Prognostic performance of neutrophil CD64 expression in patients with complicated intra-abdominal infections - a prospective study.

No study yet analyzed the prognostic abilities of neutrophil CD64 expression (nCD64) in complicated intra-abdominal infections (cIAIs), therefore our aim was to evaluate the possible association between this biomarker and outcome in such patients. This single-center prospective study was conducted in the Department of Surgical Diseases at a University Hospital 'Prof. Dr. Stoyan Kirkovich' Stara Zagora for the period November 2018 - August 2021. We used flow cytometry to measure the percentage of nCD64 preoperatively and on the 3rd postoperative day (POD) in 62 patients with cIAIs and 31 healthy controls. Of the 62 enrolled patients, nine (14.5%) died during hospitalization. The perioperative expression of nCD64 was significantly higher in non-survivors compared to survivors (p = 0.02 before surgery and p = 0.024 after surgery). ROC Curve analysis revealed the good prognostic value of pre- and postoperative nCD64 levels as mortality predictors (AUROC = 0.744 and 0.765, respectively). Preoperatively, the identified sensitivity and specificity for nCD64 cut-off = 94.8% were 66.7% and 84.6%, respectively and on the 3rd POD for nCD64 cut-off = 84.85% we observed a sensitivity of 71.4% and a specificity of 78.8%. Neutrophil CD64 shows good prognostic value in patients with cIAIs both preoperatively and on the 3rd POD.

The uroS and yifB Genes Conserved among Tetrapyrrole Synthesizing-Deficient Bacteroidales Are Involved in Bacteroides fragilis Heme Assimilation and Survival in Experimental Intra-abdominal Infection and Intestinal Colonization.

The human intestinal anaerobic commensal and opportunistic pathogen Bacteroides fragilis does not synthesize the tetrapyrrole protoporphyrin IX in order to form heme that is required for growth stimulation and survival in vivo Consequently, B. fragilis acquires essential heme from host tissues during extraintestinal infection. The absence of several genes necessary for de novo heme biosynthesis is a common characteristic of many anaerobic bacteria; however, the uroS gene, encoding a uroporphyrinogen III synthase for an early step of heme biosynthesis, is conserved among the heme-requiring Bacteroidales that inhabit the mammalian gastrointestinal tract. In this study, we show that the ability of B. fragilis to utilize heme or protoporphyrin IX for growth was greatly reduced in a ΔuroS mutant. This growth defect appears to be linked to the suppression of reverse chelatase and ferrochelatase activities in the absence of uroS In addition, this ΔuroS suppressive effect was enhanced by the deletion of the yifB gene, which encodes an Mg2+-chelatase protein belonging to the ATPases associated with various cellular activities (AAA+) superfamily of proteins. Furthermore, the ΔuroS mutant and the ΔuroS ΔyifB double mutant had a severe survival defect compared to the parent strain in competitive infection assays using animal models of intra-abdominal infection and intestinal colonization. This shows that the presence of the uroS and yifB genes in B. fragilis seems to be linked to pathophysiological and nutritional competitive fitness for survival in host tissues. Genetic complementation studies and enzyme kinetics assays indicate that B. fragilis UroS is functionally different from canonical bacterial UroS proteins. Taken together, these findings show that heme assimilation and metabolism in the anaerobe B. fragilis have diverged from those of aerobic and facultative anaerobic pathogenic bacteria.

Lactulose Breath Testing Can Be a Positive Predictor Before Weight Gain in Participants with Obesity Submitted to Roux-en-Y Gastric Bypass.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is defined as the colonization of fermentative bacteria in the duodenum and jejunum. The alteration of digestive anatomy promoted by bariatric surgery may be a pre-disposing factor for SIBO. In this context, the prevalence of SIBO in participants undergoing bariatric surgery using Roux-en-Y gastric bypass (BGYR) was evaluated. METHODS: Participants, both sexes, older than 18 years, were those who (a) had bariatric surgery by the BGYR technique at least 1 year before the data collection and (b) did not use antibiotics recently. The SIBO diagnosis was established through the hydrogen breath test (H2BT), with intake of lactulose and serial collection of breath samples over 2 h. A test with ≥ 12-point elevation over the basal sample at 60 min after substrate intake was deemed positive. RESULTS: A total of 18 participants (14 females (77.8%)) were enrolled with a mean age of 50.5 years (range, 23 to 79 years). The interval between surgery and data collection ranged from 5 to 20 years (mean, 11.2 years). The mean preoperative body mass index (BMI) was 44.6 kg/m2 (range, 36.7-56.2 kg/m2). The H2RT with lactulose was positive for SIBO in seven (six female) participants. The participants with negative test measured trough H2BT with lactulose had a lower mean BMI of 28.69 kg/m2, in comparison with the positive group, which presented a mean BMI of 33.04 kg/m2 (p value = 0.041). CONCLUSION: Our data point to a high prevalence of SIBO (38.8%) in patients undergoing BGYR with a value in accordance with the literature. Moreover, the differences in BMI between negative and positive groups by H2BT with lactulose evidenced a weight gain relapse in participants with SIBO.

