Efficacy of rifampin, in monotherapy and in combinations, in an experimental murine pneumonia model caused by panresistant Acinetobacter baumannii strains.

The objective of this work was to evaluate the efficacy of rifampin, and its combinations with imipenem or sulbactam, in an experimental pneumonia model caused by two panresistant Acinetobacter baumannii strains (HUVR99 and HUVR113). Minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) (µg/ml) of the strains were rifampin 128/>128 for both strains, imipenem 128/>256 and 256/>256 for HUVR99 and HUVR113, respectively, and sulbactam >256/>256 for both strains. In time-kill studies, at MICs, rifampin was bactericidal for both strains and sulbactam against the HUVR99 strain. Rifampin plus imipenem or sulbactam, at the MIC or mice C (max), were synergistic. In vivo, against HUVR99 and HUVR113, rifampin (73% and 40%) and its combinations improved the survival with respect to the control group (20% and 0%, p < 0.05), respectively. Rifampin (87% and 46%) and its combinations improved the sterilization of blood cultures with respect to the control groups (0%, p < 0.05). In regard to the bacterial clearance from lungs, rifampin (2.57 ± 2.47 and 5.35 ± 3.03 log(10) cfu/g) and its combinations with imipenem or sulbactam diminished the bacterial lung concentration with respect to the control group (10.89 ± 3.00 and 11.86 ± 0.49, p < 0.05) with both strains. In conclusion, rifampin alone or associated to imipenem or sulbactam were effective for the treatment of murine pneumonia caused by selected panresistant A. baumannii strains.

Efficacy of tigecycline vs. imipenem in the treatment of experimental Acinetobacter baumannii murine pneumonia.

The in vivo activity of tigecycline was evaluated in an experimental pneumonia model (C57BL/6 mice) by Acinetobacter baumannii. Two clinical strains were used: minimum inhibitory concentrations (MICs) of imipenem and tigecycline 1 and 2 microg/mL (imipenem-susceptible, IPM-S), and 8 and 2 microg/mL (imipenem-intermediate, IPM-I), respectively. For imipenem (30 mg/Kg), T/CMI (h) were 1.04 and 0.51 for IPM-S and IPM-I, respectively. For tigecycline (5 mg/Kg), the area under the concentration-time curve (AUC)/MIC(0-24 h) (serum and lung) were 9.24 and 4.37 (for the two strains), respectively. In the efficacy experiments with the IPM-S, imipenem (log CFU/g 3.59 +/- 0.78, p = 0.006) and tigecycline (2.82 +/- 1.2, p = 0.054) decreased the bacterial counts in lungs with respect to its controls; with the IPM-I, both imipenem (1.21 +/- 0.52, p = 0.002) and tigecycline (3.21 +/- 0.28, p = 0.035) decreased the bacterial counts with respect to the controls. In the survival experiments, with the IPM-S, the mortality was the same in the control (67%) and in the tigecycline (77%) groups, and imipenem reduced it (21%, p = 0.025); with the IPM-I, the mortality was the same in the control (87%) and in the tigecycline (85%) groups, and imipenem (0%) reduced it (p < 0.001). In summary, the present study shows that tigecycline is less efficacious than imipenem in the treatment of experimental A. baumannii pneumonia caused by IPM-S and IPM-I strains.

[Analysis of gastric emptying dynamics in relationship to qualitative composition of intake. Comparison between normal-weight and obese subjects]. / Análisis de la dinámica de vaciamiento gástrico en relación con la composición cualitativa de la ingesta. Comparación entre sujetos con normopeso y obesos.

AIMS: To analyze whether the gastric emptying profile could define obesity and to study the impact of macronutrients diet composition on gastric emptying in obese and non obese people. MATERIAL AND METHODS: 47 subjects were selected (12 non obese and 35 obese). The study was organized in 4 visits. In each visit the subject was given isocaloric breakfast differing in macronutrient composition, (either equilibrated, or lipid, protein or carbohydrate rich) quantitative gastric emptying assay was done realized, every 15 minutes for two hours using a radionuclide technique. The week prior to the visit, the subject followed a standard 1,800 cal/day diet. RESULT: A significant interaction between time and diet composition is shown regardless of the group (obese or non-obese) the subject belongs to. The different macronutrient composition differentially affected gastric emptying only in the obese group. Post hoc analysis of the results showed significant differences after 45 min post breakfast between protein and carbohydrate rich breakfast. CONCLUSIONS: Gastric emptying in obese but not in non obese subjects, was significantly modified depending on the intake qualitative composition. These differences are clear when protein rich (significantly slower emptying) is compared versus hydrocarbon enriched diet (significantly faster emptying). A significant difference in gastric emptying between obese and non-obese subjects cannot be established.

