Development Of Bacterial Infections Research Articles

Antibiotic Prophylaxis in Patients with Cirrhosis

A major cause of morbidity and mortality among patients with cirrhosis, especially decompensated cirrhosis, is the development of bacterial infections.

Antibiotic prophylaxis in cirrhosis: Good and bad.

Patients with cirrhosis, particularly those with decompensated cirrhosis, are at increased risk of bacterial infections that may further precipitate other liver decompensations including acute-on-chronic liver failure. Infections constitute the main cause of death in patients with advanced cirrhosis, and strategies to prevent them are essential. The main current strategy is the use of prophylactic antibiotics targeted at specific subpopulations at high risk of infection: prior episode of spontaneous bacterial peritonitis, upper gastrointestinal bleeding, and low-protein ascites with associated poor liver function. Antibiotic prophylaxis effectively prevents not only the development of bacterial infections in all these indications but also further decompensation (variceal bleeding, hepatorenal syndrome) and improves survival. However, antibiotic prophylaxis is also associated with a clinically relevant and increasing drawback, the development of infections due to multidrug-resistant organisms. Several strategies have been suggested to balance the risks and benefits of antibiotic prophylaxis. Antibiotic stewardship principles such as the restriction of antibiotic prophylaxis to subpopulations at a very high risk for infection, the avoidance of antibiotic overuse, and early deescalation policies are key to achieve this balance; nonantibiotic prophylactic measures such as probiotics, prokinetics, bile acids, statins, and hematopoietic growth factors could also contribute to ameliorate the development and spread of multidrug-resistant bacteria in cirrhosis. (Hepatology 2016;63:2019-2031).

LBP526 - Prevalence of Rectal Colonization by MDR Bacteria and Relationship with Bacterial Infection Development in Patients Admitted to a Liver ICU

LBP526 - Prevalence of Rectal Colonization by MDR Bacteria and Relationship with Bacterial Infection Development in Patients Admitted to a Liver ICU

Host Antimicrobial Peptides in Bacterial Homeostasis and Pathogenesis of Disease.

Innate immune responses function as a first line of host defense against the development of bacterial infection, and in some cases to preserve the sterility of privileged sites in the human host. Bacteria that enter these sites must counter host responses for colonization. From the host’s perspective, the innate immune system works expeditiously to minimize the bacterial threat before colonization and subsequent dysbiosis. The multifactorial nature of disease further challenges predictions of how each independent variable influences bacterial pathogenesis. From bacterial colonization to infection and through disease, the microenvironments of the host are in constant flux as bacterial and host factors contribute to changes at the host-pathogen interface, with the host attempting to eradicate bacteria and the bacteria fighting to maintain residency. A key component of this innate host response towards bacterial infection is the production of antimicrobial peptides (AMPs). As an early component of the host response, AMPs modulate bacterial load and prevent establishment of infection. Under quiescent conditions, some AMPs are constitutively expressed by the epithelium. Bacterial infection can subsequently induce production of other AMPs in an effort to maintain sterility, or to restrict colonization. As demonstrated in various studies, the absence of a single AMP can influence pathogenesis, highlighting the importance of AMP concentration in maintaining homeostasis. Yet, AMPs can increase bacterial virulence through the co-opting of the peptides or alteration of bacterial virulence gene expression. Further, bacterial factors used to subvert AMPs can modify host microenvironments and alter colonization of the residential flora that principally maintain homeostasis. Thus, the dynamic interplay between host defense peptides and bacterial factors produced to quell peptide activity play a critical role in the progression and outcome of disease.

The abandoned controversy surrounding universal white blood cell reduction.

The abandoned controversy surrounding universal white blood cell reduction.

