Management Of Bacterial Infections Research Articles

Optimization of on-chip bacterial culture conditions using the Box-Behnken design response surface methodology for faster drug susceptibility screening

Optimized culture conditions are essential for the investigation of biological processes. In this work, on-chip optimization of bacterial culture conditions by combining microfluidics with the Box-Behnken design response surface methodology is presented. With this methodology, the effects of several cultivation variables and their interactions were investigated enabling very fast drug susceptibility screening. The proposed measurement protocol for the determination of minimum inhibitory concentration (MIC) consist of three steps: i) single factor experiments to determine the effect of pH, nutrient concentration, and temperature on the bacterial culture; ii) analyses of the relationship between variables and the effect of the individual variables by means of the Box-Behnken design and response surface methodology (BBD-RSM) optimization; and iii) bacterial susceptibility screening of drugs and drug combinations. BBD-RSM is efficient to determine the optimal growth conditions of bacteria species with a strongly reduced amount of required experiments. On top of that, these experiments can in principle all be performed at the same time, yielding significant time-savings. The found optimized culture conditions of E. coli were applied to determine the MIC values of the drugs penicillin-streptomycin and baicalein, and combinations of those. MIC values were obtained within 8–14 h, including the 6–8 h required to determine the optimal growth parameters. The microfluidic BBD-RSM method results in a significant time reduction compared to the standard 2–4 days required to determine MIC values and is, therefore, a potential alternative in the management of bacterial infections.

Bacterial Infections in Neonates, Madagascar, 2012-2014.

Severe bacterial infections are a leading cause of death among neonates in low-income countries, which harbor several factors leading to emergence and spread of multidrug-resistant bacteria. Low-income countries should prioritize interventions to decrease neonatal infections; however, data are scarce, specifically from the community. To assess incidence, etiologies, and antimicrobial drug–resistance patterns of neonatal infections, during 2012–2014, we conducted a community-based prospective investigation of 981 newborns in rural and urban areas of Madagascar. The incidence of culture-confirmed severe neonatal infections was high: 17.7 cases/1,000 live births. Most (75%) occurred during the first week of life. The most common (81%) bacteria isolated were gram-negative. The incidence rate for multidrug-resistant neonatal infection was 7.7 cases/1,000 live births. In Madagascar, interventions to improve prevention, early diagnosis, and management of bacterial infections in neonates should be prioritized.

Management of bacterial infection in the liver transplant candidate.

Bacterial infection (BI) is a common cause of impairment of liver function in patients with cirrhosis, especially in the liver transplant candidates. These patients share an immunocompromised state and increased susceptibility to develop community and hospital-acquired infections. The changing epidemiology of BI, with an increase of multidrug resistant strains, especially in healthcare-associated settings, represents a critical issue both in the waiting list and in the post-operative management. This review focused on the role played by BI in patients awaiting liver transplantation, evaluating the risk of drop-out from the waiting list, the possibility to undergo liver transplantation after recovery from infection or during a controlled infection.

Infections complicating cirrhosis.

Patients with cirrhosis have a high risk of bacterial infections. Bacterial infections induce systemic inflammation that may lead to organ failure and acute-on-chronic liver failure (ACLF) resulting in a high risk of short term mortality. The early diagnosis and treatment of bacterial infections is essential to improve the patient's prognosis. However, in recent years, the spread of multidrug resistant (MDR) bacterial infections has reduced the efficacy of commonly used antibiotics such as third generation cephalosporins. In patients at high risk of MDR bacteria, such as those with nosocomial infections, the early administration of broad spectrum antibiotics has been shown to improve the prognosis. However, early de-escalation of antibiotics is recommended to reduce a further increase in antibiotic resistance. Strategies to prevent acute kidney injury and other organ failures should be implemented. Although prophylaxis of bacterial infections with antibiotics improves the prognosis in selected patients, their use should be limited to patients at high risk of developing infections. In this article, we review the pathogenesis and management of bacterial infections in patients with cirrhosis.

