The interferon system. A review of biological principles and clinical uses

Interferons are endogenous proteins produced by vertebrates in response to viral infections and is immunoregulatory agents. Three types of interferon are known today: IFN-alpha, IFN-beta und IFN-gamma which show different degree of relationship to each other in molecular structure and activity. Several interferons are produced in large amount by recombinant DNA technology. Their most important properties are their antiviral activity, their antiproliferative and immunoregulatory activities. Clinical trials showed that interferons can be used as therapeutic agents in viral infections and malignant diseases. Results of treatment in certain viral infections or virally induced tumors and some particular haematologic malignancies are very good. Many frequent forms of tumors still respond less or not at all to interferon treatment. Interferons have many different effects in vivo and can act synergistically with other agents. Further success in cancer therapy can therefore be expected from investigations on optimum dose schedule and effective combination regimes.     

Probiotics in the prevention and treatment of gastrointestinal infections

Probiotics have been studied in a variety of GI infections, and are an appealing concept given their favorable safety profiles. Several placebo-controlled trials indicated that lactobacilli have a suppressive effect on H pylori infection. Although some studies reported improvement in H pylori eradication, others failed to confirm this. Controlled trials support the use of Lactobacillus GG and S boulardii for the prevention of AAD, and have demonstrated the effectiveness of S boulardii as adjunctive therapy for RCDAD. Several placebo-controlled trials showed a reduction in the severity and duration of acute diarrhea in children with use of Lactobacillus GG. Studies of probiotics for the prevention of traveler's diarrhea yielded conflicting results, and their routine use cannot be recommended in this setting. Preliminary evidence suggests a potential role for reducing secondary pancreatic infections, although conclusive evidence is not available at this time. Additional clinical trials are indicated to define the role of probiotics further before wide-spread use can be recommended.     

A survey of the use of teicoplanin in patients with haematological malignancies and solid tumours

Summary A significant number of open and comparative studies have now addressed the use of teicoplanin in the treatment of documented or presumed infection in patients with haematological and non-haematological malignancy. Available evidence suggests that teicoplanin is an effective agent against such infections, with an excellent safety profile. The use of teicoplanin and vancomycin may be justified as part of the initial management of clinically infected right atrial catheters in patients with malignancy. The first-line use of glycopeptides may also be appropriate in units where streptococcal and methicillin resistant staphylococcal infections are prevalent. However, such a policy should be reviewed regularly. Except in the above situations, a delay in the introduction of either teicoplanin or vancomycin in cancer patients does not appear to produce any excess mortality, but there may be some additional morbidity in terms of fever and malaise. The introduction of glycopeptides as second-line agents is indicated for sensitive, microbiologically documented infections and for patients who have not responded to empirical, first-line therapy. Non-inpatient treatment with teicoplanin is an area of ongoing interest and may be justified on both humanitarian and pharmacoeconomic grounds. The use of glycopeptides in the prophylactic setting remains controversial and should be avoided while the emergence of resistance, particularly in enterococci, should be monitored closely.     

Treatment of respiratory and urinary tract infections in elderly inmates at a nursing home by selective antimicrobial agents based on the sensitivity of the isolated bacteria