Primary prophylaxis with ciprofloxacin in cirrhotic patients with ascites: a randomized, double blind study

Introduction and aim. There is scarce information about primary prophylaxis in cirrhotic patients. The aim was to assess the efficacy of ciprofloxacin for primary prophylaxis for bacterial infections in patients with cirrhosis of the liver and ascites.Material and methods. A randomized, double-blind placebo-controlled clinical trial was conduced. Patients were randomized to receive oral ciprofloxacin 500 mg/day or placebo for one month. A basal evaluation and repeated assessments at 4, 6, 12, 18, and 24 weeks afterwards, or whenever a primary endpoint occurred were done. Statistical analysis: probability curves were constructed with the Kaplan-Meier method and compared by the log-rank test.Results. 95 patients were randomized to ciprofloxacin group (n = 49; 51.6%) and placebo group (n = 46; 48.4%). Six-teen (32.6%) patients in the ciprofloxacin group developed bacterial infections and thirteen (28.2%) patients developed bacterial infections in the placebo group (p = NS). The probability to remain free of bacterial infections did not reach statistical significance (p = 0.38). Probability of survival at 24 weeks was 91% in placebo group and 98% in the ciprofloxacin group (p = 0.28). The absolute risk reduction was 5%, the relative risk reduction was 6% and the NNT was 20 patients.Conclusion. Primary prophylaxis with ciprofloxacin for one month in cirrhotic patients with ascites who do not have a currently accepted indication, did not show a preventive effect on the development of bacterial infections at one month follow-up. Moreover in women could increases the odds for UTI. The administration of ciprofloxacin seemed to decrease the risk of mortality.

Role of Portal Hypertension in Prediction of Bacterial Infection in Decompensated Cirrhosis

Background: Bacterial infection in cirrhotic patients is a fatal complication. The high incidence of bacterial infections in those patients may be related to several alterations in the defensive mechanisms against infections and increased intestinal permeability with bacterial translocation. Aim: To evaluate the role of portal hypertension (PH) in predicting the occurrence of bacterial infections in decompensated cirrhosis. Patients and Methods: In this retrospective cohort study, 99 patients—56 males and 43 females, with decompensated liver cirrhosis were included. Diagnosis of liver cirrhosis was based on clinical, laboratory and ultrasonographic examinations. Patients were classified according to the presence of bacterial infection into patients with infection—Group 1, and those without infection—Group 2. Laboratory, abdominal US and upper endoscopic data for all patients were collected. Logistic regression analysis was done to detect the independent factors for prediction of bacterial infection. Results: The mean age of patients was 50.5 ± 14.2 years. Bacterial infection was found in 41 patients (41.4%) and no infection in 58 patients (58.6%). Infected patients showed statistically significant higher values in the level of bilirubin, PT and Child-Pugh score (P value = 0.000) and lower values in the level of albumin, total serum protein and PC than those without infection (P value = 0.006, 0.000 and 0.000 respectively). Portal vein diameter (PVD) and splenic diameter (SD) showed statistically significant higher values in infected patients than in those without infection (P value = 0.028 and 0.000 respectively), also infection was more significantly prevalent in patients with varices than those without varices (P value = 0.000). The independent predictors for bacterial infection were: the age, total serum bilirubin, serum albumin, PT, PC, child score, PVD, SD and the presence of varices. Conclusion: Presence of varices (as a complication of PH) is an independent risk factor for the development of bacterial infection in decompensated cirrhotic patients and reduction of PH by any way could decrease this fatal complication.

Cirrhosis but not neutropenia is associated with the development of infection in patients with chronic hepatitis C undergoing treatment with pegylated interferon‐alpha and ribavirin

Peginterferon-alpha (PegIFNa) frequently causes neutropenia, mainly due to bone marrow suppression. The aim of this study was to explore factors that are associated with infections during antiviral treatment. We analysed data from 275 chronic hepatitis C (CHC) patients with compensated liver disease who underwent 318 courses of PegIFNa and ribavirin. Neutropenia was defined as neutrophils <1000 cells/μL. Mean leucocytes count significantly decreased from baseline to treatment nadir (7081 ± 2182 vs 3293 ± 1331 cells/μL, P < 0.001), while neutropenia was observed in 32% during treatment. Thirty-one infections were observed. The incidence rate for infection was assessed at 1.46 infections per 100 person-months of therapy. The hazard rate for infection did not correlate with the neutrophils' nadir or the decrease in white blood cells. In multivariate Cox's regression analysis, cirrhosis was the only factor that was significantly associated with the occurrence of infection. Our data show that the development of bacterial infections during treatment with PegIFNa and ribavirin in patients with compensated CHC is not associated with reduction or the nadir of white cells or neutrophil counts. Baseline cirrhosis is the only factor related with infection during treatment. The common practice of dose adjustment or discontinuation of interferon should be revised; careful assessment of liver damage before therapy and close monitoring during therapy are essential in all patients receiving interferon-based regimes, to minimize the detrimental consequences of infections.