Ceftolozane-Tazobactam Population Pharmacokinetics and Dose Selection for Further Clinical Evaluation in Pediatric Patients with Complicated Urinary Tract or Complicated Intra-abdominal Infections.

Ceftolozane-tazobactam, a combination of the novel antipseudomonal cephalosporin ceftolozane and the well-established extended-spectrum ß-lactamase inhibitor tazobactam, is approved for treating complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI) in adults. To determine doses likely to be safe and efficacious in phase 2 pediatric trials for the same indications, single-dose ceftolozane-tazobactam plasma pharmacokinetic data from a recently completed phase 1 trial in pediatric patients (birth to <18 years old) with proven/suspected Gram-negative bacterial infections, along with pharmacokinetic data from 12 adult studies, were integrated into a population pharmacokinetic (popPK) analysis. Two-compartment linear models with first-order elimination described the concentration-time profiles of ceftolozane and tazobactam in pediatric patients well. Renal function and body weight were identified to be significant predictors of ceftolozane-tazobactam pharmacokinetics. Renal function, as measured by the estimated glomerular filtration rate (eGFR), significantly affected the clearance of both ceftolozane and tazobactam. Body weight significantly affected clearance and the distribution volume, also of both ceftolozane and tazobactam. Patients with infections had a 32.3% lower tazobactam clearance than healthy volunteers. Using the final popPK models, simulations of various dosing regimens were conducted to assess each regimen's plasma exposure and the probability of pharmacokinetic/pharmacodynamic target attainment. Based on these simulations, the following doses are recommended for further clinical evaluation in phase 2 pediatric trials for cUTI and cIAI (in patients with an eGFR of ≥50 ml/min/1.73 m2 only): for children ≥12 years old, 1.5 g ceftolozane-tazobactam (1 g ceftolozane with 0.5 g tazobactam), and for neonates/very young infants, infants, and children <12 years old, 20/10 mg/kg of body weight ceftolozane-tazobactam, both via a 1-h intravenous infusion every 8 h.

Intra-abdominal infection combined with intra-abdominal hypertension aggravates the intestinal mucosal barrier dysfunction.

Some patients with intra-abdominal infection (IAI) may develop intra-abdominal hypertension (IAH) during treatment. The present study investigated the impact of IAI combined with IAH on the intestinal mucosal barrier in a rabbit model. Forty-eight New Zealand white rabbits were randomly divided into four groups: (i) IAI and IAH; (ii) IAI alone; (iii) IAH alone; and (iv) Control group. IAI model: cecal ligation and puncture for 48 h; IAH model: raised intra-abdominal pressure (IAP) of 20 mmHg for 4 h. Pathological changes in intestinal mucosa were confirmed by light and scanning electron microscopy. FITC-conjugated dextran (FITC-dextran) by gavage was used to measure intestinal mucosal permeability in plasma. Endotoxin, d-Lactate, and diamine oxidase (DAO) in plasma were measured to determine intestinal mucosal damage. Malonaldehyde (MDA), superoxide dismutase (SOD), and GSH in ileum tissues were measured to evaluate intestinal mucosal oxidation and reducing state. Histopathologic scores were significantly higher in the IAI and IAH group, followed by IAI alone, IAH alone, and the control group. FITC-dextran, d-Lactate, DAO, and endotoxin in plasma and MDA in ileum tissues had similar trends. GSH and SOD were significantly lowest the in IAI and IAH group. Occludin levels were lowest in the ileums of the IAI and IAH group. All differences were statistically significant (P-values <0.001). IAI combined with IAH aggravates damage of the intestinal mucosal barrier in a rabbit model. The combined effects were significantly more severe compared with a single factor. IAI combined with IAH should be prevented and treated effectively.