OBJECTIVES: Elderly patients living in nursing homes can easily find themselves unable to carry out their daily activities, once they become ill, even with infectious diseases of a slight to mild degree, and rapid treatment is required to cure them of their malaise. However, treatment is often difficult due to the presence of drug-resistant bacteria. This study was designed to evaluate the efficacy of the selective use of antimicrobial agents based on a sensitivity test of isolated bacteria. METHODS: Possible pathogenic bacteria were isolated from cultures of pharyngeal swabs or urine obtained from patients with chronic febrile conditions or urinary tract infections, resistant to antimicrobial treatment. The efficacy of the treatment was evaluated based on release from febrile conditions and improvement of activities of daily living (ADL) accompanied by the disappearance of possible pathogenic bacteria following the use of selective antimicrobial agents. RESULTS: The outcome of 14 cases with sustaining febrile conditions and 3 cases with urinary tract infections was reviewed. Most of them showed a good response to treatment with remarkable improvement in ADL. In some cases, patients were switched from one antimicrobial agent to another each time new pathogenic bacteria were detected in the culture. A combination of rifampicin and sulfamethoxazole/trimethoprim (RFP/ST) was found to be the most convenient and effective treatment in patients with MRSA or drug-resistant Streptococcus pneumoniae. Levofloxacin (LVFX)-resistant Escherichia coli were detected together with MRSA in our 3 patients with urinary tract infections, corresponding to the frequent use of LVFX in our community. CONCLUSIONS: Identification of possible pathogenic bacteria and the use of proper antibiotic agents based on a sensitivity test are very effective in the treatment of elderly patients with chronic febrile conditions arising from the presence of drug-resistant bacteria. Careful use of fluoroquinolones is required in patients in whom MRSA is or had once been detected. This is beneficial not only for the elderly patients themselves but is also useful in preventing the spread of drug-resistant bacteria.     

Macrolides,ketolides and streptogramins

Macrolides, ketolides and streptogramins are three families of antibiotics with different chemical structures, sharing the same mechanism of action. All three bind to distinct bases of the peptidyl transferase center of ARNr 23S. Their antibacterial spectrum practically overlaps, but dissimilarities in affinity and/or number of binding sites determine differences in the intensity of their antibacterial effects (bacteriostatic or bactericidae) and in their activity against strains with acquired resistance mechanisms. These agents are active against the majority of gram-positive microorganisms and many intracellular microorganisms for growth. Over the last five years in our country, the percentage of macrolide-resistant pneumococci and S. pyogenes strains has increased substantially. Telithromycin (ketolide) and Synercid (streptogramin) have shown maintained activity against these strains. Macrolides, ketolides and streptogramins are metabolized in the liver through CYP 3A4 and they can partially block the activity of the enzyme, interfering with the metabolism of other drugs that use the same metabolic pathway. There is little elimination through the urine, with the exception of clarithromycin. High concentrations are reached in the cellular cytoplasm, but they do not diffuse to the CSF. These agents are included among class B drugs for use during pregnancy. Tolerance to macrolides and telithromycin is good and they have few associated adverse effects. The main clinical indication for these drugs is in empirical treatment of mild to moderate, community-acquired, upper and lower respiratory tract infections. Synercid is indicated in the treatment of infections due to methicillin-resistant staphylococci and glycopeptide-resistant enterococci.     

Isoniazid resistance among Bacillus Calmette Guerin strains: implications on bladder cancer immunotherapy related infections

Bacillus Calmette Guerin (BCG) immunotherapy is widely used for treatment of superficial bladder transitional cell carcinoma. Infectious complications while rare can be serious and severe disseminated infections as well as sepsis has been reported. There are no standard guidelines to direct therapy of these complications. Isoniazid is a commonly and widely used component of the various treatment regimens. Various strains of BCG are used for treatment of bladder cancer as well as vaccinations. These strains have evolved because of repeated subcultures in various laboratories in the world and have been shown to exhibit phenotypic differences in their immunogenicity as well as recently in susceptibility to various antimycobacterial agents. In this article, we review the resistance of BCG strains to various antimycobacterial agents. Some of these strains including the BCG Connaught strain, which is widely used in the United States, Canada and some other parts of the world for bladder cancer therapy exhibit intrinsic resistance to isoniazid. Although the clinical relevance of these differences is unclear, recent studies have questioned the role of isoniazid in treatment of infections after vaccination with these strains. Also, use of isoniazid in combination therapy for these infections may lead to the development of resistance to other antimycobacterial agents. We conclude that isoniazid may not be a suitable agent for empiric treatment of infections related to intravesical immunotherapy for bladder cancer with these strains and further studies are needed to clarify its role.     

