ENDOGENOUS KLEBSIELLA PNEUMONIAE ENDOPHTHALMITIS IN NORTHERN CALIFORNIA.

PURPOSE: To report the clinical features, treatment modalities, and visual outcomes in 12 eyes with endogenous Klebsiella pneumoniae endophthalmitis (EKPE). METHODS: The medical records of all patients diagnosed with EKPE at Stanford Hospital (Palo Alto, CA) and Santa Clara Valley County Hospital (Santa Clara, CA) from January 2000 to March 2017 were retrospectively reviewed. RESULTS: A total of 10 patients (12 eyes) were diagnosed with EKPE. The median age at presentation was 56, 80% were male, and 30% were non-Asian. Presenting visual acuities ranged from 20/20 to no light perception. Of the 12 eyes 10 received a tap and injection (range, 1-33 injections per eye), 2 eyes underwent primary enucleation or evisceration, and 1 patient underwent pars plana vitrectomy after tap and injection. Final visual acuities ranged from no light perception (six eyes) to 20/300 or better (five eyes). Five patients eventually underwent evisceration or enucleation. All cases were associated with positive blood and/or vitreous cultures and had concurrent systemic infection. CONCLUSION: Endogenous Klebsiella pneumoniae endophthalmitis is a rare, but devastating, ocular infection. Most cases in this series resulted in light perception vision or worse, and almost half required enucleation or evisceration. In light of the virulence of EKPE, early diagnosis and treatment should be initiated in all suspected cases.

Monomicrobial Klebsiella pneumoniae necrotizing fasciitis: an emerging life-threatening entity.

BACKGROUND AND AIMS: Necrotizing fasciitis (NF) although rare, is a potentially fatal infection. The majority of cases are polymicrobial, although a recent surge has been reported in monomicrobial NF caused by Klebsiella pneumoniae (KP-NF). KP-NF recently accounted for an average of 16% among all pathogens, with highest mortality rate of 60%. This review discusses the important aspects of KP-NF with additional notes on the implications of multidrug resistant infections. SOURCES: The literature was searched using PubMed. Klebsiella pneumoniae isolated monomicrobially in NF cases was used as the selection criteria. CONTENT: KP-NF predominates in East Asia with the majority of cases reported from Taiwan alone. Reports from the Western hemisphere are also gradually rising. This infection has invariably presented with underlying predisposing factors occurring mostly in individuals with compromised host immunity. Diabetes, chronic liver disease, and instrumentation are important risk factors. With haematogenous spread more common, multifocal involvement via metastasis is reported. Clinical presentations are usually aggressive with rapid progression despite antimicrobial therapy. It may even present with severe sepsis. Clinicians must be aware of the differential diagnosis of such severe presentations. Emergency surgical explorations and microbiological investigations clinch the diagnosis. Outcomes are not favourable, with a high mortality rate of 40% even after appropriate interventions. Nosocomial KP-NF cases are more fulminant and multidrug resistant with even higher mortality rates (approx. 70%). IMPLICATIONS: KP-NF with its virulent course and high mortality, is an emerging life threat. Clinicians must be aware of its key features. Further comprehensive studies are needed for better insights into the spectrum of this fatal infection.

Inhibition of nitric oxide production reverses diabetes-induced Kupffer cell activation and Klebsiella pneumonia liver translocation.