Antibiotic Resistance: The Danger for the Children

The introduction of antibacterial agents led to a revolution in the management of bacterial infections. Unfortunately, today we are facing an emerging and increasing resistance to antibiotics that become a threat to public health in Europe and globally. Infections in children are an important topic because children are highly susceptible to infections and hard to treat. That is why it is very important to lower resistance.

Continuous and Prolonged Intravenous β-Lactam Dosing: Implications for the Clinical Laboratory

Beta-lactam antibiotics serve as a cornerstone in the management of bacterial infections because of their wide spectrum of activity and low toxicity. Since resistance rates among bacteria are continuously on the rise and the pipeline for new antibiotics does not meet this trend, an optimization of current beta-lactam treatment is needed. This review provides an overview of optimization through use of prolonged- and continuous-infusion dosing strategies compared with more traditional intermittent infusions. Included is an overview of the scientific basis for using these nontraditional prolonged- and continuous-infusion-based regimens, with a focus on major areas in which the clinical laboratory can support the clinical use of these regimens.

Perspectives on Phytochemicals as Antibacterial Agents: An Outstanding Contribution to Modern Therapeutics.

Despite the considerable advancements in the development of antimicrobial agents, incidents of epidemics due to multi drug resistance in microorganisms have created a massive hazard to mankind. Due to increased resistance against conventional antibiotics, researchers and pharmaceutical industries are more concerned about novel therapeutic agents for the prevention of bacterial infections. Enormous wealth of traditional system of medicine gains importance in health therapies over again. With ancient credentials of potent medicinal plants, various herbal remedies came forward for the management of bacterial infections. The Ayurvedic approach facilitates the development of new therapeutic agents due to structural and functional diversity among phytochemicals. The abundance and diversity is responsible for the characterization of new lead structures from medicinal plants. Industrial interest has increased due to recent research advancements viz. synergistic and high-throughput screening approach for the evaluation of vast variety of phytochemicals. The review certainly emphasizes on the traditional medicines as alternatives to conventional chemotherapeutic drugs. The review briefly describes mode of action of various antibiotics and resistance mechanisms. This review focuses on the chemical diversity and various mechanisms of action of phytochemicals against bacterial pathogens.

In Vitro Antibacterial Activity of Selected Tanzania Medicinal Plants

Objective: To evaluate antibacterial activity from four selected medicinal plants namely Mystroxylon aethiopicum, Lonchocarpus capassa, Albizia anthelmentica and Myrica salicifolia used for management of bacterial infection in Tanzania. Methods: Minimum Inhibitory Concentration (MIC) of plants extracts against the tested bacterial species was determined by using 96 wells microdilution method. In this method, 50 μL of nutrient broth were loaded in each well followed by 50 μL of extract (100 mg/mL) to make a final volume of 100 μL. Subsequently 50 μL were transferred from first rows of each well to the second rows and the process was repeated down the columns to the last wells from which 50 μL were discarded. Thereafter, 50 μL of the selected bacterial suspension were added to each well thus making a final volume of 100 μL. The lowest concentration which showed no bacterial growth was considered as MIC. Results: It was revealed that L. capassa leaf ethyl acetate extract exhibited antibacterial activity against Salmonella kisarawe and Salmonella typhi with MIC values of 0.39 and 0.781 mg/mL respectively. Likewise, L. capassa root bark ethyl acetate extracts inhibited growth of S. typhi and E. coli with MIC values of 0.39 and 0.781 mg/mL respectively. The M. aethiopicum leaf and root bark chloroform extracts displayed antibacterial activity against S. kisarawe and S. typhi respectively with MIC value of 0.781 mg/mL. The M. salicifolia stem bark ethyl acetate exhibited antibacterial activity against P. aeruginosa with MIC value of 0.39 mg/mL whereas the methanolic stem and root bark of the same plant inhibited the growth of Proteus mirabilis and Klebsiella pneumoniae with MIC value of 0.781 mg/mL. Conclusion: It was concluded that M. aethiopicum, L. capassa, A. anthelmentica and M. salicifolia are potential source of antibacterial agents. Further studies to establish structures of antibacterial and evaluate active ingredients are recommended.