When metformin is not enough: Pros and cons of SGLT2 and DPP‐4 inhibitors as a second line therapy

The newer oral therapies for type 2 diabetes mellitus, dipeptidyl peptidase‐4 (DPP‐4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors, have advantages over older agents. Dipeptidyl peptidase‐4 inhibitors are weight neutral and have few adverse effects. Sodium glucose cotransporter 2 inhibitors have additional benefits: weight loss, blood pressure reduction, cardiovascular risk reduction, and renoprotective effects. Sodium glucose cotransporter 2 inhibitors have increased risk of urogenital infections and possible risk of “euglycaemic” diabetic ketoacidosis. It is important to balance the benefits over the older‐oral therapies as these agents are more expensive; yet some analyses suggest that they are within the limits of what is considered cost‐effective in health care. We discuss the relative merits and drawbacks of these 2 classes and consider their roles in the treatment of type 2 diabetes mellitus. We suggest a number of patient profiles where early use of these agents could be used. We favour the use of SGLT2 inhibitors over DPP‐4 inhibitors as add on therapy to metformin when glycaemic targets have not been achieved given their similar glycaemic efficacy and the additional benefits of SGLT2 inhibitors. We particularly favour SGLT2 inhibitors in those where additional weight loss and blood pressure reductions are desired, and in patients with heart failure or cardiovascular disease. Care should be taken to warn patients about genital fungal infections and to avoid use in people with risk factors for SGLT2 associated ketoacidosis. We favour DPP‐4 inhibitors in those where side effects of other agents are of concern, the frail elderly population, and those with renal disease precluding SGTL2 inhibitor use.     

Infections in patients with chronic lymphocytic leukaemia: Mitigating risk in the era of targeted therapies

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia with infections a leading cause of morbidity and mortality. Recently there has been a paradigm shift from the use of chemo-immunotherapies to agents targeting specific B-lymphocyte pathways. These agents include ibrutinib, idelalisib and venetoclax. In this review, the risks and timing of infections associated with these agents are described, taking into account disease and treatment status. Treatment with ibrutinib as monotherapy or in combination with chemo-immunotherapies is not associated with additional risk for infection. In contrast, the use of idelalisib is associated with a 2-fold risk for severe infection and opportunistic infections. Venetoclax does not appear to be associated with additional infection risk. The evolving spectrum of pathogens responsible infections in CLL patients, especially those with relapsed and refractory disease are described, and prevention strategies (prophylaxis, monitoring and vaccination) are proposed.     

Is there a real risk of bacterial infection in patients receiving targeted and biological therapies?

Over the past decades, the advent of targeted and biological therapies has revolutionized the management of cancer and autoimmune, hematological and inflammatory conditions. Although a large amount of information is now available on the risk of opportunistic infections associated with some of these agents, the evidence regarding the susceptibility to bacterial infections is more limited. Biological agents have been shown to entail a variable risk of bacterial infections in pivotal randomized clinical trials and post-marketing studies. Recommendations on risk minimization strategies and therapeutic interventions are therefore scarce and often based on expert opinion, with only a few clear statements for some particular agents (i.e. meningococcal vaccination for patients receiving eculizumab). In the present review the available information regarding the incidence of and risk factors for bacterial infection associated with the use of different groups of biological agents is summarized according to their mechanisms of action, and recommendations based on this evidence are provided. Additional information coming from clinical research and real-world studies is required to address unmet questions in this emerging field.     