Klebsiella pneumoniae (KP) is the most common pathogen of pyogenic liver abscess in East and Southeast Asia and diabetes mellitus (DM) is a major risk factor. The effect and mechanism of diabetes on KP liver abscess was examined in streptozotocin-induced diabetic mice and Akita mice (C57BL/6J-Ins2Akita). KP translocation to liver and plasma alaine transaminase levels were increased and liver clearance of KP was decreased in DM mice. Diabetic mice exhibited overgrowth of Enterococcus as well as E.coli and decreased lactobacilli/bifidas growth in intestine, increased intestinal iNOS protein and nitrite levels in portal vein, and increased IL-1ß and TNF-α expression of Kupffer cells. Fructooligosaccharides (FOS) or dead L. salivarius (dLac) supplementation reversed diabetes-induced enteric dysbiosis, NO levels in portal vein, and KP translocation to liver. L-NAME treatment decreased intestinal iNOS protein expression as well as Kupffer cell activation and increased liver clearance of KP in DM mice. Dead E.coli (2×108 CFU/ml) feeding for one week induced iNOS and TLR4 expression of intestine in germ-free (GF) mice. Dead bacteria feeding induced IL-1ß and TNF-α expression of Kupffer cells in GF mice but not in GF TLR4-/- mice. In conclusion, balance of intestinal microflora is important for preventing intestinal iNOS expression, Kupffer cell activation, and KP liver translocation in diabetes. Reversal of diabetes-induced enteric dysbiosis with FOS or dead L. salivarius decreases diabetes-induced intestinal iNOS expression and KP liver translocation. Diabetes induces Kupffer cell activation and KP liver translocation through enteric dysbiosis and nitric oxide production.

More Than Meets the Eye: Klebsiella pneumoniae Invasive Liver Abscess Syndrome Presenting with Endophthalmitis.

BACKGROUND: Endophthalmitis is a feared complication of pyogenic liver abscesses caused by hypervirulent Klebsiella pneumoniae strains. First described in East Asia in the 1980s, this invasive syndrome is only recently emerging in Europe and America. CASE REPORT: We describe an 84-year-old man who presented to the emergency department with fever, orbital cellulitis, and bilateral visual loss. Although the patient had no overt abdominal symptoms, computed tomography scan revealed a pyogenic liver abscess. Blood cultures were positive for K. pneumoniae. Initial treatment consisted of intravenous ceftriaxone and intravitreal ceftazidime. A unilateral vitrectomy was performed. The patient survived with severe visual sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: K. pneumoniae pyogenic liver abscess with metastatic endophthalmitis is a relatively new syndrome that should be considered in patients presenting with acute vision loss who appear septic, with or without abdominal complaints. Early recognition prohibits delays in lifesaving treatment.

The mito-DAMP cardiolipin blocks IL-10 production causing persistent inflammation during bacterial pneumonia.

Bacterial pneumonia is a significant healthcare burden worldwide. Failure to resolve inflammation after infection precipitates lung injury and an increase in morbidity and mortality. Gram-negative bacteria are common in pneumonia and increased levels of the mito-damage-associated molecular pattern (DAMP) cardiolipin can be detected in the lungs. Here we show that mice infected with Klebsiella pneumoniae develop lung injury with accumulation of cardiolipin. Cardiolipin inhibits resolution of inflammation by suppressing production of anti-inflammatory IL-10 by lung CD11b+Ly6GintLy6CloF4/80+ cells. Cardiolipin induces PPARγ SUMOylation, which causes recruitment of a repressive NCOR/HDAC3 complex to the IL-10 promoter, but not the TNF promoter, thereby tipping the balance towards inflammation rather than resolution. Inhibition of HDAC activity by sodium butyrate enhances recruitment of acetylated histone 3 to the IL-10 promoter and increases the concentration of IL-10 in the lungs. These findings identify a mechanism of persistent inflammation during pneumonia and indicate the potential of HDAC inhibition as a therapy.

Hemodialysis Catheter Heat Transfer for Biofilm Prevention and Treatment.

Central line-associated bloodstream infections (CLABSIs) are not easily treated, and many catheters (e.g., hemodialysis catheters) are not easily replaced. Biofilms (the source of infection) on catheter surfaces are notoriously difficult to eradicate. We have recently demonstrated that modest elevations of temperature lead to increased staphylococcal susceptibility to vancomycin and significantly soften the biofilm matrix. In this study, using a combination of microbiological, computational, and experimental studies, we demonstrate the efficacy, feasibility, and safety of using heat as an adjuvant treatment for infected hemodialysis catheters. Specifically, we show that treating with heat in the presence of antibiotics led to additive killing of Staphylococcus epidermidis with similar trends seen for Staphylococcus aureus and Klebsiella pneumoniae. The magnitude of temperature elevation required is relatively modest (45-50°C) and similar to that used as an adjuvant to traditional cancer therapy. Using a custom-designed benchtop model of a hemodialysis catheter, positioned with tip in the human vena cava as well as computational fluid dynamic simulations, we demonstrate that these temperature elevations are likely achievable in situ with minimal increased in overall blood temperature.

