Range Of Serious Infections Research Articles

Laboratory diagnosis of bloodstream infections caused by extended-spectrum ß-lactamase-producing E. coli and Klebsiella species

Extended-spectrum ß-lactamase (ESBL)-producing organisms are resistant to the third-generation cephalosporins commonly used as empirical therapy for a wide range of serious infections. It is therefore important for laboratories to offer reliable ESBL detection methods. This study compares two combination disc methods (Oxoid and Mast Diagnostics) containing cepodoxime with and without clavulanate with Vitek 2 for routine detection of ESBLs in Escherichia coli and Klebsiella spp. isolated from blood cultures. From December 2003 to April 2005, a total of 58 potential ESBL-producing isolates (resistant to cefotaxime and/or ceftazidime) by BSAC disc susceptibility were tested by the combination discs and Vitek 2. The Advanced Expert System, a feature of Vitek 2 reports possible mechanisms of resistance, based on interpretive reading of MICs. This study detected 7.4% more ESBL-producing isolates by Vitek 2 than by Oxoid disc testing (95% CI: 0.15–14.7%; P<0.2) and 31.6% more ESBL-producing isolates were detected by Vitek 2 than by Mast disc testing, (95% CI: 16.2–46.96%; P<0.001). Batch-to-batch variation was evident in disc performance for both disc types. Thus, use of appropriate controls is recommended when testing by the combination disc methods. Although no phenotypic test is 100% sensitive and specific, the Vitek 2 was a reliable system for ESBL detection; however, it is expensive and interpretation of results can be confusing to inexperienced users. Further studies to compare Vitek 2 with cefotaxime and ceftazidime combination discs may reveal disc methodology for ESBL detection to be a more reliable alternative than using cefpodoxime combination discs alone.

Microbiological assay for the determination of meropenem in pharmaceutical dosage form

Meropenem is a highly active carbapenem antibiotic used in the treatment of a wide range of serious infections. The present work reports a microbiological assay, applying the cylinder-plate method, for the determination of meropenem in powder for injection. The validation method yielded good results and included linearity, precision, accuracy and specificity. The assay is based on the inhibitory effect of meropenem upon the strain of Micrococcus luteus ATCC 9341 used as the test microorganism. The results of assay were treated statistically by analysis of variance (ANOVA) and were found to be linear ( r = 0.9999) in the range of 1.5–6.0 μg ml −1, precise (intra-assay: R.S.D. = 0.29; inter-assay: R.S.D. = 0.94) and accurate. A preliminary stability study of meropenem was performed to show that the microbiological assay is specific for the determination of meropenem in the presence of its degradation products. The degraded samples were also analysed by the HPLC method. The proposed method allows the quantitation of meropenem in pharmaceutical dosage form and can be used for the drug analysis in routine quality control.

Specific PCR detection of Peptostreptococcus magnus.

Peptostreptococcus magnus is the most pathogenic and one of the most common Gram-positive anaerobic cocci found in human clinical specimens. The organism has been isolated in pure culture from a range of serious infections, including meningitis and endocarditis. However, isolation of Peptostreptococcus magnus from the oral cavity has rarely been attempted. Identification of Peptostreptococcus magnus in clinical specimens is reliant upon microbiological culture and biochemical methods, which often give ambiguous results. The aim of this study was to develop a PCR assay for the specific detection of Peptostreptococcus magnus in oral clinical specimens. PCR primers specific for Peptostreptococcus magnus DNA were derived by comparison of 16S rRNA gene sequences and selection of primers that demonstrated specificity at their 3' ends for Peptostreptococcus magnus. PCR positivity for Peptostreptococcus magnus DNA was indicated by the amplification of a 553 bp product. The PCR assay was then used to attempt detection of Peptostreptococcus magnus DNA in subgingival plaque samples from adult periodontitis patients and pus aspirates from subjects with acute dento-alveolar abscesses. The PCR assay was demonstrated to be highly specific for Peptostreptococcus magnus DNA, since no PCR products were obtained when genomic DNA from a wide range of other oral bacteria, including closely related Peptostreptococcus species, was used in the PCR assay. Confirmation of specific amplification of Peptostreptococcus magnus DNA was obtained by digestion of PCR products with the restriction endonuclease RsaI, which gives a unique restriction profile for Peptostreptococcus magnus. Of the 33 subgingival plaque samples analysed, 2 (6 %) were positive for Peptostreptococcus magnus DNA. None of the 60 pus aspirates analysed was positive for Peptostreptococcus magnus DNA. It is concluded that Peptostreptococcus magnus is not a major pathogen in adult periodontitis or dento-alveolar abscesses. The PCR assay provides a more rapid, specific and sensitive alternative to conventional methods for identification of Peptostreptococcus magnus in clinical specimens.

