, oxygen dependency at 36 weeks of postconceptional age and the use of home oxygen supplementation. RESULTS: After 2 weeks of ventilation, 80% of the infants were colonized with GPC (Staphylococus epidermidis and Staphylococcus haemolyticus in 90% of the cases). Superimposed on 36% of these infants was GNB airway colonization with Klebsiella pneumoniae (25%), Enterobacter cloacae (25%), Escherichia coli (25%), Pseudomonas aeruginosa (10%), Serratia marcescen (10%), Acinetobacter baumannii and Haemophilus influenzae (5%). Comparison between 174 GPC- and 86 GNB-colonized infants showed that demographics, birth weight, gestational age, perinatal risk factors and mortality were similar. Fifteen percent of GNB-colonized infants developed BSI caused by GNB and 14% developed BSI caused by GPC. No significant temporal relationship between airway colonization and BSI was noted. GNB infants were ventilated longer and required oxygen at 36 weeks of postconceptional age and home oxygen supplementation twice as often as infants colonized only with GPC. GNB colonization was a predictor of severe BPD after controlling for ventilation. Ureaplasma colonization occurred in 28% of GNB-colonized and 33% of noncolonized infants and was not a predictor of BPD severity. CONCLUSION: GNB airway colonization creates a moderate risk for BSI. Antibiotic treatment does not regularly eradicate GNB. GNB airway colonization is associated with severe BPD, but further studies will be necessary before therapeutic efforts to eradicate GNB from the airways should be undertaken.

Bronchopulmonary Dysplasia↗

Rapid identification of micro-organisms from urinary tract infections by beta-glucuronidase, phenylalanine deaminase, cytochrome oxidase and indole tests on isolation media.

Two commercially available media recommended for the isolation and rapid identification of Escherichia coli from urinary tract infections were supplemented with L-phenylalanine and L-tryptophan. The non-selective medium proved suitable for the direct detection of lactose fermentation, beta-glucuronidase and phenylalanine deaminase activities, indole production and the oxidase test. It was highly efficient in making a presumptive identification at species level of the most common gram-negative urinary pathogens, E. coli, Proteus mirabilis and Pseudomonas aeruginosa, that account for c. 85% of all urinary isolates. Among the gram-positive isolates, most colonies were non-fluorescent and could be separated into staphylococci and enterococci on the basis of the catalase test. Fluorescent colonies were found to be Staphylococcus haemolyticus isolates, 61% of which were fluorescent. The selective medium proved suitable for the same biochemical tests, with the exception of indole, which was not visible against the red colour of the medium. Therefore, the differentiation of P. mirabilis from other Proteus-Providencia species was impossible on this medium.

Amino Acid Oxidoreductases↗

Intestinal microflora in early infancy: composition and development.

The neonatal intestinal microbiota is a complex ecosystem composed of numerous genera, species and strains of bacteria. This enormous cell mass performs a variety of unique activities that affect both the colonic and systemic physiology. Its primary activities include nutritive, metabolic, immunological and protective functions. Most studies of infants have been based on faecal samples using the classical plating techniques with culturing on specific media. The limitations of these methods must be taken into account when evaluating the varying results of the different studies. The establishment of the gut microbial population is not strictly a succession in the ecological sense; it is rather a complex process influenced by microbial and host interactions and by external and internal factors. The climax intestinal flora is attained in successive stages. The foetal intestine is sterile and bathed in swallowed amniotic fluid. Following delivery, multiple different antigens challenge the intestine of the newborn. The maternal intestinal flora is a source of bacteria for the neonatal gut. The bacterial flora is usually heterogeneous during the first few days of life, independently of feeding habits. After the first week of life, a stable bacterial flora is usually established. In full-term infants a diet of breast milk induces the development of a flora rich in Bifidobacterium spp. Other obligate anaerobes, such as Clostridium spp. and Bacteroides spp., are more rarely isolated and also enterobacteria and enterococci are relatively few. During the corresponding period, formula-fed babies are often colonized by other anaerobes in addition to bifidobacteria and by facultatively anaerobic bacteria; the development of a "bifidus flora" is unusual. In other studies the presence of a consistent number of bifidobacteria in infants delivered in large urban hospitals has not been demonstrated, whether the babies were bottle fed or exclusively breastfed. The predominant faecal bacteria were coliforms and bacteroides. According to these studies, environmental factors may be more important than breastfeeding in gut colonization after delivery. Environmental factors are indeed extremely important for the intestinal colonization of infants born by caesarean section. In these infants, the establishment of a stable flora characterized by a low incidence of Bacteroides spp. and by the isolation of few other bacteria is consistently delayed. In extremely low-birthweight infants, hospitalization in neonatal intensive care units, characterized by prolonged antibiotic therapy, parenteral nutrition, delayed oral feedings and intubation seems to affect the composition of the intestinal microbiota. The gut is colonized by a small number of bacterial species; Lactobacillus and Bifidobacteria spp. are seldom, if ever, identified. According to the few studies so far performed, the predominant species are Enterococcus faecalis, E. coli, Enterobacter cloacae, Klebsiella pneumoniae, Staphylococcus epidermidis and Staphylococcus haemolyticus. Hygienic conditions and antimicrobial procedures strongly influence the intestinal colonization pattern.

Anti-Bacterial Agents↗

Increase of faecal bifidobacteria due to dietary oligosaccharides induces a reduction of clinically relevant pathogen germs in the faeces of formula-fed preterm infants.

UNLABELLED: In a previous study on formula-fed preterm infants, we were able to demonstrate that dietary oligosaccharides (a mixture of 90% galacto-oligosaccharides and 10% fructo-oligosaccharides in a concentration of 1 g/dl) stimulate the growth of faecal bifidobacteria. In the present explorative analysis of this study, we focus on the effect of the dominance of bifidobacteria on the presence of clinically relevant pathogens (Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Proteus, Streptococcus group B, Clostridium difficile, Bacillus subtilis and Acinetobacter). CONCLUSION: The data demonstrate that stimulation of bifidobacteria by prebiotic oligosaccharides reduces the presence of clinically relevant pathogens in the faecal flora, indicating that prebiotic substances might have the capacity to protect against enteral infections.

Bacterial Infections↗