Urinary tract infections: diagnosis and management

Urinary tract infections are commonly seen in primary care. This review focuses on key points and recent guidelines on the diagnosis and management of bacterial infections.

Serum inhibitory and bactericidal titers in the clinical management of bacterial infections

Background The clinical management of bacterial infection computes factors related to bacteria (e.g., resistance profile [1]), antibiotics (e.g., activity spectrum, distribution volume, etc.), host characteristics (e.g., vascularization of the infected tissue, effectiveness of host defenses, etc.), as well as pharmacokinetic (PK) parameters [2]. The serum inhibitory (SIT) and bactericidal titers (SBT) are laboratory tests that simulate the interactions between antibiotics and bacteria in the human body milieu.

Chemical Composition and Antibacterial Activity of Essential Oil of Cosmos bipinnatus Cav. Leaves from South Africa.

The chemical composition of essential oils isolated from the leaves of Cosmos bipinnatus and its antibacterial activity were analyzed by GC-MS and microbroth dilution assay respectively. The essential oil extracted from this plant was predominantly composed of monoterpenes (69.62%) and sesquiterpenes (22.73%). The antibacterial assay showed that the oil had significant inhibitory effects against both Gram-negative and Gram-positive bacteria isolates. The MIC of Gram-positive strains ranged between 0.16 and 0.31 mg/mL while those of Gram-negative bacteria ranged between 0.31 and 0.63 mg/mL. The Gram-positive bacteria were more susceptible to the essential oil than the Gram-negative bacteria. Most of the major components of this oil in other plants have been reported for antimicrobial activities. The antibacterial activity can be attributed to effects of the combination of several components of the oil. The results indicate that the C. bipinnatus might be exploited as natural antibacterial agent and have application in the treatment of several infectious diseases caused by these bacteria. Since this species is endemic to the eastern Free State, the plant could be collected during its bloom and used efficiently in the management of bacterial infections in South Africa.

What’s New in the Management of Bacterial Infections in the Era of Multidrug-Resistant Bacteria?

Bacterial infection is an increasingly important diagnosis following successful organ transplantation in humans. This is notwithstanding the fact that opportunistic infections such as those of fungal and viral origin can occur frequently in this population. Infections due to multidrug resistant bacteria have been on the rise since the past decade and not surprisingly continue to challenge physicians. Recent studies show that rapidly increasing rates of infections in such population are due to methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and multidrug-resistant gram-negative bacilli. Furthermore, pan-drug-resistant infections are now on the rise, especially in gram-negative bacilli. Regrettably, our therapeutic options for these pathogens are currently extremely limited. Very recently, it has been shown that infections due to Clostridium difficile spp. have been the leading cause of antibiotic-associated diarrhea. It is a well-known fact that infections due to antimicrobial-resistant bacteria were associated with a greater likelihood of inappropriate antimicrobial therapy. Therefore, it is very clear that inappropriate antimicrobial therapy has an adverse effect on survival rate in patients with serious infections. This is especially true in immunocompromised hosts. Hence, in the light of the above, it is very essential that physicians who are treating immunocompromised patients should be aware of not only current epidemiological status of antimicrobial resistance but also proper clinical practice guidelines to be followed while diagnosing infections due to such antimicrobial agents. The objective of this review is, therefore, to provide a recent update of currently available antimicrobial therapeutic strategies for life-threatening infections due to antimicrobial-resistant pathogens.