Análisis de la dinámica de vaciamiento gástrico en relación con la composición cualitativa de la ingesta. Comparación entre sujetos con normopeso y obesos / Analysis of gastric emptying dynamics in relationship to qualitative composition of intake. Comparison between normal weight and obese subjects

Objetivos. Analizar si el perfil de vaciamiento gástrico podría ser característico en obesidad y estudiar el impacto que la relación de macronutrientes en la dieta tiene sobre el vaciamiento gástrico y las diferencias entre obesos y normopesos. Material y método. Se seleccionan 47 sujetos (12 normopeso y 35 obesos), que realizan 4 visitas durante el estudio. En cada una se administraba un desayuno isocalórico con distinta composición de macronutrientes (equilibrados, lipídico, proteico o hidrocarbonato). Se realizaron estudios cuantitativos de vaciamiento gástrico cada 15 minutos durante dos horas usando la técnica de gammagrafía. La semana previa a cada visita todos los sujetos realizaron una dieta estándar de 1.800 cal/día. Resultados. Se observa una interacción significativa entre los factores tiempo y dieta. Sin embargo, el mismo análisis no demostró esta tendencia al estudiar la evolución del vaciamiento en relación con el grupo al que pertenecía el sujeto (normopeso u obeso). La composición cualitativa de la dieta sólo influyó sobre el vaciamiento gástrico en obesos. El estudio post hoc demostró diferencias significativas fundamentalmente a partir de los 45 minutos postingesta, y entre ingestas ricas en hidratos de carbono y proteínas. Conclusiones. La composición cualitativa de la ingesta ha influido de forma significativa sobre la velocidad de vaciamiento gástrico en sujetos obesos, pero no en normopesos. Esta influencia se hace más evidente en la dieta hidrocarbonada (vaciamiento significativamente más rápido) y proteica (vaciamiento significativamente más lento). No puede establecerse una diferencia significativa de la velocidad de vaciamiento gástrico entre sujetos obesos o normopeso

Aims. To analyze whether the gastric emptying profile could define obesity and to study the impact of macronutrients diet composition on gastric emptying in obese and non obese people. Material and methods. 47 subjects were selected (12 non obese and 35 obese). The study was organized in 4 visits. In each visit the subject was given isocaloric breakfast differing in macronutrient composition, (either equilibrated, or lipid, protein or carbohydrate rich) quantitative gastric emptying assay was done realized, every 15 minutes for two hours using a radionuclide technique. The week prior to the visit, the subject followed a standard 1,800 cal/day diet. Result. A significant interaction between time and diet composition is shown regardless of the group (obese or non obese) the subject belongs to. The different macronutrient composition differentialy affected gastric emptying only in the obese group. Post hoc analysis of the results showed significant differences after 45 min post breakfast between protein and carbohydrate rich breakfast. Conclusions. Gastric emptying in obese but not in non obese subjects, was significantly modified depending on the intake qualitative composition. These differences are clear when protein rich (significantly slower emtying) is compared versus hydrocarbon enriched diet (significantly faster emptying). A significant difference in gastric emptying between obese and non obese subjects cannot be stablished

Pharmacokinetic/pharmacodynamic assessment of the in-vivo efficacy of imipenem alone or in combination with amikacin for the treatment of experimental multiresistant Acinetobacter baumannii pneumonia.