Raised sympathetic activity and blood ammonia could increase sensitivity to infections in patients with cirrhosis and refractory ascites who are using beta-blockers

We read with interest the study by Sersté et al. who found a negative impact of beta-blockers on survival in patients with cirrhosis and refractory ascites.1 Interestingly, 79.5% of patients with a specified cause of death died of sepsis, suggesting an association between chronic use of beta-blockers and development of bacterial infections, yet the authors did not provide an explanation. We suggest that raised blood norepinephrine (NE) and ammonia levels could contribute to increased vulnerability to bacterial infections in patients with refractory ascites who are taking beta-blockers. Circulating NE levels can be increased in cirrhosis due to reduced effective blood volume, impaired liver metabolism, portosystemic shunts, and propranolol treatment.2, 3 Patients with refractory ascites are commonly characterized by markedly increased plasma NE levels.2 High NE levels have been shown to suppress neutrophil chemotaxis4 and phagocytosis5 as well as to inhibit macrophage proliferation and promote their apoptosis.6 In the study of Sersté et al., beta-blocker–treated patients had worse liver function and systemic hemodynamics, which together with the presence of collaterals and propranolol treatment could result in higher NE concentration compared to the nontreatment group. Blood ammonia can also impair neutrophil phagocytosing function in cirrhosis7 and increases significantly with the grade of liver disease severity and esophageal varices,8 and after propranolol administration.9 Consequently, blood ammonia levels could be higher in the group treated with beta-blockers, which matches with the higher incidence of encephalopathy in these patients. We conclude that data regarding blood NE and ammonia concentration would be useful for the interpretation of the observations of Sersté et al. Georgios N. Kalambokis M.D.*, Epameinondas V. Tsianos M.D., Ph.D.*, * First Division of Internal Medicine and Hepato-Gastroenterology Unit, Medical School of Ioannina, Ioannina, Greece.

102 Maintenance of Antibody Response to Pneumococcal Capsular Polysaccharide Vaccination in Adult Patients after Heart Transplantation

Purpose: The aim of this study was to evaluate the maintenance of antibody response to unconjugated pneumococcal capsular polysaccharide vaccine (PPV23) in adult heart recipients. Methods and Materials: 37 heart recipients (mean age 52 10) that were vaccinated with PPV23 at the time of inclusion in the waiting list, and 29 unvaccinated healthy controls (mean age 46 9 years) were analysed. Blood samples were taken pre-HT before vaccination (n 16) and after vaccination (n 17, mean time from vaccination: 143 days). Study points after HT: 7days (n 34), 1m (n 34), 3m (n 37), 6m (n 37), 12m (n 33) and 18m (n 22). Specific antibodies were measured using a commercial enzyme-linked immunosorbent assay technique (ELISA, Binding Site, Birmingham, UK; measuring range: 0.33-27 mg/dl). Results: In the pre-HT evaluation anti-PPS concentrations before vaccination were similar in heart recipients and controls (10 9 vs 10 8 mg/dl). After vaccination heart recipients disclosed significantly higher concentrations than controls: before HT (27 0.9, p 0.001,) and at 7days (20 8, p 0.001), 1m (19 9, p 0.001), 3m (18 9, p 0.001), 6m (16 9, p 0.005), and 12m (14 9, p 0.045) after-HT. There were no significant differences between both groups at 18m (12 9, p 0.21). Median fold increase of anti-PPS was 4.56 (pre-HT vs 7 days, interval: 0.54-17.42). There was a progressive decrease in anti-PPS which were significantly lower as compared with baseline post-vaccination values at all post-HT study points. During follow-up, 8 patients (20.5%) developed bacterial infectious complications. The frequency of heart recipients that maintained anti-PPS concentrations higher than 27 mg/dl during the first 3 months was 12.5% and 48% in patients with and without bacterial infections, respectively (p 0.07). Conclusions: Heart recipients maintained higher concentrations of antiPPS as compared with unvaccinated healthy controls up to 18 months after transplantation. Lower concentrations of anti-PPS mignt be associated with development of bacterial infections.