A case of pneumonia and sepsis in cirrhosis as paradigm of the problems in the management of bacterial infections in cirrhosis and of the limitations of current knowledge

Bacterial infections are a major problem in the management of liver cirrhosis. They represent the first precipitating cause of death since patients with cirrhosis carry an increased risk of sepsis, sepsis-induced organ failure and death. Although the clinical presentation is often misleading, the presence of bacterial infection should always be actively searched and ruled out with certainty whenever a cirrhotic patient is admitted to the hospital with an acute clinical deterioration. Major changes in the epidemiology of bacterial infections have also occurred in the last decade making the choice of empirical antibiotic therapy a challenge. We report a paradigmatic case of a 54-year old man with hepatitis C-related cirrhosis admitted to the hospital for worsening of his ascites and onset of hepatic encephalopathy, an excellent example for the difficulties of management of sepsis in cirrhosis and the limits of current knowledge.

Preliminary Phytochemical Screening and Antibacterial Properties of Crude Stem Bark Extracts and Fractions of Parkia biglobosa (Jacq.)

A methanolic crude extract of Parkia biglobosa was prepared and later partitioned in succession with different solvents of increasing polarity ranging from n-hexane, chloroform and ethyl acetate to butanol. Phytochemical screening of the extract revealed the presence of alkaloids, tannins, saponins, flavonoids, steroids, glycoside and sugars. The inhibition zones exhibited by the extract against the tested bacteria ranged between 14 ± 0.00 mm (against Escherichia coli) and 28 ± 0.71 mm (against Pseudomonas aeruginosa). The MIC of the methanolic extract of P. biglobosa against isolates ranged between 0.63 mg/mL and 5 mg/mL, while the MIC values exhibited by the n-hexane and aqueous fractions ranged between 0.63 mg/mL and 10 mg/mL. Overall the extract and fractions of P. biglobosa used in this work were found to possess antimicrobial properties which compared favourably with those of streptomycin. These observations make this plant a potential source of bioactive compounds that can be used in management of bacterial infections. The use of this plant as herbal medicaments in African countries and the reports on the toxicity of the plant further show that the plant is non-toxic to humans.

A Simple Assay to Screen Antimicrobial Compounds Potentiating the Activity of Current Antibiotics

Antibiotic resistance continues to pose a significant problem in the management of bacterial infections, despite advances in antimicrobial chemotherapy and supportive care. Here, we suggest a simple, inexpensive, and easy-to-perform assay to screen antimicrobial compounds from natural products or synthetic chemical libraries for their potential to work in tandem with the available antibiotics against multiple drug-resistant bacteria. The aqueous extract of Juglans regia tree bark was tested against representative multiple drug-resistant bacteria in the aforementioned assay to determine whether it potentiates the activity of selected antibiotics. The aqueous extract of J. regia bark was added to Mueller-Hinton agar, followed by a lawn of multiple drug-resistant bacteria, Salmonella typhi or enteropathogenic E. coli. Next, filter paper discs impregnated with different classes of antibiotics were placed on the agar surface. Bacteria incubated with extract or antibiotics alone were used as controls. The results showed a significant increase (>30%) in the zone of inhibition around the aztreonam, cefuroxime, and ampicillin discs compared with bacteria incubated with the antibiotics/extract alone. In conclusion, our assay is able to detect either synergistic or additive action of J. regia extract against multiple drug-resistant bacteria when tested with a range of antibiotics.