SPLUNC1/BPIFA1 contributes to pulmonary host defense against Klebsiella pneumoniae respiratory infection.

Epithelial host defense proteins comprise a critical component of the pulmonary innate immune response to infection. The short palate, lung, nasal epithelium clone (PLUNC) 1 (SPLUNC1) protein is a member of the bactericidal/permeability-increasing (BPI) fold-containing (BPIF) protein family, sharing structural similarities with BPI-like proteins. SPLUNC1 is a 25 kDa secretory protein that is expressed in nasal, oropharyngeal, and lung epithelia, and has been implicated in airway host defense against Pseudomonas aeruginosa and other organisms. SPLUNC1 is reported to have surfactant properties, which may contribute to anti-biofilm defenses. The objective of this study was to assess the importance of SPLUNC1 surfactant activity in airway epithelial secretions and to explore its biological relevance in the context of a bacterial infection model. Using cultured airway epithelia, we confirmed that SPLUNC1 is critically important for maintenance of low surface tension in airway fluids. Furthermore, we demonstrated that recombinant SPLUNC1 (rSPLUNC1) significantly inhibited Klebsiella pneumoniae biofilm formation on airway epithelia. We subsequently found that Splunc1(-/-) mice were significantly more susceptible to infection with K. pneumoniae, confirming the likely in vivo relevance of this anti-biofilm effect. Our data indicate that SPLUNC1 is a crucial component of mucosal innate immune defense against pulmonary infection by a relevant airway pathogen, and provide further support for the novel hypothesis that SPLUNC1 protein prevents bacterial biofilm formation through its ability to modulate surface tension of airway fluids.

A rat model for stable chronic obstructive pulmonary disease induced by cigarette smoke inhalation and repetitive bacterial infection.

To develop a stable chronic obstructive pulmonary disease (COPD) model in rats. Sprague-Dawley rats were treated with cigarette-smoke inhalation (CSI) for 12 weeks, repetitive bacterial infection (RBI) for 8 weeks, or the combination of the two (CCR) for 12 weeks and followed up for the additional 20 weeks. Tidal volume (V(T)), peak expiratory flow (PEF) and 50% V(T) expiratory flow (EF(50)), histological changes in the lungs, and levels of the cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-8, and IL-10 in serum and bronchial alveolar lavage fluid (BALF) were examined at intervals during the 32 week study period. The right ventricular hypertrophy index (RVHI) was also determined at the same times. V(T), PEF, and EF(50) were decreased in rats with COPD compared to the control. The expression of TNF-α, IL-8 and IL-10 increased in both serum and BALF with a similar trend. Bronchiole and arteriole wall thickness and the degree of bronchiole stenosis and alveolar size increased in COPD rats. RVHI was reduced gradually following the treatment. All of these changes were more pronounced in the CCR-treatment group than in the other groups. Our results have shown that CSI or RBI alone can induce COPD in rats, but that the combination of CSI with RBI induces a stable COPD that has more similarity to complications seen in patients with COPD. This combination may therefore provide a more appropriate model for study of human COPD.

Gonadal hormones and oxidative stress interaction differentially affects survival of male and female mice after lung Klebsiella pneumoniae infection.