Pretransplant serum ferritin and C-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation

Although fluoroquinolones or other antibiotics are commonly used to prevent bacterial infections after hematopoietic cell transplantation (HCT), because of the growing presence of multidrug-resistant microorganisms, it is important to identify patients who are more likely to benefit from antibacterial prophylaxis. To evaluate risk factors for early bacterial infection after allogeneic HCT, we retrospectively analyzed clinical data for 112 consecutive adult patients with hematological malignancies who received transplants without any antibacterial prophylaxis. The cumulative incidence of bacterial infection at 30 days after transplantation was 16%. Among various pre-transplant factors, only high serum ferritin (>700 ng/mL, 47 patients) and high C-reactive protein (CRP) (>0.3 mg/dL, 28 patients) levels were significantly associated with the development of bacterial infection in a multivariate analysis (hazard ratio (95% confidence interval): ferritin, 4.00 (1.32-12.17); CRP, 3.64 (1.44-9.20)). In addition, septic shock and sepsis with organ failure were exclusively observed in patients who had high ferritin and/or high CRP levels. These results suggest that pretransplant serum ferritin and CRP levels can be useful markers for predicting the risk of early bacterial infection after allogeneic HCT. It may be prudent to limit antibacterial prophylaxis to patients with predefined risk factors to ensure the safety of HCT with the use of fewer antibiotics.

The use of FTIR microscopy for the evaluation of anti-bacterial agents activity

FTIR spectroscopy has been used by chemists as a powerful tool to characterize inorganic and organic compounds. In this study we examined the potential of FTIR microspectroscopy for early evaluation of the efficiency of anti-bacterial therapy. For this purpose, the effect of caffeic acid phenethyl ester ( CAPE) and ampicillin on the development of bacterial infection in cell culture was examined. CAPE is one of the most active components of propolis which is a natural honeybee product with a potent anti-bacterial activity. Our results show early (2 h post-treatment), unique and significant spectral indicators for successful treatment with CAPE although some of these biomarkers showed different trends in Gram (−) compared with Gram (+) bacteria. For instance, the intensity of bands at 682 and 1316 cm −1 decreases in all examined Gram (−) bacterial strains while significantly increases in all examined Gram (+) bacterial strains. On the other hand, both Gram (+) and Gram (−) bacteria treated with ampicillin did not show any spectral differences compared with the control untreated bacteria. It seems that FTIR spectroscopy can be used as an effective tool for an early evaluation of the efficiency of the anti-bacterial effect of CAPE and probably other used drugs.

A sad farewell and a new start

A sad farewell and a new start

Bacterial infections in cirrhosis

A bakteriális infekciók a májcirrhosis jól ismert szövődményei, jelentősen emelik a mortalitást. A májelégtelenség súlyossága és a gastrointestinalis vérzés fontos hajlamosító tényezők. A leggyakoribb fertőzések a spontán bakteriális peritonitis, a húgyúti és légúti fertőzések, valamint a sepsis. A kórokozók között azonos arányban fordulnak elő Gram-negatív és -pozitív baktériumok. Gastrointestinalis vérzés esetén (varix vagy nem varix eredetű) az ascites meglététől vagy hiányától függetlenül rövidtávú profilaktikus antibiotikus kezelés (per os norfloxacin vagy ciprofloxacin) javasolt (primer prevenció) . A kórházi kezelés ideje alatt gastrointestinalis vérzés hiányában is megfontolandó a norfloxacin adása alacsony ascites proteintartalom esetén. A spontán bakteriális peritonitis empirikus kezelésében iv. III. generációs cephalosporin adása javasolt, mely a tenyésztési lelet alapján célzott antibiotikus kezelésre váltható. A kezelés időtartama 5–8 nap. Jó alternatíva lehet az amoxicillin/klavulánsav kombináció, valamint korábban spontán bakteriális peritonitis profilaxisban nem részesülő betegek esetén valamely kinolonszármazék is. Az iv. megkezdett antibiotikus kezelés megfelelő klinikai javulás mellett 2 nap múlva per os kezelésre váltható. Veseelégtelenség társulása esetén kiegészítő albuminkezelés szükséges. Hosszú távú antibiotikum-profilaxis a spontán bakteriális peritonitis epizód lezajlását követően a gyakori kiújulás veszélye miatt minden betegnél indokolt (szekunder prevenció) . A „szelektív intestinalis dekontaminációra” leginkább a per os adott, elsősorban rosszul felszívódó fluorokinolonszármazék, a norfloxacin javasolt. A per os adott ciprofloxacin vagy méginkább a levofloxacin, ez utóbbi Gram-pozitívak ellen is hatékony, megfelelő alternatíva lehet. Trimetoprim/sulfamethoxazole adása csak abban az esetben jön szóba, ha a beteg nem kaphat kinolonszármazékot. A kezelést az ascites eltűnéséig; az ascites perzisztálása esetén a beteg élete végéig vagy a májtranszplantációig kell folytatni. A rezisztens törzsek kialakulásának veszélye miatt hosszútávú profilaxis spontán bakteriális peritonitisen még át nem esett asciteses cirrhosisos betegekben nem javasolt, akkor sem, ha az ascites terápia refrakter, vagy pedig fehérjetartalma alacsony.