Methionine Metabolites in Patients With Sepsis.

OBJECTIVE: Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. METHODS: This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. RESULTS: Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P < .001; SAH: 99 [60-165] vs 35 [28-45] nM, P < .001). In contrast, plasma tHcy concentrations were lower in sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] µM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P < .001, respectively). Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. CONCLUSIONS: Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes. Further study is required to determine whether these abnormalities have pathophysiologic significance.

Therapeutic Role of Interleukin 22 in Experimental Intra-abdominal Klebsiella pneumoniae Infection in Mice.

Interleukin 22 (IL-22) is an IL-10-related cytokine produced by T helper 17 (Th17) cells and other immune cells that signals via IL-22 receptor alpha 1 (IL-22Ra1), which is expressed on epithelial tissues, as well as hepatocytes. IL-22 has been shown to have hepatoprotective effects that are mediated by signal transducer and activator of transcription 3 (STAT3) signaling. However, it is unclear whether IL-22 can directly regulate antimicrobial programs in the liver. To test this hypothesis, hepatocyte-specific IL-22Ra1 knockout (Il22Ra1(Hep-/-)) and Stat3 knockout (Stat3(Hep-/-)) mice were generated and subjected to intra-abdominal infection with Klebsiella pneumoniae, which results in liver injury and necrosis. We found that overexpression of IL-22 or therapeutic administration of recombinant IL-22 (rIL-22), given 2 h postinfection, significantly reduced the bacterial burden in both the liver and spleen. The antimicrobial activity of rIL-22 required hepatic Il22Ra1 and Stat3. Serum from rIL-22-treated mice showed potent bacteriostatic activity against K. pneumoniae, which was dependent on lipocalin 2 (LCN2). However, in vivo, rIL-22-induced antimicrobial activity was only partially reduced in LCN2-deficient mice. We found that rIL-22 also induced serum amyloid A2 (SAA2) and that SAA2 had anti-K. pneumoniae bactericidal activity in vitro. These results demonstrate that IL-22, through IL-22Ra1 and STAT3 singling, can induce intrinsic antimicrobial activity in the liver, which is due in part to LCN2 and SAA2. Therefore, IL-22 may be a useful adjunct in treating hepatic and intra-abdominal infections.

Tigecycline treatment causes a decrease in fibrinogen levels.

The objective of this study was to assess the impact of tigecycline treatment on coagulation parameters, specifically fibrinogen, in patients with severe infections. We examined 20 cases of tigecycline-treated patients with severe infections, including hospital-acquired pneumonia, complicated intra-abdominal infections, complicated skin and soft tissue infections, and bloodstream infections. We monitored the relative markers of coagulation and renal and liver function before, during, and after treatment. Fibrinogen (FIB) levels decreased significantly after the use of tigecycline and normalized after the cessation of treatment. FIB levels significantly decreased in the patients treated with the recommended dose or a higher treatment dose. The FIB levels decreased more in the higher-treatment-dose group. There was no difference in the decrease in FIB levels or the FIB level recovery by age. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were prolonged after tigecycline use. The TT decreased after the cessation of treatment, and the PT and APTT also decreased but not to a significant level. There was no change in platelet, alanine aminotransferase (ALT), or creatinine (Cr) levels associated with treatment. The use of tigecycline was associated with decreased FIB levels, which returned to normal after the cessation of treatment. A high-dose treatment group showed greater decreases in FIB levels than did patients treated with the recommended dose. The decline in FIB was not related to patient age. The use of tigecycline was associated with prolonged PT, APTT, and TT.

[Analysis of components of mesenteric lymph in rats with severe intraperitoneal infection].