Meropenem: clinical response in relation to in vitro susceptibility

To collate the clinical response and pathogen eradication rates for meropenem monotherapy with in vitro susceptibility of the causative pathogens. Data were compiled from 17 randomized clinical studies that compared meropenem monotherapy with standard treatment options, often combinations. A total of 4906 pathogens from lower respiratory tract, intra-abdominal, obstetric/gynecological, skin/soft tissue, meningitis, or pediatric infections were assessed. Of these, 3713 pathogens (1963 meropenem, 1750 comparators) were evaluable. The overall rates of satisfactory clinical response (cure or improvement) and pathogen eradication (eradication or presumed eradication) at the end of therapy were similar with meropenem (93% for both responses) and the comparators (92%), as were the rates in each infection type. For each pathogen, the clinical response and eradication rates with meropenem were similar across the minimum inhibitory concentration (MIC) range of < or = 0.25 to 4 mg/L. Overall, a satisfactory clinical response occurred in 93% (1580 of 1708) of infections caused by nonfastidious pathogens with MICs < or = 4 mg/L and in 84% (16 of 19) of those with an MIC of 8 mg/L. Pathogen eradication rates were similar (93 and 79%, respectively). A similar profile was observed for fastidious pathogens. The high rates of satisfactory clinical response and pathogen eradication produced by meropenem in each type of infection were generally independent of the causative pathogen, whether Gram-positive or -negative aerobe or anaerobe or when occurring as mono- or polymicrobial infections. The attractive in vitro profile of meropenem translates into good clinical efficacy. The National Committee for Clinical Laboratory Standards has now defined meropenem MIC breakpoints for nonfastidious aerobes or anaerobes as < or = 4 (susceptible), 8 (intermediate) and > or = 16 mg/L (resistant), respectively. The susceptibility breakpoint for Streptococcus spp. (excluding Streptococcus pneumoniae) is < or = 0.5 mg/L and, since meropenem is indicated for the treatment of meningitis, the susceptibility breakpoint for S. pneumoniae and Haemophilus influenzae is < or = 0.25 and < or = 0.5 mg/L, respectively. Meropenem monotherapy is therefore a valid option for the initial empirical treatment of a range of serious infections caused by single or multiple bacterial pathogens.

Meropenem: a review of its use in patients in intensive care.

Meropenem is a carbapenem antibacterial agent that has antimicrobial activity against gram-negative, gram-positive and anaerobic micro-organisms. In vitro studies involving isolates from patients in intensive care units (ICUs) indicate that meropenem is more active against most gram-negative pathogens than other comparators (including imipenem), although, compared with imipenem, meropenem is less active against most gram-positive organisms. Resistance to meropenem is uncommon in most bacteria. Treatment with meropenem as initial empirical monotherapy was effective in a range of serious infections in adult and paediatric ICU patients. Meropenem monotherapy was as effective as imipenem/cilastatin in 4 comparative trials in terms of satisfactory clinical and bacteriological responses. Meropenem monotherapy was significantly more effective than ceftazidime-based combination treatments in 2 trials in patients with nosocomial lower respiratory tract infections (LRTIs) in terms of both clinical and bacteriological responses. Meropenem was also more active than ceftazidime-based treatments against both gram-positive and gram-negative organisms. However, 2 studies in patients with a range of serious infections found no significant differences between meropenem and cephalosporin-based treatments in terms of clinical or bacteriological response. Meropenem was also as effective as cephalosporin-based treatments in comparative trials in children with serious infections. Meropenem is well tolerated as either a bolus or an infusion, and clinical trials have shown similar incidences of adverse events to those observed with cephalosporin-based treatments. It is well tolerated by the CNS, with seizures reported infrequently, and can therefore be used at high doses and in patients with meningitis. The incidence of drug-related nausea and vomiting is low and, in contrast to imipenem/cilastatin, does not increase with dose or speed of administration. Meropenem is a well tolerated broad spectrum antibacterial agent that, when used as initial empirical monotherapy, is as effective as imipenem/cilastatin in the treatment of a range of serious infections (including nosocomial) in adults and children in ICUs. Compared with cephalosporin-based combination treatments, meropenem monotherapy may be more effective in the treatment of nosocomial LRTIs and can be used as monotherapy. Meropenem has an important role in the empirical treatment of serious infections in adults and children in ICUs.

Meropenem. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy.