A guinea-pig pneumonia model involving imipenem-susceptible and imipenem-resistant strains of Acinetobacter baumannii was developed to assess the in-vitro and in-vivo activities of imipenem, alone or in combination with amikacin, and the pharmacokinetic and pharmacodynamic parameters. Serum levels were measured by bioassay (imipenem) or immunoassay (amikacin), followed by calculation of pharmacokinetic and pharmacodynamic parameters (Cmax, AUC, t1/2, Cmax/MIC, AUC/MIC, and Deltat/MIC). In-vivo efficacy was evaluated by comparing bacterial counts in the lungs of treatment groups with end-of-therapy controls by anova and post-hoc tests. Decreases in the Cmax (13.4%), AUC (13%), t1/2 (25%) and Deltat/MIC (11.8-32.2%) of imipenem were observed when it was administered with amikacin, compared with administration of imipenem alone. Similarly, decreases in the Cmax (34.5%), AUC (11.6%), Cmax/MIC (34.5%) and AUC/MIC (11.7%) of amikacin were observed when it was administered with imipenem. Bacterial counts in lungs were reduced by imipenem (p 0.004) with the imipenem-susceptible strain, and by amikacin (p 0.001) with the imipenem-resistant strain. The combination of imipenem plus amikacin was inferior to imipenem alone with the imipenem-susceptible strain (p 0.01), despite their in-vitro synergy, and was inferior to amikacin alone with the imipenem-resistant strain (p < 0.0001). In summary, combined use of imipenem with amikacin was less efficacious than monotherapy, probably because of a drug-drug interaction that resulted in decreased pharmacokinetic and pharmacodynamic parameters for both antimicrobial agents.

Reliability of the E-test method for detection of colistin resistance in clinical isolates of Acinetobacter baumannii.

We compared the E-test to the broth microdilution method for testing the susceptibility of 115 clinical isolates of Acinetobacter baumannii to colistin. Twenty-two (19.1%) strains were resistant to colistin and 93 (80.8%) strains were susceptible according to the reference broth microdilution method. A categorical agreement of 98.2% was found, with only two (1.7%) very major errors. Agreement within 1 twofold dilution between the E-test and the broth microdilution was 16.5%. Complete agreement was found for the strains for which MICs fell within the range of 0.25 to 1 microg of colistin/ml. However, there was poor concordance, particularly in extreme dilutions with higher MICs by the E-test method.

Morphological changes induced by imipenem and meropenem at sub-inhibitory concentrations in Acinetobacter baumannii.

Abstract Sub-inhibitory concentrations of imipenem and meropenem were evaluated for their ability to induce morphological changes with six strains of Acinetobacter baumannii isolated from patients with nosocomial pneumonia. Three strains were susceptible and three were resistant to carbapenems. The strains were grown in the presence of 0 (controls), 0.25x, 0.5x and 1x the MIC of both carbapenems for 4 h, and then examined after Gram's stain. Cells > or = 3 microm in size (spheroplasts) were considered to be altered. Both carbapenems induced significant numbers of spheroplasts compared to controls. Imipenem had more effect against susceptible strains, while meropenem had a greater effect against resistant strains.

Colistin efficacy in an experimental model of Acinetobacter baumannii endocarditis.

The in-vivo activity of colistin was evaluated in an experimental rabbit model of Acinetobacter baumannii endocarditis with a strain susceptible to colistin and intermediate to imipenem. Compared to a control group, colistin was effective (p < 0.05) in bacterial clearance from blood and in the sterilisation of blood cultures, but was not effective in clearing A. baumannii from vegetations. Thus, although colistin may be effective in treating bacteraemia caused by susceptible strains of A. baumannii, it may not be a suitable treatment for endocarditis, perhaps because of poor penetration into vegetations and a low C(max)/MIC ratio in tissue.

Cálculo de las volemias mediante dilución isotópica. Revisión teórica y práctica / Calculation of the blood volume with isotopic dilution. Theoretical and practical review

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Transfusion of blood components and postoperative infection in patients undergoing cardiac surgery.