OBJECTIVE: To investigate the components of mesenteric lymph of the rats with severe intraperitoneal infection, and inquire into the effect of intestinal lymphatic pathway in severe intraperitoneal infection. METHODS: Twenty-four male Wistar rats were randomly divided into two groups according to random number table method, namely model group and sham group with 12 rats in each group. The rat model of severe intraperitoneal infection was reproduced by injecting artificial gastric juice and E.coli intraperitoneally. Mesenteric lymph in both groups was collected 4 hours after the reproduction of the model, and white blood cells were counted and classified. The levels of endotoxin, alkaline phosphatase (AKP), lactate dehydrogenase (LDH), creatine kinase (CK), glutamine transferase (GST), protein and cytokines of mesenteric lymph were determined. RESULTS: Compared with the sham group, there was an increase in the neutrophil ratio in mesenteric lymph (0.167±0.004 vs. 0.610±0.006, t=33.520, P<0.001), however the percentage of both macrophages (0.009±0.001 vs. 0.020±0.004, t=-6.677, P<0.001) and lymphocytes (0.824±0.005 vs. 0.921±0.004, t=-31.471, P<0.001) was decreased in model group. Compared with sham group, the levels of endotoxin (0.346±0.022 kEU/L vs. 0.186±0.001 kEU/L, t=18.103, P<0.001), AKP [U (king unit): 13.97±5.55 vs. 3.76±0.18, t=4.503, P=0.006], LDH (2 827.45±1 940.32 U/L vs. 712.68±14.09 U/L, t=2.670, P=0.044), CK (2.19±1.21 kU/L vs. 0.70±0.01 kU/L, t=3.035, P=0.029), GST (12.33±6.53 kU/L vs. 1.36±0.39 kU/L, t=4.105, P=0.009) were all significantly elevated. The concentration of protein (4.40±0.48 g/L vs. 2.84±0.16 g/L, t=6.882, P=0.001), tumor necrosis factor-α (TNF-α: 499.39±76.36 ng/L vs. 180.90±70.98 ng/L, t=7.483, P<0.001), interleukin-6 (IL-6: 13.74±0.78 µg/L vs. -0.07±0.07 µg/L, t=52.972, P<0.001), intercellular adhesion molecule-1 (ICAM-1: 2 754.19±221.48 ng/L vs. 1 362.85±393.43 ng/L, t=6.891, P<0.001) and monocyte chemo-attractant protein-1 (MCP-1: 28.23±1.77 µg/L vs. 24.87±1.15 µg/L, t=3.561, P=0.007) and high mobility group protein-1 (HMGB-1: 1 392.78±572.42 ng/L vs. 564.17±21.32 ng/L, t=3.543, P=0.016) in mesenteric lymph in model group were significantly higher than those in sham group. CONCLUSIONS: Intestinal lymphatic pathway maybe the early pathway for the production of remote organ injury caused by severe intraperitoneal infection.

[Effect mechanism of NOD like receptor signaling pathway on intestinal mucosal barrier of rat during early phase of acute intra-abdominal infection].