Diagnosis and management of bacterial infections in decompensated cirrhosis

Bacterial infections are one of the most frequent complications in cirrhosis and result in high mortality rates. Patients with cirrhosis have altered and impaired immunity, which favours bacterial translocation. Episodes of infections are more frequent in patients with decompensated cirrhosis than those with compensated liver disease. The most common and life-threatening infection in cirrhosis is spontaneous bacterial peritonitis followed by urinary tract infections, pneumonia, endocarditis and skin and soft-tissue infections. Patients with decompensated cirrhosis have increased risk of developing sepsis, multiple organ failure and death. Risk factors associated with the development of infections are severe liver failure, variceal bleeding, low ascitic protein level and prior episodes of spontaneous bacterial peritonitis (SBP). The prognosis of these patients is closely related to a prompt and accurate diagnosis. An appropriate treatment decreases the mortality rates. Preventive strategies are the mainstay of the management of these patients. Empirical antibiotics should be started immediately following the diagnosis of SBP and the first-line antibiotic treatment is third-generation cephalosporins. However, the efficacy of currently recommended empirical antibiotic therapy is very low in nosocomial infections including SBP, compared to community-acquired episodes. This may be associated with the emergence of infections caused by Enterococcus faecium and extended-spectrum β-lactamase-producing Enterobacteriaceae, which are resistant to the first line antimicrobial agents used for treatment. The emergence of resistant bacteria, underlines the need to restrict the use of prophylactic antibiotics to patients with the greatest risk of infections. Nosocomial infections should be treated with wide spectrum antibiotics. Further studies of early diagnosis, prevention and treatment are needed to improve the outcomes in patients with decompensated cirrhosis.

Management of bacterial infections in cirrhosis

Bacterial infections are very frequent in advanced cirrhosis and become the first cause of death of these patients. Despite numerous experimental data and significant advances in the understanding of the pathogenesis of sepsis in cirrhosis, the outcome remains poor. Classical diagnostic parameters such as C-reactive protein and SIRS criteria have less diagnostic capacity in the cirrhotic population, often delaying the diagnosis and the management of bacterial infection. Prompt and appropriate empirical antibiotic treatment of infection and early resuscitation of patients with severe sepsis or septic shock are essential in determining patient's outcome. A strategy of careful restriction of prophylactic antibiotics to the high-risk populations could reduce the spread of multidrug resistant bacteria. This review is focused on the currently recommended diagnostic, therapeutic and prophylactic strategies for bacterial infections in the cirrhotic population.

English

Burn patients face an obviously high risk for infections due to the immunocompromising effects of their injury. This study aimed to detect and identify bacteria isolated from patients and hospital environment in the burn unit and determine their antibiogram pattern in response to commonly used antimicrobial agents; in order to give recommendations for management of bacterial infections and drug-resistance. Materials of this study were 100 samples of burn wounds and multiple swab samples of different hospital environments. One hundred and twelve isolates were analyzed, from which there was a single agent in the majority of cases (73.3%). Pseudomonas aeruginosawas the most common isolate (32.2%), followed by Enterobacter spp. (16.9%), coagulase-negative staphylococci (12.5%), Acinetobacter spp. (11.7%), Klebsiella spp. (8.9%), Staphylococcus aureus (7.2%), α-hemolytic streptococci (4.4%), and others (6.2%). The most commonly detected isolate from hospital environment was P. aeruginosa (35%) followed by Enterobacter spp., Klebsiella spp., coagulase-negative staphylococci. P. aeruginosa was the most resistant to third- and fourth-generation cephalosporins (100%), whereas other gram-negative bacteria were resistant to ciprofloxacin and cephalosporin (70 to 100%). Restriction in the abuse of antibiotics and establishment of an infection control unit will help lower the incidence of infection. Key words: Bacteriology, burn wounds, antibiogram, bacterial infections.

Prevention and Management of Bacterial Infections in Cirrhosis

Patients with cirrhosis of liver are at risk of developing serious bacterial infections due to altered immune defenses. Despite the widespread use of broad spectrum antibiotics, bacterial infection is responsible for up to a quarter of the deaths of patients with liver disease. Cirrhotic patients with gastrointestinal bleed have a considerably higher incidence of bacterial infections particularly spontaneous bacterial peritonitis. High index of suspicion is required to identify infections at an early stage in the absence of classical signs and symptoms. Energetic use of antibacterial treatment and supportive care has decreased the morbidity and mortality over the years; however, use of antibiotics has to be judicious, as their indiscriminate use can lead to antibiotic resistance with potentially disastrous consequences. Preventive strategies are still in evolution and involve use of antibiotic prophylaxis in patients with gastrointestinal bleeding and spontaneous bacterial infections and selective decontamination of the gut and oropharynx.