Survival of mice after Klebsiella pneumoniae infection and phagocytosis by alveolar macrophages (AMs), in the presence or absence of ozone (O(3)) exposure prior to infection, is sex dependent. The objective of this work was to study the role of gonadal hormones, 5α-dihydrotestosterone (DHT) and 17ß-estradiol (E(2)), on mouse survival after filtered air (FA) or O(3) exposure. Gonadectomized female (G×F) and male (G×M) mice implanted with control or hormone pellets (DHT in G×F, or E(2) in G×M), exposed to O(3) (2 ppm, 3h) or FA, and infected with K. pneumoniae were monitored for survival. Survival in G×F was identical after FA or O(3) exposure; in G×M O(3) exposure resulted in lower survival compared to FA. In O(3)-exposed females, gonadectomy resulted in increased survival compared to intact females or to G×M+E(2). A similar effect was observed in G×F+DHT. The combined negative effect of oxidative stress and hormone on survival was higher for E(2). Gonadectomy eliminated (females) or minimized (males) the previously observed sex differences in survival in response to oxidative stress, and hormone treatment restored them. These findings indicate that gonadal hormones and/or oxidative stress have a significant effect on mouse survival.

Pathogen-induced heart rate changes associated with cholinergic nervous system activation.

The autonomic nervous system plays a central role in regulation of host defense and in physiological responses to sepsis, including changes in heart rate and heart rate variability. The cholinergic anti-inflammatory response, whereby infection triggers vagal efferent signals that dampen production of proinflammatory cytokines, would be predicted to result in increased vagal signaling to the heart and increased heart rate variability. In fact, decreased heart rate variability is widely described in humans with sepsis. Our studies elucidate this apparent paradox by showing that mice injected with pathogens demonstrate transient bradyarrhythmias of vagal origin in a background of decreased heart rate variability (HRV). Intraperitoneal injection of a large inoculum of Gram-positive or Gram-negative bacteria or Candida albicans rapidly induced bradyarrhythmias of sinus and AV nodal block, characteristic of cardiac vagal firing and dramatically increased short-term HRV. These pathogen-induced bradycardias were immediately terminated by atropine, an antagonist of muscarinic cholinergic receptors, demonstrating the role of vagal efferent signaling in this response. Vagal afferent signaling following pathogen injection was demonstrated by intense nuclear c-Fos activity in neurons of the vagal sensory ganglia and brain stem. Surprisingly, pathogen-induced bradycardia demonstrated rapid and prolonged desensitization and did not recur on repeat injection of the same organism 3 h or 3 days after the initial exposure. After recovery from the initial bradycardia, depressed heart rate variability developed in some mice and was correlated with elevated plasma cytokine levels and mortality. Our findings of decreased HRV and transient heart rate decelerations in infected mice are similar to heart rate changes described by our group in preterm neonates with sepsis. Pathogen sensing and signaling via the vagus nerve, and the desensitization of this response, may account for periods of both increased and decreased heart rate variability in sepsis.

Extended-spectrum beta-lactamase-producing phenotype signifies a poor prognosis for patients with cefpodoxime-resistant Escherichia coli or Klebsiella pneumoniae bacteremia.

BACKGROUND AND PURPOSE: Bloodstream infections caused by multidrug-resistant Enterobacteriaceae are a major concern. This study explored the clinical impact of extended-spectrum beta-lactamase (ESBL) production among cefpodoxime-resistant Escherichia coli and Klebsiella pneumoniae bacteremia. METHODS: The medical charts and microbiological results of patients with cefpodoxime-resistant E. coli or K. pneumoniae bacteremia in a tertiary hospital in southern Taiwan between June 2003 and December 2006 were retrospectively reviewed. The clinical characteristics, medical histories, and clinical outcomes were evaluated. ESBL production was indicated by the double-disk synergy test. RESULTS: 278 episodes of bacteremia caused by cefpodoxime-resistant K. pneumoniae or E. coli were identified, of which 115 (41%) were ESBL producing. Compared with non-ESBL-producing bacteremia, bacteremic episodes caused by ESBL producers were less often community acquired (4.3% vs 26.4%; p < 0.001). Underlying diabetes mellitus (48.7% vs 35.0%; p = 0.02), liver cirrhosis (22.6% vs 11.7%; p = 0.02), or uremia (21.7% vs 3.7%; p < 0.001) were more common in ESBL-producing bacteremia. In contrast, solid tumors were more frequent in non-ESBL-producing bacteremia (44.8% vs 27.8%; p = 0.004). Overall, patients with ESBL-producing bacteremia had higher disease severity indicated by a Pittsburgh bacteremia score > or = 4, longer duration of hospital stay (51.1 days vs 31.9 days; p = 0.007), more admission to intensive care units (19.1% vs 8.0%; p = 0.006), and a higher mortality rate at 28 days (34.8% vs 23.9%; p = 0.03). CONCLUSIONS: ESBL production signifies a poor clinical outcome for patients with bacteremia caused by cefpodoxime-resistant E. coli or K. pneumoniae.