The parenteral carbapenem meropenem is relatively stable to inactivation by human renal dehydropeptidase (DHP-1) and does not require concomitant administration of a DHP-1 inhibitor such as cilastatin. It has a broad spectrum of antibacterial activity in vitro, the majority of Gram-negative, Gram-positive and anaerobic pathogens being highly susceptible to the drug. Meropenem has shown clinical and bacteriological efficacy in the treatment of a wide range of serious infections in adults and children which is at least comparable with that of currently available treatment options. Its clinical and bacteriological efficacy is similar to that of imipenem/cilastatin, clindamycin plus tobramycin and cefotaxime plus metronidazole in the treatment of intraabdominal infections; cefotaxime or ceftriaxone in the treatment of meningitis; imipenem/cilastatin, and ceftazidime with or without an aminoglycoside, in lower respiratory tract infections; and imipenem/cilastatin or ceftazidime in the treatment of urinary tract infections. Satisfactory clinical and bacteriological response rates have also been achieved in patients with skin and skin structure infections, obstetric and gynaecological infections or septicaemia, and in immunocompromised patients with febrile episodes. Preliminary findings also indicate efficacy in the treatment of respiratory tract infections in patients with cystic fibrosis. The tolerability profile of meropenem is generally similar to that of comparator agents, although it is associated with a lower incidence of adverse gastrointestinal effects (nausea and vomiting) than imipenem/cilastatin. Importantly, the incidence of seizures in patients with meningitis is not increased following administration of meropenem. Thus, meropenem is an effective broad spectrum antibacterial drug for the treatment of a wide range of infections including polymicrobial infections in both adults and children, with comparable efficacy to imipenem/cilastatin and various other treatment regimens. Meropenem is likely to be of greatest value as empiric monotherapy in the treatment of serious infections for those caused by multiply-resistant pathogens. Further clinical experience is necessary, however, to ultimately define its place in therapy.

Corynebacterium Jeikeium (group JK diphtheroids) endocarditis: A report of five cases

Corynebacterium jeikeium is the name recently given to a group of coryneform rods, formerly known as the JK group, and associated with a wide range of serious infections. We describe five patients with C. jeikeium endocarditis observed in two Belgian hospitals over a period of 5 years. In three cases, the infection occurred on prosthetic heart valves between 1.5 and 5 months after surgery. The two other patients, with known mitral insufficiency, presented with endocarditis on native valves. In four patients, bacteriologic and clinical cure followed treatment with vancomycin. The fifth patient died despite eradication of the coryneforms by combination antibiotic therapy. We know of no previous reports of C. jeikeium endocarditis on native heart valves.

Vancomycin in Pediatrics

Vancomycin, a complex glycopeptide antibiotic, has achieved somewhat limited use since its introduction in 1956. It has excellent antibacterial activity against a variety of Gram-positive organisms, including those resistant to semisynthetic penicillins such as methicillin. Because of its higher potential for adverse side effects, such as thrombophlebitis and ototoxicity, it should be reserved for illnesses associated with methicillin-resistant staphylococci or in patients who have serious allergies to the penicillins. It has shown excellent effectiveness in a wide range of serious infections due to Gram-positive bacteria. Vancomycin should be administered intravenously, except in the case of staphylococcal or pseudomembranous colitis associated with C difficile in which oral administration is the appropriate route. In infections with enterococci, combination with an aminoglycoside is indicated as synergism occurs. It is excreted by the kidney; extra care must be taken in treating patients with renal failure. Dosing in anephric patients undergoing dialysis is greatly simplified by its prolonged half-life and is usually necessary only every seven to 14 days. Monitoring the serum concentration is desirable in all patients receiving vancomycin to ensure an efficacious, but nontoxic level.

Vancomycin in Pediatrics

Vancomycin, a complex glycopeptide antibiotic, has achieved somewhat limited use since its introduction in 1956. It has excellent antibacterial activity against a variety of Gram-positive organisms, including those resistant to semisynthetic penicillins such as methicillin. Because of its higher potential for adverse side effects, such as thrombophlebitis and ototoxicity, it should be reserved for illnesses associated with methicillin-resistant staphylococci or in patients who have serious allergies to the penicillins. It has shown excellent effectiveness in a wide range of serious infections due to Gram-positive bacteria. Vancomycin should be administered intravenously, except in the case of staphylococcal or pseudomembranous colitis associated with C difficile in which oral administration is the appropriate route. In infections with enterococci, combination with an aminoglycoside is indicated as synergism occurs. It is excreted by the kidney; extra care must be taken in treating patients with renal failure. Dosing in anephric patients undergoing dialysis is greatly simplified by its prolonged half-life and is usually necessary only every seven to 14 days. Monitoring the serum concentration is desirable in all patients receiving vancomycin to ensure an efficacious, but nontoxic level.