A current approach to diabetic foot infections

Foot infections are a common, complex, and serious problem in diabetic patients. Infections usually begin in foo ulcers, which are associated with neuropathy, vasculopathy, and various metabolic disturbances. These infections are potentially limb and sometimes life threatening. Etiologic agents are usually aerobic gram-positive cocci, but chronic or serious infections often contain gram-negative rods and anaerobes. Chronic infections can lead to contiguous bone infection. Diagnosing osteomyelitis may require imaging studies (especially magnetic resonance imaging) and occasionally bone biopsy. In addition to proper cleansing, debridement, and local wound care, diabetic foot infections require carefully selected antibiotic therapy. Serious infections necessitate hospitalization for initial parenteral broad-spectrum antibiotic therapy, but appropriately selected patients with mild infections can be treated as outpatients with oral (or even topical) agents. Initial antibiotic selection is usually empiric; modifications may be needed based on the results of properly obtained cultures and the clinical response. Therapy should be active against staphylococci and streptococci, with broader-spectrum agents indicated if polymicrobial infection is likely. Levels of most antibiotics, except fluoroquinolones, are often subtherapeutic in infected foot tissues. The duration of therapy ranges from a week (for mild soft tissue infections) to over 6 weeks (for osteomyelitis). No single antibiotic agent or combination has proven to be optimal. With appropriate local, surgical, and antimicrobial therapy, most diabetic foot infections can now be successfully treated.     

Role of oral fluoroquinolones in patients with respiratory diseases

The characteristics of recently developed oral fluoroquinolones include their broad spectrum involving gram-positive/gram-negative bacteria and atypical pathogens, potent antimicrobial activity against Pneumococcus, rapid tissue/sputum transfer, prolonged half-life, and reduction of their interaction with other agents. However, it has been reported that the common use of oral fluoroquinolones increases the number of fluoroquinolone-resistant bacterial strains. We review the appropriate use of these agents in patients with respiratory infections. In most cases, upper respiratory inflammation is a viral infection. Generally, antimicrobial agents are not necessary, and should not be administered. In Japan, a large number of antimicrobial agents, especially quinolones, are frequently prescribed to treat upper respiratory infection. This tendency must not be corrected. With respect to treatment for community-acquired pneumonia, it is controversial whether oral fluoroquinolones should be prescribed under various guidelines. In elderly patients and those with an underlying disease, oral fluoroquinolones may be a first-choice treatment at the outpatient clinic, because it is difficult to differentiate atypical pneumonia from bacterial pneumonia, and because the risk of drug-resistant Pneumococcus or gram-negative bacteria is high. With respect to treatment for hospital-acquired pneumonia, oral fluoroquinolones are recommended for patients with moderate or mild conditions without risk factors under the Guidelines established by the Japanese Respiratory Society. Bacteria causing acute infectious exacerbation in patients with chronic pulmonary diseases include gram-positive/gram-negative bacteria and anaerobic bacteria. Therefore, oral fluoroquinolones may be the most appropriate treatment for such patients. New oral fluoroquinolones show potent antimicrobial activity against tubercle bacillus, and may also be effective for infection with bacteria resistant to standard antitubercular agents. It may be controversial whether these agents should be indicated for atypical acid-fast bacterial infection.     

Cor pulmonale in chronic obstructive pulmonary disease. Circulatory pathophysiology and management

The development of pulmonary hypertension and right ventricular failure in COPD patients signals a poor prognosis. In hypoxic patients, long-term oxygen therapy prolongs life and appears to prevent or lessen the progression of pulmonary hypertension. However, oxygen therapy does not benefit and is not indicated for all COPD patients, and even in those patients who improve with oxygen, there remains a need to further improve survival. Therefore, there continues to be active investigations into pharmacologic agents that might reduce pulmonary hypertension or improve right ventricular function. Although many agents appear to have salutary acute effects, it has been more difficult to establish evidence for sustained hemodynamic benefits from chronic drug therapy. Furthermore, some effective agents may not provide additive benefit when combined with standard supplemental oxygen use, although the available data are limited. Clearly, further research is necessary to identify which COPD patients, if any, may benefit from either beta-agonists or vasodilators for the treatment or prevention of cor pulmonale at some time during the natural history of their disease.     