Correlation between time to positivity of blood cultures with clinical presentation and outcomes in patients with Klebsiella pneumoniae bacteraemia: prospective cohort study.

Time to positivity (TTP) of blood cultures in patients with bacteraemia is considered to be a predictor of outcome for some bacterial species. Two hundred and thirty-one patients with Klebsiella pneumoniae monomicrobial bacteraemia at a hospital from 1 January to 31 December 2007 were prospectively enrolled. TTP <7 h (46 patients, 19.9%) was associated with a higher Pittsburg bacteraemia score (6.2 +/- 5.5 vs. 3.7 +/- 4.3, p 0.002), fewer non-fatal diseases by the McCabe classification (39.1% vs. 64.9%, p 0.002), a higher percentage of patients with liver cirrhosis, active malignancy, and chemotherapy within 3 months (28.3% vs. 11.9%, p 0.007; 28.3% vs. 14.6%, p 0.031; 23.9% vs. 5.4%, p <0.001), more primary bacteraemia (45.7% vs. 22.2%, p 0.002), and a higher 30-day mortality rate (47.8% vs. 21.1%, p <0.001). Risk factors for 30-day mortality in the univariate analysis included higher Pittsburg bacteraemia score (5.8 +/- 5.3 vs. 3.7 +/- 4.3, p 0.002), primary bacteraemia (41.0% vs. 21.8%, p 0.004), TTP <7 h (36.1% vs. 14.1%, p <0.001), and the presence of active malignancy (29.5% vs. 12.9%, p 0.004). In the multivariate analysis, higher Pittsburg bacteraemia score (OR 1.07; 95% CI 1.01-1.14), TTP <7 h (OR 2.46; 95% CI 1.20-5.05) and active malignancy (OR 2.21; 95% CI 1.03-4.73) were the significant factors associated with 30-day mortality. In the Kaplan-Meier survival curve, short TTP was significantly associated with mortality at all time-points after admission. TTP of blood cultures, interpreted with a cut-off point of <7 h, in patients with K. pneumoniae bacteraemia can provide useful prognostic information.

Community-acquired Klebsiella pneumoniae complicated skin and soft-tissue infections of extremities: emphasis on cirrhotic patients and gas formation.

BACKGROUND: Klebsiella pneumoniae was rarely reported to cause complicated skin and soft tissue infections (cSSTIs). Our study was to delineate clinical characteristics and outcome of cSSTIs involving extremities caused by K. pneumoniae. PATIENTS AND METHODS: Adult patients aged 16 years or more with community-acquired cSSTIs, which involved the extremities and were caused by four common aerobic pathogens at a medical center in southern Taiwan during a 54-month period, were reviewed. RESULTS: Of 76 cases enrolled, Staphylococcus aureus was the most common pathogen (52 cases, 68%), followed by K. pneumoniae (16, 21%), beta-hemolytic streptococci (5, 7%), and Escherichia coli (3, 4%). Forty-six (61%) had underlying conditions, and diabetes mellitus was most common among K. pneumoniae and non-K. pneumoniae groups (63% and 45%, respectively). Compared to patients with cSSTIs caused by other bacteria, those with K. pneumoniae cSSTIs were predominantly male, more often had liver cirrhosis, malignant neoplasm and alcoholism. In addition, they were more likely to have fever, shock, bacteremia, gas formation, pyomyositis, metastatic infections, as well as longer durations of hospitalization. Using multivariate analysis, liver cirrhosis (adjusted odds ratio [aOR] 12.5, 95% confidence interval [CI] 2.0-79.1, p = 0.007) and male gender (aOR 11.5, 95% CI 1.1-116.8, p = 0.039) were significantly associated with K. pneumoniae cSSTIs. CONCLUSIONS: We highlight the role of K. pneumoniae in Taiwanese patients with cSSTIs involving extremities, and its potential for gas and pus formation, and metastatic infections. Empiric antimicrobial coverage of K. pneumoniae and close monitoring of metastatic infections are mandatory for patients with risk factors.