Improving Survival in Patients with Decompensated Cirrhosis

About 60% of patients with decompensated disease have oesophageal varices. One third of these patients will experience variceal bleed. Each bleeding episode compromises the decompensated state and is associated with a 20% to 30% mortality. Bleeding from ectopic varices is rare but is generally massive and life threatening. The first two articles, “Clinicopathological features and treatment of ectopic varices with portal hypertension” and “Application of endoscopy in improving survival of cirrhotic patients with acute variceal hemorrhage” discuss the management of variceal bleeding in cirrhotic patients. “Improved survival with the patients with variceal bleed” is a review article on how new treatment modalities have improved the outlook of patients with bleeding oesophageal varices. The hepatorenal syndrome (HRS) signifies advanced liver failure and is a bad prognostic factor in patients with decompensated cirrhosis. Management of this condition is discussed in “Management of renal failure and ascites in patients with cirrhosis”. One of the features of decompensated liver disease is the occurrence of recurrent or resistant ascites. Transjugular intrahepatic portosystemic shunt (TIPS) is an effective therapy for refractory ascites and HRS at the expense of hepatic encephalopathy and may offer an effective bridge to liver transplantation, by improving short and medium term survivals, as discussed in “Role of TIPS in improving survival of patients with decompensated liver disease”. Bacterial infection is responsible for up to a quarter of the deaths of patients with decompensated liver disease. “Prevention and management of bacterial infections in cirrhosis” discuss the high index of suspicion that is needed to prevent bacterial infections in patients with decompensated cirrhosis. These patients are immunologically compromised, and prophylactic antibiotics can prevent fatal septicemia and HRS in those with gastrointestinal bleeding. Current thoughts on how to deal with the neuropsychiatric complication of cirrhosis are discussed in “Management of hepatic encephalopathy”. Cardiomyopathy, hepatopulmonary syndrome, portopulmonary hypertension and right-sided hydrothorax complications that are often overlooked in patients with decompensated liver disease are discussed in “Management of cardiopulmonary complications of cirrhosis”. Decompensated liver cirrhosis has been traditionally considered as a prototype of hemorrhagic coagulopathy, and routinely performed coagulation profile is abnormal in the majority of these patients. In “Management of coagulopathy in patients with decompensated liver disease”, the authors discussed recent thoughts on coagulation in end-stage liver disease. The related article entitled “Determination of ADAMTS13 and its clinical significance for ADAMTS13 supplementation therapy to improve the survival of patients with decompensated liver cirrhosis” reviews the role of the deficiency of the metalloproteinase ADAMTS13 in end-stage liver cirrhosis in inducing platelet clumping or thrombi and how the resulting sinusoidal microcirculatory disturbances causes further liver damage and is closely related to further deterioration of liver function, hepatic encephalopathy, hepatorenal syndrome, and intractable ascites in advanced liver cirrhosis. Fresh frozen plasma (FFP) is a source of ADAMTS13. Liver cirrhosis is the common end stage of persistent liver injury. In the Asia Pacific region, these injuries commonly result from chronic hepatitis B and C infections as well as alcohol. The following two articles, “Treatment of hepatitis B in decompensated liver cirrhosis and treatment of decompensated alcoholic liver disease” address the management of hepatitis B and alcoholic liver disease in end stage liver disease. Pharmacotherapy in patients with decompensated liver disease is not without complications and side effects and might compromise the decompensated state. The article entitled “Prescribing medications in patients with decompensated liver cirrhosis” addresses the above conundrum. A common complication of liver cirrhosis is liver cancer, and treatment of this condition is challenging in patients with liver decompensation to say the least. The paper entitled “Screening for hepatocellular carcinoma” discusses early detection of liver cancer in these patients so that appropriate management can be arranged. Finally, liver transplantation for end-stage liver failure is discussed in “Indications and contraindications for liver transplantation”. Deepak Amarapurkar Rajiv Jalan Richard Guan Paul Kwo