Performance of the PIRO score for predicting mortality in patients with ventilator-associated pneumonia.

The ventilator-associated pneumonia (VAP) PIRO score is a new scoring system based on the PIRO concept. The aim of this study was to validate the PIRO score against the Acute Physiology and Chronic Health Evaluation (APACHE) II and VAP APACHE II in an independent group of VAP patients. Areas under the receiver operating characteristic curves were compared to determine the tests' abilities to predict intensive care unit and 28-day mortality. Variables associated with intensive care unit mortality were evaluated. One hundred and forty-eight intensive care unit patients who met radiographic and clinical criteria for VAP were included. The area under the receiver operating characteristic curves for predicting intensive care unit mortality with the PIRO, APACHE II and VAP APACHE II scores were 0.605 (P=0.03), 0.631 (P=0.01) and 0.724 (P <0.0001), respectively. Areas under the receiver operating characteristic curve for predicting 28-day mortality were 0.614 (P=0.01) for PIRO, 0.633 (P=0.01) for APACHE II and 0.697 (P=0.002) for VAP APACHE II. No differences in area under the receiver operating characteristic curve between scores were found at either endpoint. Variables independently associated with intensive care unit mortality were bacteraemia (adjusted odds ratio 7.16, 95% confidence interval 1.19 to 42.98, P=0.03) and APACHE II (1.06, 1.01 to 1.11, P=0.006). VAP PIRO score was not a good predictor of intensive care unit and 28-day mortality. The low sensitivity and specificity of VAP PIRO score preclude its use clinically.

A pharmacodynamic simulation to assess tigecycline efficacy for hospital-acquired pneumonia compared with other common intravenous antibiotics.

A pharmacodynamic model was used to generate supportive data comparing tigecycline with other broad-spectrum agents against pathogens implicated in hospital-acquired pneumonia (HAP). A 5000 patient Monte Carlo simulation determined the probability of target attainment (PTA) of tigecycline (+/- ceftazidime) compared with imipenem, levofloxacin, and piperacillin/tazobactam (+/- vancomycin). PTA was calculated over MICs of current Gram-positive and Gram-negative bacteria collected from worldwide surveillance and weighted by the expected prevalence of these pathogens causing HAP. For monotherapy, the weighted PTA was imipenem (78.2%), piperacillin/tazobactam (73.3%), tigecycline (62.9%), and levofloxacin (62.5%). By pathogen PTA was greatest for tigecycline against Gram-positives, and ceftazidime or imipenem against Gram-negatives. Combination therapy increased PTA to 88.6%, 85.5%, 80.6%, and 69.8% for tigecycline, imipenem, piperacillin/tazobactam, and levofloxacin, respectively. Based on contemporary resistance data, tigecycline plus ceftazidime is predicted to achieve its pharmacodynamic targets similarly to combination therapy with imipenem plus vancomycin for the treatment of patients with HAP.

Pharmacodynamic comparison of linezolid, teicoplanin and vancomycin against clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci collected from hospitals in Brazil.

Pharmacodynamic exposures, measured as the ratio of steady-state total drug area under the curve to MIC (AUC/MIC), were modelled using a 5000-patient Monte-Carlo simulation against 119 non-duplicate clinical isolates of Staphylococcus aureus and 82 coagulase-negative staphylococci (CNS) collected from hospitals in Brazil between 2003 and 2005. Pharmacodynamic targets included an AUC/MIC >82.9 for linezolid and >345 for teicoplanin and vancomycin, as well as a free drug AUC/MIC >180 for vancomycin. The cumulative fractions of response (CFRs) against all S. aureus isolates were 96.0%, 30.1%, 71.6%, 48.0% and 65.1% for linezolid 600 mg every 12 h, teicoplanin 400 mg every 24 h and 800 mg every 24 h, and vancomycin 1000 mg every 12 h and every 8 h, respectively. Using a free drug target for vancomycin improved the CFR to 94.6% for the high-dose regimen, but did not substantially alter results for the lower dose. CFRs against all CNS isolates were 97.8%, 13.4%, 34.6%, 10.9% and 31.3%, respectively, for the same antibiotic regimens. The CFR was reduced for all compounds among the methicillin-resistant isolates, except for linezolid against methicillin-resistant CNS. Sensitivity analyses did not alter the final order of pharmacodynamic potency against these isolates. Although higher doses of vancomycin and teicoplanin increased the CFR, the likelihood of achieving bactericidal targets was still lower than with linezolid. The results for the high-dose vancomycin regimen were highly dependent on the pharmacodynamic target utilised. These data suggest that linezolid has a greater probability of attaining its requisite pharmacodynamic target than teicoplanin and vancomycin against these staphylococci.