Infection induces a positive acute phase apolipoprotein E response from a negative acute phase gene: role of hepatic LDL receptors.

Apolipoprotein E (apoE) plays important roles in lipid homeostasis, anti-inflammation, and host defense. Since tissue apoE mRNA levels have been reported to decrease during inflammatory responses, we were surprised to find that plasma apoE levels were significantly elevated during septic infections in both humans and mice. This apparent paradox was also observed during lipopolysaccharide-induced acute inflammation in mice: plasma levels of apoE increased up to 4-fold despite sharply decreased apoE gene expression in the liver, macrophages, and extrahepatic tissues. We hypothesized that apoE levels were augmented by decreased plasma clearance. Our analysis revealed that apoE associated principally with HDL in mice and that apoE was cleared from the circulation principally via LDL receptors. The acute inflammatory response decreased LDL receptor expression in the liver and significantly reduced the rate of apoE clearance. In contrast, the same inflammatory stimuli increased LDL receptor expression in macrophages. Our results define a novel acute phase mechanism that increases circulating apoE levels as apoE production decreases. Diminished hepatic LDL receptor expression may thus cooperate with elevated LDL receptor expression in macrophages to facilitate the forward transport of apoE and its associated lipids to these key defense cells.

Sex differences in the impact of ozone on survival and alveolar macrophage function of mice after Klebsiella pneumoniae infection.

BACKGROUND: Sex differences have been described in a number of pulmonary diseases. However, the impact of ozone exposure followed by pneumonia infection on sex-related survival and macrophage function have not been reported. The purpose of this study was to determine whether ozone exposure differentially affects: 1) survival of male and female mice infected with Klebsiella pneumoniae, and 2) the phagocytic ability of macrophages from these mice. METHODS: Male and female C57BL/6 mice were exposed to O3 or to filtered air (FA) (control) and then infected intratracheally with K. pneumoniae bacteria. Survival was monitored over a 14-day period, and the ability of alveolar macrophages to phagocytize the pathogen in vivo was investigated after 1 h. RESULTS: 1) Both male and female mice exposed to O3 are significantly more susceptible to K. pneumoniae infection than mice treated with FA; 2) although females appeared to be more resistant to K. pneumoniae than males, O3 exposure significantly increased the susceptibility of females to K. pneumoniae infection to a greater degree than males; 3) alveolar macrophages from O3-exposed male and female mice have impaired phagocytic ability compared to macrophages from FA-exposed mice; and 4) the O3-dependent reduction in phagocytic ability is greater in female mice. CONCLUSION: O3 exposure reduces the ability of mice to survive K. pneumoniae infection and the reduced phagocytic ability of alveolar macrophages may be one of the contributing factors. Both events are significantly more pronounced in female mice following exposure to the environmental pollutant, ozone.

Transgenic tissue-type plasminogen activator expression improves host defense during Klebsiella pneumonia.