Antibiotische Therapie und Prophylaxe bei Leberzirrhose und Infektion

Bacterial infections are a well-described complication in patients with cirrhosis of the liver. The development of an infection is associated with a significantly higher mortality. The most common infection in patients with liver cirrhosis is spontaneous bacterial peritonitis (SBP), an infection of ascites without an intraabdominal focus, followed by infections of the unrinary tract, pneumonia and sepsis. Early recognition of SBP results in an early antibiotic threrapy and thus improving survival. Another important role in the development of bacterial infections in cirrhosis is gastrointestinal hemorrhage. In patients with variceal hemorrhage, infection has been shown to be associated with failure to control bleeding and with early rebleeding. For these reasons, a prompt and appropriate antibiotic therapy is important and reduces mortalitiy in cirrhotic patients with bacterial infection.

Early enteral supply of fiber and Lactobacilli versus conventional nutrition: a controlled trial in patients with major abdominal surgery

OBJECTIVE: Early enteral nutrition with fiber-containing solutions plus Lactobacillus may reduce bacterial translocation and minimize the incidence of infections after surgery. METHODS: In a prospective, randomized trial in three groups ( n = 30/group) of patients after major abdominal surgery, we compared our previous regimen with parenteral nutrition or fiber-free enteral nutrition (group A) with enteral fiber-containing nutrition with living Lactobacillus (group B) and heat-killed Lactobacillus (group C). The main endpoint was the development of bacterial infection. Other analyzed parameters were the durations of antibiotic therapy and hospital stay, non-infectious complications, side effects of the nutrition, and onset of bowel movement. Routine parameters, nutritional parameters, and cellular immune status in the blood were measured preoperatively and on 1, 5, and 10 d postoperatively. RESULTS: The incidence of infections was significantly lower ( P = 0.01) in groups B and C with enteral nutrition containing fibers (10% each) than in group A (30%). Patients in group B received antibiotics for a significantly shorter time ( P = 0.04) than did the patients in groups A and C. The length of hospital stay and the incidence of non-infectious complications did not differ significantly. Fibers and lactobacilli were well tolerated. There were no general benefits of living Lactobacillus as opposed to heat-killed Lactobacillus in the entire study population, but benefits were observed in the patients with gastric and pancreas resections, although no statistical analysis was done due to their small numbers. CONCLUSIONS: Early enteral nutrition with fiber-containing solutions reduced the rate of postoperative infections in comparison with parenteral nutrition and fiber-free enteral formula. Addition of living Lactobacillus seemed to increase the benefits in patients with gastric and pancreatic resections.

Shear stress-induced apoptosis of adherent neutrophils: a mechanism for persistence of cardiovascular device infections.