Addressing resistance evolution in Pseudomonas aeruginosa using pharmacodynamic modelling: application to meropenem dosage and combination therapy.

Isolates of Pseudomonas aeruginosa (n = 208) were collected from an 810-bed hospital in Connecticut, USA. A model employing the pharmacokinetic properties of meropenem, susceptibility results and Monte Carlo simulation was used to analyse four different dosing regimens of meropenem at pharmacodynamic endpoints. Cumulative fraction of response (CFR) was assessed at bacteriostatic and bactericidal endpoints for the entire population of isolates, as well as for isolates from principal anatomical sites. CFR was also evaluated at endpoints shown to suppress emergence of resistance in 'susceptible'P. aeruginosa with either monotherapy or combination therapy. The bacteriostatic/bactericidal CFR of meropenem 1 g every 8 h (q8h), 2 g q8h, 1 g q8h infused over 3 h (3-h INF), and 2 g q8h 3-h INF were 76%/73%, 80%/76%, 77%/75% and 79%/78%, respectively. At the monotherapeutic suppressive endpoint, CFRs against susceptible isolates were 21%, 35%, 32% and 50%, respectively. When combination therapy with an aminoglycoside was simulated, the CFRs for the same regimens were 50%, 64%, 65% and 79%, respectively. Bactericidal CFRs for all regimens against wound isolates were significantly higher (p <0.03 for each regimen) than CFRs for the entire population. Meropenem 2 g q8h with a 3-h infusion in combination with an aminoglycoside provides the greatest likelihood of P. aeruginosa coverage, and may help to prevent development of resistance, although local MIC data are essential to inform therapeutic decisions.

Proximate composition and mineral content of two edible species of Cnidoscolus (tree spinach).

Proximate composition and mineral content of raw and cooked leaves of two edible tree spinach species (Cnidoscolus chayamansa and C. aconitifolius), known locally as 'chaya', were determined and compared with that of a traditional green vegetable, spinach (Spinicia oleraceae). Results of the study indicated that the edible leafy parts of the two chaya species contained significantly (p<0.05) greater amounts of crude protein, crude fiber, Ca, K, Fe, ascorbic acid and beta-carotene than the spinach leaf. However, no significant (p>0.05) differences were found in nutritional composition and mineral content between the chaya species, except minor differences in the relative composition of fatty acids, protein and amino acids. Cooking of chaya leaves slightly reduced nutritional composition of both chaya species. Cooking is essential prior to consumption to inactivate the toxic hydrocyanic glycosides present in chaya leaves. Based on the results of this study, the edible chaya leaves may be good dietary sources of minerals (Ca, K and Fe) and vitamins (ascorbic acid and beta-carotene).

Typhoid fever associated with severe hepatitis.

While typhoid is quite common in our environment, presentation in association with severe hepatitis and hepatic encephalopathy is uncommon. The case of a 14 year old male with typhoid who presented with jaundice and severe hepatitis with encephalopathy is presented. The first symptoms occurred one week before presentation. The clinical features and laboratory investigations confirmed typhoid fever. The associated severe hepatitis could have been related to a direct liver involvement by Salmonella typhi, drug toxicity or hepatitis B infection from previous indiscriminate parenteral drugs. The specific cause of the hepatitis could not be confirmed. The patient is presented to illustrate a rare association and possible complication of typhoid fever, inappropriate self and other medication in the place of proper hospital presentation and assessment and the diagnostic difficulties confronting many centres in the developing environment.

Severe large and small bowel fibrosis clinically mimicking gross splenomegaly.