BACKGROUND: Severe pneumonia is associated with a local inhibition of fibrinolysis in the lung as reflected by strongly reduced pulmonary plasminogen activator activity. OBJECTIVES: To study the effect of elevation of local plasminogen activator activity during pneumonia caused by the common respiratory pathogen Klebsiella pneumoniae. METHODS: Female C57Bl/6 mice were inoculated intranasally with a replication-defective adenoviral vector expressing human tissue-type plasminogen activator or a control vector 24 h before intranasal infection with K. pneumoniae. RESULTS: Mice infected with Klebsiella via the airways developed overt pneumonia, which was accompanied by a downregulation of pulmonary tissue-type plasminogen activator levels at protein and mRNA levels. Pulmonary overexpression of human tissue-type plasminogen activator resulted in increased fibrinolytic activity in the lungs during pneumonia, as indicated by higher D-dimer levels and reduced fibrin deposition. Interestingly, overexpression of tissue-type plasminogen activator markedly improved host defense against pneumonia: mice treated with the tissue-type plasminogen activator vector displayed less bacterial growth and dissemination, attenuated distant organ injury and a reduced mortality. CONCLUSIONS: These data demonstrate that local elevation of plasminogen activator activity in the lungs improves host defense against severe gram-negative pneumonia and sepsis.

Clinical implications and risk factors of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae infection in children: a case-control retrospective study in a medical center in southern Taiwan.

BACKGROUND AND PURPOSE: Infections caused by extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacilli constitute a growing problem worldwide. However, studies focusing on children are limited. METHODS: We have observed an increase in cases of ESBL-producing Klebsiella pneumoniae (ESBL-KP) infections in the past 6 years in our hospital in southern Taiwan. Using a case-control study design, we compared the clinical characteristics between 54 patients infected by ESBL-KP and 54 frequency-matched controls infected by non-ESBL-producing isolates. RESULTS: Risk factors associated with the infection of ESBL-KP were mainly longer pre-infection hospital stay and recent antibiotic exposure (within 30 days before the episode). Other potential risk factors included recent surgery, the application of mechanical ventilation, nasogastric tubes and central venous catheter insertion. ESBL-KP-related infection cases had a longer hospital stay than controls, and also had a higher mortality rate, although not significantly so. CONCLUSIONS: Recent antibiotic exposure was by far the most important predisposing factor associated with infection of ESBL-KP. Unnecessary antibiotic use should be avoided both in the hospital and community, especially ceftazidime, vancomycin/teicoplanin, aminoglycosides and ampicillin. In our study, carbapenem antibiotics remained the most active drugs against ESBL-KP in pediatric patients, while flomoxef and ciprofloxacin were suitable alternative choices.

Subcutaneous gas tensions closely track ileal mucosal gas tensions in a model of endotoxaemia without anaerobism.

OBJECTIVE: Few comparative data exist on the responses of the subcutaneous and splanchnic circulations to evolving endotoxic shock. We therefore compared continuous subcutaneous pO(2) (pO(2sc)) and pCO(2) (pCO(2sc)) with simultaneous continuous gut luminal pCO(2) (pCO(2gi)) in an animal model of endotoxaemia and examined whether changes in gas tensions track tissue energy charge (EC). DESIGN: Prospective observational study. SUBJECTS: Fourteen anaesthetized rats, 7 controls and 7 experimental. INTERVENTIONS: Controls were injected with saline, the experimental group with 20 mg/kg Klebsiella endotoxin. pCO(2sc), pO(2sc), and pCO(2gi) were measured continuously. Plasma lactate concentrations were measured at defined periods during the study. After 2 h ileal segments were snap frozen and assayed for tissue EC. MEASUREMENTS AND RESULTS: Endotoxaemia resulted in a significant decrease in mean arterial blood pressure (132+/-9 to 71+/-20 mmHg) and pO(2sc) (71+/-23 to 33+/-22 torr) and a significant increase in pCO(2gi) (58+/-10 to 90+/-20 torr) and pCO(2sc) (56+/-6 to 81+/-25 torr). During endotoxaemia pCO(2gi) was directly correlated with pCO(2sc) (R (2)=0.5) and inversely correlated with pO(2sc) (R (2)=0.63). Plasma lactate concentrations were significantly elevated from baseline in the endotoxin limb. The mean EC was not significantly different in the two groups. CONCLUSIONS: Both subcutaneous tissue gas tensions and intestinal luminal carbon dioxide tensions are rapidly responsive during evolving hypodynamic endotoxic shock. Alterations in tissue gas tensions were not associated with dysoxia.