The mechanisms underlying problematic cardiovascular device-associated infections are not understood. Because the outcome of the acute response to infection is largely dependent on the function of neutrophils, the persistence of these infections suggests that neutrophil function may be compromised because of cellular responses to shear stress. A rotating disk system was used to generate physiologically relevant shear stress levels (0-18 dynes/cm(2); 1 dyne = 10 microN) at the surface of a polyetherurethane urea film. We demonstrate that shear stress diminishes phagocytic ability in neutrophils adherent to a cardiovascular device material, and causes morphological and biochemical alterations that are consistent with those described for apoptosis. Complete neutrophil apoptosis occurred at shear stress levels above 6 dynes/cm(2) after only 1 h. Morphologically, these cells displayed irreversible cytoplasmic and nuclear condensation while maintaining intact membranes. Analysis of neutrophil area and filamentous actin content demonstrated concomitant decreases in both cell area and actin content with increasing levels of shear stress. Neutrophil phagocytosis of adherent bacteria decreased with increasing shear stress. Biochemical alterations included membrane phosphatidylserine exposure and DNA fragmentation, as evaluated by in situ annexin V and terminal deoxynucleotidyltransferase-mediated dUTP end labeling (TUNEL) assays, respectively. The potency of the shear-stress effect was emphasized by comparative inductive studies with adherent neutrophils under static conditions. The combination of tumor necrosis factor-alpha and cycloheximide was ineffective in inducing >21% apoptosis after 3 h. These findings suggest a mechanism through which shear stress plays an important role in the development of bacterial infections at the sites of cardiovascular device implantation.

Etiology of neutropenia in HIV-infected patients.

The causes of neutropenia in HIV-infected patients are described, as is the association of absolute neutrophil count (ANC) and the risk of bacterial infections. In patients with HIV infection, neutropenia can result from the disease or related malignancies, drug therapies, or opportunistic infections. HIV can cause neutropenia by directly or indirectly impairing hematopoiesis. Similarly, microorganisms that cause opportunistic infections, such as cytomegalovirus and Mycobacterium avium complex, can infiltrate the bone marrow and cause myelosuppression. Hematologic toxicities of drug therapy targeted against HIV and opportunistic infections, such as zidovudine, cidofovir, foscarnet, ganciclovir, and trimethoprim/sulfamethoxazole, can further reduce blood cell formation. Several retrospective studies are reviewed that examined the relationship between ANC and the development of bacterial infections in patients infected with HIV. Since neutropenia appears to be associated with increased risk of bacterial infections in HIV-infected patients, approaches to shorten or prevent neutropenia in these patients will likely provide substantial clinical benefit.

Neutropenia is associated with bacteremia in patients infected with the human immunodeficiency virus.

Neutropenia occurs in approximately 17% of symptomatic patients infected with HIV. Results of studies have failed to demonstrate a consistent relationship between HIV-related neutropenia and the subsequent development of bacterial infections. This was a case control study to determine if HIV-related neutropenia was associated with increased rates of bacteremia. The experimental group was comprised of 29 patients infected with HIV that had an absolute neutrophil count less than 1000 cells/mm3 and were paired with 29 control subjects infected with HIV that had been matched for age, sex, CD4 count, and month and year of entry. The frequency of bacteremia was 12.6 per 100 patient months among the experimental group compared to a frequency of 0.87 per 100 patient months among the control group (relative risk [RR] = 14.9, P = 0.0027). Other independent risks for the development of bacteremia included central venous catheters (RR = 3.9, P = 0.03), with a trend toward increased risk for bacteremia in those patients who were intravenous drug users (RR = 3.8, P = 0.11), or who had infiltrative bone marrow disease (RR = 3.1, P = 0.11). Multivariate analysis demonstrated that neutropenia (odds ratio [OR] = 22.6, P = 0.028) and the presence of a central venous catheter (OR = 8.5, P = 0.026) were significant risks for bacteremia. These data suggest that neutropenia is a significant risk for the development of bacteremia in patients infected with HIV.

Neutropenia and latrogenic Neutrophil Dysfunction in Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome

We appreciate the comments of Arnott and colleagues. We would like to point out that the controlled trial of Hardy et al 1 did show a statistically significant decrease not only in the log rank statistic comparing time with development of bacterial infection, but also in the frequency of infection (19 of 154 patients receiving trimethoprimsulfamethoxazole vs 38 of 156 patients receiving aerosol pentamidine; Fisher exact test, P=. 005). Therefore, we believe that it was appropriate to adjust for the use of trimethoprim-sulfamethoxazole in adult HIV-infected patients. In regard to use of pentamidine in our patients, there was no appreciable use of intravenous pentamidine during the relevant period in cases and controls. There was use of aerosol pentamidine for prophylaxis of P carinii pneumonia in some patients, but it is probably less likely that the inhaled form of the drug would be a confounding variable for bacterial pneumonia, particularly since