OBJECTIVE: To initially investigate the expressing regularity and effect of enterocyte NOD like receptors on gut mucosal barrier during early phase of acute intra-abdominal infection. METHODS: Sprague-Dawley (SD) rats were randomly allocated into control group (n=6) and experimental group (n=24). Acute intra-abdominal infection model was induced by cecal ligation and puncture (CLP). The level of NOD2 and NOD like receptor 3 (NLRP3) mRNA expression in gut mucosa was determined using fluorescent polymerase chain reaction (PCR); the expression of caspase-1 and tight junction protein was determined by Western blotting; the activity of nuclear factor-ΚB (NF-ΚB) was determined by electrophoretic mobility shift assay (EMSA); the level of serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was determined by enzyme linked immunosorbent assay (ELISA). The dead cell percentage of enterocyte was observed by terminal deoxynucleotidyl transferase mediated nick end labeling, and the gut mucosal permeability using an in situ loop preparation of gut with fluorescence isothiocyanate-conjugated dextran was determined. RESULTS: NOD2 mRNA expression was quickly increased to a very high apex at 2 hours after operation, compared with the control group, the difference was statistically significant (75.50±13.03 vs. 1.00±0.00, P<0.01), and quickly descended at 6 hours, and then slowing descended. The expression of NLRP3 mRNA was decreased at 2 hours after the operation, then increased gradually, and peaked at 12 hours, which was significantly higher than that in control group (4.03±0.71 vs. 1.00±0.00,P<0.05). The level of caspase-1 was significantly higher than that in control group at 2 hours (3.56±0.14 vs. 2.10±0.11,P<0.01) and then gradually increased. The levels of Occludin, ZO-1 and Claudin-4 were obviously lowered than that in control group at 2-6 hours (2 hours Occludin: 7.24±1.13 vs. 12.72±1.34, 6 hours ZO-1: 0.47±0.09 vs. 1.57±0.17, 2 hours Claudin-4: 1.63±0.28 vs. 3.40±0.34, P<0.05 or P<0.01), and then all slowly decreased. The activity of NF-ΚB was quickly increased at 2 hours, obviously higher than that in control group (24.85±0.57 vs. 12.42±0.73, P<0.01), and then slowly decreased at a state of high expression. The expression of IL-6 in experimental group had a peak at 6 hours (compared with the control group, 3088.07±330.03 vs. 26.19±7.58,P<0.01), and then slowly decreased. The level of TNF-α was significantly higher than that in control group at 2 hours (110.75±19.18 vs. 7.86±3.58,P<0.01), and then gradually increased. The percentage of dead enterocyte was higher than that in control group with infection progress (0.12±0.02 vs. 0.03±0.01,P<0.05), and then gradually increased, so mucosal permeability was gradually increased too. Compared with the control group, the difference was statistically significant through 2 hours [glucosans: (35.75±4.66)% vs. (2.84±0.35)%, P<0.01]. The relevance analysis showed that NLRP3 have a little higher correlation with mucosal permeability and caspase-1 protein expression than other targets. Caspase-1 had a strong correlation with the percentage of dead cell, TNF-α and gut mucosal permeability. Gut mucosal permeability had highest correlation with the expression of caspase-1 protein. CONCLUSIONS: The data of our study suggested that NOD2 and NLRP3 take role in early phase of intra-abdominal infection, the huge wave of the expression level of NOD2 hinted that it was feed backed by some accurate mechanism in case of its express was too strong or too weak. The correlation of NLRP3, caspase-1, and percentage of dead cell imply they maybe have some extent of causation, and the percentage of dead cell in gut mucosa was as important as tight junction protein in maintaining the function of intestinal mucosal barrier.

Relationship between the clinical efficacy and AUC/MIC of intravenous ciprofloxacin in Japanese patients with intraabdominal infections.

The efficacy of fluoroquinolones (FQs) correlates with the pharmacokinetic/pharmacodynamic (PK-PD) parameter, AUC/MIC. To our knowledge, however, no prospective studies have reported the relationship between FQ efficacy and PK-PD parameters in intraabdominal infection; therefore, we prospectively investigated the relationship between the efficacy of intravenous ciprofloxacin (CPFX IV) and PK-PD parameters. The study included 16 patients diagnosed with peritonitis between 2006 and 2008: 14 patients infected with a single organism and 2 patients infected with more than one organism. Each patient was treated with CPFX IV (300 mg twice daily). The response rate was 56% (9 responders and 7 non-responders). Non-responders were infected with Escherichia coli, Pseudomonas aeruginosa, and Bacteroides fragilis (6 patients were infected with a single organism and 1 with more than one organism). Plasma drug concentrations were measured 1 h and 2 or 4 h after administration of CPFX IV. AUC for 24 h (AUC(0-24))/MIC values was calculated. The range of AUC(0-24)/MIC values in responders [95.3-3628.4 (geometric mean, 521.6)] was significantly different from that in non-responders [7.0-45.2 (geometric mean, 16.5)] (p = 0.001). The target AUC/MIC value of CPFX IV would be considered to be 45-95 in patients with peritonitis.

[The influence of sex hormones on human leukocyte antigen-DR, soluble myeloid cell receptor-1 and prognosis in patients with severe intra-abdominal infection].