OBJECTIVE: To investigate the influence of blood derivatives on the acquisition of severe postoperative infection (SPI) in patients undergoing heart surgery. SETTING: The postoperative ICUs of a tertiary-level university hospital. DESIGN: A cohort study. METHODS: During a 4-year period, 738 patients, classified as patients with SPIs and patients without SPIs (non-SPI patients), were included in the study. We studied the influence of 36 variables on the development of SPI in general and individually for pneumonia, mediastinitis, and/or septicemia. The influence of the blood derivatives on infections was assessed for RBC concentrates, RBC and plasma, and RBC and platelets. RESULTS: Seventy patients (9.4%) were classified as having SPIs, and 668 (90.6%) were classified as not having SPIs. After multivariate analysis, the variables associated with SPI (incidence, 9.4%) were reintubation, sternal dehiscence, mechanical ventilation (MV) for > or = 48 h, reintervention, neurologic dysfunction, transfusion of > or = 4 U RBCs, and systemic arterial hypotension. The variables associated with nosocomial pneumonia (incidence, 5.9%) were reintubation, MV for > or = 48 h, neurologic dysfunction, transfusion of > or = 4 U blood components, and arterial hypotension. The variables associated with mediastinitis (incidence, 2.3%) were reintervention and sternal dehiscence, and those associated with sepsis (incidence, 1.6%) were reintubation, time of bypass > or = 110 min, and MV for > or = 48 h. The mortality rate (patients with SPI, 52.8%; non-SPI patients, 8.2%; p < 0.001) and mean (+/- SD) length of stay in the ICU (patients with SPI, 15.8 +/- 12.9 days; non-SPI patients, 4.5 +/- 4.4 days; p < 0.001) were greater for the infected patients. The transfused patients also had a greater mortality rate (13.3% vs 8.9%, respectively; p < 0.001) and a longer mean stay in the ICU (6.1 +/- 7.2 days vs 3.7 +/- 2.8 days, respectively; p < 0.01) than those not transfused. CONCLUSION: The administration of blood derivatives, mainly RBCs, was associated in a dose-dependent manner with the development of SPIs, primarily nosocomial pneumonia.

Sulbactam efficacy in experimental models caused by susceptible and intermediate Acinetobacter baumannii strains.

Sulbactam and imipenem were compared in an experimental pneumonia model in immunocompetent mice, using a susceptible strain of Acinetobacter baumannii, and in an experimental endocarditis model in rabbits, using an intermediately susceptible strain. In the former, sulbactam was as efficacious as imipenem in terms of survival, sterility of lungs and in the bacterial clearance from lungs and blood, provided that the t > MIC for sulbactam (1.84 h) was similar to that for imipenem (2.01 h). In the endocarditis model, imipenem (t > MIC, 2.12 h) was more efficacious than sulbactam (t > MIC, 1.17 h) in bacterial clearance from vegetations. These results show the efficacy of sulbactam in infections caused by susceptible strains of A. baumannii, with an MIC up to 4 mg/L, provided that doses reach a t > MIC similar to that of imipenem. The activity of sulbactam was time dependent.

Nosocomial pneumonia in patients undergoing heart surgery.

OBJECTIVE: To determine the risk factors related to the presence of postsurgical nosocomial pneumonia (NP) in patients who had undergone cardiac surgery. DESIGN: A case-control study. SETTING: Postcardiac surgical intensive care unit at a university center. PATIENTS: A total of 45 patients with NP and 90 control patients collected during a 4-yr period. INTERVENTIONS: Pre-, intra-, and postoperative factors were collected and compared between two groups of patients (cases vs. controls) to determine their influence on the development of NP. The diagnosis of NP was always microbiologically confirmed as pulmonary specimen brush culture of > or =10(3) colony-forming units/mL or positive blood culture/pleural fluid culture by the growth of identical microorganisms isolated at the lung. For each patient diagnosed with NP, we selected control cases at a ratio of 1:2. MEASUREMENTS AND MAIN RESULTS: The incidence of NP was 6.5%. Multivariate analysis found a probable association of the following variables with a greater risk for the development of NP: reintubation (adjusted odds ratio [AOR], 62.5; 95% confidence interval [CI], 8.1-480; p = .01); nasogastric tube (AOR, 19.7; 95% CI, 3.5-109; p = .01), transfusion of > or =4 units of blood derivatives (AOR, 12.8; 95% CI, 2-82; p = .01) and empirical treatment with broad-spectrum antibiotics (AOR, 6.6; 95% CI, 1.2-36.8; p = .02). Culture results showed 13.3% of the NP to be of polymicrobial origin, whereas 77.3% of the microorganisms isolated were Gram-negative bacteria. The mortality (51 vs. 6.7%, p < .01) and the length of stay in the intensive care unit (25+/-14.8 days vs. 5+/-5 days, p < .01) were both greater in patients with NP. CONCLUSIONS: We conclude that the surgical risk factors, except the transfusion of blood derivatives, have little effect on the development of NP. Reintubation, nasogastric tubing, previous therapy with broad-spectrum antibiotics, and blood transfusion are factors most likely associated with NP acquisition.

Imipenem, doxycycline and amikacin in monotherapy and in combination in Acinetobacter baumannii experimental pneumonia.