The case of an 18-year-old female, with mild left hypochondrial pain and an abdominal mass mimicking gross splenomegaly, with severe small and large bowel fibrosis and adhesions and numerous mononuclear cellular infiltrate on histology, is presented. A clear picture of intestinal obstruction only unfolded terminally. She died within 48 hours of presentation. Our patient illustrates the fact that severe intestinal adhesions may present with very mild symptoms and signs and therefore a high index of suspicion is necessary, to reduce the attendant high mortality in intestinal obstruction in our environment.

Allelochemical regulation of reproduction and seed germination of two BrazilianBaccharis species by phytotoxic trichothecenes.

The potent phytotoxic trichothecene roridins and baccharinoids occur naturally in the Brazilian plants,Baccharis coridifolia andB. megapotamica. Biosynthesis of roridins inB. coridifolia appears to be linked to pollination, and the phytotoxins then accumulate in the seed. The roles of the phytotoxins in pollination, seed maturation, and germination of theBaccharis species were investigated. The high production of roridins occurred only in seeds resulting from intraspecific pollination, and the concentration of the toxins in the seeds generally increased with seed maturity. Removal of seed coats from trichothecene-producing BrazilianBaccharis species (B. coridifolia andB. megapotamica) and non-trichothecene-producing AmericanBaccharis species (B. halimifolia andB. glutinosa) resulted in improved seed germination ofB. halimifolia andB. glutinosa but complete inhibition of seed germination ofB. coridifolia andB. megapotamica. Addition of seed coat extracts of the BrazilianBaccharis species of dilute solutions (10(-6)µg/ml) of roridins or baccharinoids to the decoated seeds ofB. coridifolia andB. megapotamica resulted in germination, while seeds ofB. halimifolia andB. glutinosa were killed by the phytotoxins. Roridins interacted with gibberellic acid, a germination promoter, but not with abscisic acid, a germination inhibitor. The results from this study suggest that macrocyclic trichothecenes have a regulatory role(s) on reproduction and germination of BrazilianBaccharis species in their natural habitat.

Casual blood glucose levels and prevalence of undiscovered diabetes mellitus in Lagos Metropolis Nigerians.

A diabetic screening exercise involving 1627 subjects (1050 males and 577 females) was carried out in the Lagos Metropolis of Nigeria. Casual capillary blood glucose and/or urine glucose were tested for by means of dipsticks. The prevalence rates of undetected diabetes in the males and females were respectively 1.5% and 1.9%. Mean (+/- SD) casual blood glucose levels were higher in the females (82.8 (+/- 19.1) mg/100 ml) than in the males (75.9 (+/- 16.2) mg/100 ml). The prevalence of renal glycosuria was 1.3% in the males and 0.2% in the females. The prevalence of diabetes mellitus in the Lagos Metropolis appears high but similar to that in many other countries. The ambient blood glucose in the non-hospitalized subjects also seems to be not significantly different from values reported in other places.

Influence of methodology on glycosylated hemoglobin values in Nigerian subjects with sickle cell hemoglobinopathy.

The determination of glycosylated hemoglobin (GHb) has been found useful in the medium term assessment of diabetic control. Levels of GHb have been shown to be influenced by hematological abnormalities and methodology amongst other factors. Hemoglobinopathies are common in Nigerians and other people of African descent. No work, to our knowledge, has been done in Nigeria to study the effect of hemoglobinopathies on the levels of GHb in Nigerians or Africans. In this study, GHb levels in non-diabetic Nigerians (with hemoglobin genotypes AA, AS, and SS) were determined by short column chromatography and thiobarbituric acid colorimetry. Levels of GHb obtained by the microchromatographic method were significantly different from one another in the three subject groups. The group mean GHb level was highest in subjects with sickle cell anaemia and lowest in subjects with sickle cell trait. However, using the colorimetric method, the mean GHb level of the normal subjects with hemoglobin genotype AA was not significantly different from that of subjects with hemoglobin genotype AS or SS. Results of GHb determinations by microchromatography (for which several commercial kits are available) in subjects with sickle cell anemia or trait must be interpreted with caution. The colorimetric method, though more tedious, gives more reliable results and should be the method of choice in subjects with concurrent diabetes and sickle cell anemia or trait.