OBJECTIVE: To evaluate the influence of serum estradiol, prolactin and testosterone levels on human leukocyte antigen-DR (HLA-DR), soluble myeloid cell receptor-1 (sTREM-1) and prognosis in patients with severe abdominal infection, in order to evaluate the clinical value of the above-mentioned sex hormones. METHODS: From July 10, 2009 to February 9, 2010, 73 cases with severe intra-abdominal infections hospitalized in surgical intensive care unit (ICU) of Tianjin Nankai Hospital were enrolled. Within 72 hours after enrollment, serum estradiol, prolactin and testosterone levels were detected by radioimmunoassay. Based on their levels, all the cases were divided into increased estradiol group (n=38) and non-increased estradiol group (n=35), increased prolactin group (n=28) and non-increased prolactin group (n=45), decreased testosterone group (n=33) and non-decreased testosterone group (n=40) respectively. In addition, HLA-DR (flow cytometry), as well as of sTREM-1 (enzyme linked immunosorbent assay), acute physiology and chronic health evaluation II (APACHEII) score, hospital days, the ICU length, hospital costs and 28 day mortality were recorded. RESULTS: Compared with non-increased estradiol group, HLA-DR in increased estradiol group decreased significantly [(61.22±22.39)% vs. (75.09±14.85)%], while sTREM-1 (ng/L) increased obviously (291.59±148.13 vs. 216.48±124.82), APACHEII score lowered dramatically (11.47±6.88 vs. 15.36±8.79), hospital costs (ten thousands) raised significantly (10.98±8.15 vs 6.25±3.51), ICU length (days) was much shorter (8.56±4.05 vs. 12.17±7.99), and 28 days mortality was significantly lowered (10.00% vs. 32.75%,P<0.05 or P<0.01). Compared with non-increased prolactin group, increased prolactin group had much lower HLA-DR levels [(61.19±21.50)% vs. (72.02±18.49)%], higher sTREM-1 levels (307.92±173.93 vs. 223.01±106.93), at the same time, their cost of hospitalization (7.75±3.52 vs. 11.36±8.24) and ICU stay length (9.14±3.15 vs. 13.24±2.16) were significantly lower (all P<0.05). Compared with non-decreased testosterone group, HLA-DR in decreased testosterone group increased significantly [(74.69±14.72)% vs. (62.24±22.54)%], while sTREM-1 decreased obviously (208.77±77.80 vs. 294.20±169.36), APACHEII score lowered dramatically (10.57±6.97 vs. 15.39±9.46), hospital costs decreased significantly (7.67±3.81 vs. 11.19±8.05), and 28 days mortality lowered significantly (0 vs. 30.14%, P<0.05 or P<0.01). CONCLUSIONS: In the early stage of severe intra-abdominal infection, estrogen, prolactin and testosterone levels had powerful influences on immune, inflammation, and prognosis, which may indicated a widespread clinical application.

Pharmacokinetics of beta-lactam antibiotics in patients with intra-abdominal disease: a structured review.

BACKGROUND AND PURPOSE: The objective of this structured review was to analyze critically the findings of pharmacokinetic studies of beta-lactam antibiotics in patients with intra-abdominal disease; that is, intra-abdominal infection (IAI) or previous abdominal surgery and determine the requirements for dosage modification in this population. METHODS: Data were identified by structured review of PUBMED from February 1983 to February 2011. All 14 articles reviewed described the pharmacokinetics of beta-lactam antibiotics in patients with intra-abdominal disease. RESULTS: Antibiotic classes included carbapenems, penicillins, cephalosporins, and monobactams. Possible physiological changes in these patients include development of abscesses, perforation, or ischemia of the bowel as well as intra-abdominal hypertension. These disorders may cause changes in antibiotic pharmacokinetics, including increased volume of distribution and faster drug clearance, both resulting in lower antibiotic concentrations. High inter-individual pharmacokinetic variability was common to each of the studies. CONCLUSION: Most of the available data demonstrate that drug volume of distribution can be increased significantly in the presence of intra-abdominal disease. Drug clearance is likely to vary in line with renal or hepatic function. Thus, dose optimization is important to prevent development of antibiotic resistance or therapeutic failure. However, further research is necessary to determine the clinical outcome of individualized dosing on the basis of pharmacokinetic/pharmacodynamic studies.

[Clinical and laboratory characteristics of the acetonemia syndrome in children with severe acute intestinal infection].

A total of 55 children suffering from acute intestinal infection severe in age from 3 months to 7 years; of these, 37 patients with atsetonemicheskim syndrome (AS). Found that the development AS in children with acute intestinal infections severe, aggravate the disease. In children with acute intestinal infection with the syndrome, the duration of atsetonemicheskim main symptoms of intoxication in the 1,2-1,5 times longer than those of children suffering from acute intestinal infection without atsetonemicheskogo syndrome.