Acinetobacter baumannii is a common cause of nosocomial pneumonia and other nosocomial infections. Multiresistant A. baumannii has also a high prevalence, which can make effective treatment difficult. We designed a new model of A. baumannii experimental pneumonia using C57BL/6 immunocompetent mice. This model was used to compare the efficacy of imipenem, doxycycline and amikacin in monotherapy, and the combination of imipenem plus amikacin and doxycycline plus amikacin. Doxycycline plus amikacin were synergic in vitro after 24 h incubation, whereas imipenem plus amikacin showed no in vitro synergy. The number of sterile lungs and the lung clearance of A. baumannii were greater in the group treated with imipenem than in those treated with amikacin or doxycycline in monotherapy (P < 0.05). The combination of imipenem plus amikacin and doxycycline plus amikacin was no more effective than imipenem alone in the clearance of organisms from lungs (2.42 +/- 1.46 cfu/g versus 2.7 +/- 1.5 cfu/g versus 1.23 +/- 1.02 cfu/g). These results suggest that the addition of amikacin does not improve the results obtained by imipenem monotherapy. Doxycycline plus amikacin is an alternative to imipenem in the therapy of A. baumannii pneumonia.

[Septic paniculitis and 67Ga scintigraphy]. / Paniculitis séptica y gammagrafía con 67 Ga.

A 50 year-old patient presenting septicemia, septic panniculitis from Staphylococcus aureus and skin lesions on the buttocks, thighs and left arm was referred to the Nuclear Medicine Service, with a suspected underlying osseus problem. A whole body scan with 67Ga revealed generalized disease of the soft tissues with no bone involvement. Gallium was used for the monitor of the evolution of the lesions, since this is a good indicator of the treatment effectiveness. In this case, the use of nuclear techniques was fundamental for diagnosing the spread and evolution of the lesions until they were cured (cured being considered as when there is no gallium uptake by the lesions, months prior to this stage).

[Resistant Streptococcus pneumoniae]. / Streptococcus pneumoniae resistente.

Streptococcus pneumoniae is a common pathogen in children that in recent years has shown a progressive rise in resistance to the usual antibiotics and also to the new third generation cephalosporins. We report a review of Streptococcus pneumoniae strains isolated at our hospital from pediatrics patients in whom we observed an increased incidence of resistance to cefotaxime significantly related with the rise in resistance to penicillin. The resistance of penicillin-resistant strains to various antibiotics was analyzed and the following results were obtained: cefotaxime, 0% susceptible, 83% intermediate and 17% resistant; erythromycin, 16,7% susceptible, 8,3& intermediate and 75% resistant; vancomycin, 100% susceptible; chloramfenicol, 16,7% susceptible and 83,3% resistant; and cotrimoxazole, 100% resistant.

Thyroid nodules. Role of fine needle aspiration and intraoperative frozen section examination.

OBJECTIVE: To determine the accuracy of fine needle aspiration (FNA) and intraoperative frozen section examination (IFSE) on thyroid nodules. STUDY DESIGN: The study group consisted of 470 patients who underwent thyroidectomy. FNA was performed on 289 patients and IFSE on 326. The FNA and IFSE results were compared with the final histologic diagnosis obtained after examination of permanent sections. RESULTS: The overall FNA sensitivity was 65%, specificity 88% and positive predictive value 61%. The IFSE sensitivity was 50%, and the specificity and positive predictive value were 100%. When both procedures were used together, FNA identified 16 of 45 (36%) carcinomas as malignant and an additional 13 (29%) as follicular proliferative lesions; IFSE correctly identified only 23 of 45 (51%) carcinomas. CONCLUSION: FNA provides enough information for determining the extent of thyroid surgery when a diagnosis of cancer is made. However, IFSE should be considered a supplementary procedure when FNA is not positive for cancer.

Appearance of resistance to beta-lactam antibiotics during therapy for Streptococcus pneumoniae meningitis.

A young boy had meningitis caused by Streptococcus pneumoniae that was relatively resistant to penicillin and susceptible to cefotaxime. After 10 days of therapy with penicillin and cefotaxime, fever recurred and a second lumbar puncture revealed a pneumococcus that was resistant to all beta-lactam antibiotics. We now add vancomycin to empiric third-generation cephalosporin therapy for meningitis in children when gram-positive cocci are seen on the cerebrospinal fluid smear.