Antiviral therapy for respiratory tract infections

Viruses are important pathogens causing respiratory tract infections both in the community and health-care facility settings. They are extremely common causes of morbidity in the competent hosts and some are associated with significant mortality in the compromised individuals. With wider application of molecular techniques, novel viruses are being described and old viruses are found to have new significance in different epidemiological and clinical settings. Some of these emerging pathogens may have the potential to cause pandemics or global spread of a severe disease, as exemplified by severe acute respiratory syndrome and avian influenza. Antiviral therapy of viral respiratory infections is often unnecessary in the competent hosts because most of them are selflimiting and effective agents are not always available. In the immunocompromised individuals or for infections caused by highly pathogenic viruses, such as avian influenza viruses (AIV), antiviral treatment is highly desirable, despite the fact that many of the agents may not have undergone stringent clinical trials. In immunocompetent hosts, antiviral therapy can be stopped early because adaptive immune response can usually be mounted within 5-14 days. However, the duration of antiviral therapy in immunosuppressed hosts depends on clinical and radiological resolution, the degree and duration of immunosuppression, and therefore maintenance therapy is sometimes needed after the initial response. Immunotherapy and immunoprophylaxis appear to be promising directions for future research. Appropriate and targeted immunomodulation may play an important adjunctive role in some of these infections by limiting the extent of end-organ damage and multi-organ failure in some fulminant infections.     

Quinolones

Quinolones act by inhibiting enzymes (topoisomerases), which are indispensable to DNA synthesis. Their bactericidal activity is concentration-dependent. Their spectrum has become broader, especially since the introduction of a fluorine atom at position 6 (fluoroquinolones). They are used as the treatment of choice or as alternative therapy in a wide variety of infections, both in the hospital and non-hospital setting. Depending on the compound, they are used in urinary tract infections, sexually transmitted diseases, chronic osteomyelitis, respiratory tract infections, and severe systemic infections, among others. The upsurge and extent of quinolone resistance has limited the use of these agents in some cases and in future may determine their use in others. There are strategies to minimize the spread of resistance. Quinolones are safe and well tolerated. The most frequent adverse effects are gastrointestinal and those affecting the central nervous system.     

The use of itraconazole as prophylaxis against invasive fungal infection in blood and marrow transplant recipients

Invasive fungal infections play a key role in contributing to morbidity and mortality in patients undergoing treatment for haematological malignancies and related diseases. Risk factors for development of invasive fungal infections after blood or bone marrow transplantation include the use of broad‐spectrum antibiotics, steroids, mismatched or unrelated donor transplant, right atrial catheters, and prolonged or profound neutropenia. Previous attempts at use of oral itraconazole as antifungal prophylaxis in the setting of chemotherapy‐induced neutropenia were unsuccessful because of its poor absorption in capsule form. Itraconazole‐cyclodextrin is well absorbed even in the presence of chemotherapy‐induced neutropenia. Plasma levels of 250–500 ng/ml are required for prophylaxis. Studies to date show a favourable outcome in patients receiving itraconazole as prophylaxis against invasive fungal infections, although many studies looked at small numbers of patients and the incidence of invasive fungal infection in the control groups was low, prohibiting meaningful statistical evaluation. Fungi differ in their sensitivity to antifungal agents, and itraconazole is not the agent of choice in all patients. With the widespread use of antifungal prophylaxis, the possibility of resistance to antifungal agents and an increase in the number of invasive fungal infections caused by ubiquitous fungi previously considered nonpathogenic must be considered as potential problems.     

Central venous catheter (CVC)-related infections in neutropenic patients--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

Catheter-related infections cause considerable morbidity in hospitalised patients. The incidence does not seem to be higher in neutropenic patients than in non- neutropenic patients. Gram-positive bacteria (coagulase-negative staphylococci, Staphylococcus aureus) are the most frequently cultured pathogens, followed by Candida species. In contrast, Gram-negative bacteria play only a minor role in catheter-related infections. Positive blood cultures are the cornerstone in the diagnosis of catheter-related infections, while local signs of infection are only rarely present. However, a definite diagnosis generally requires the removal of the catheter and its microbiological examination. The role plate method with semiquantitative cultures (Maki) has been established as standard in most laboratories. Other standard procedures use quantitative techniques (Sherertz, Brun-Buisson) and are more sensitive. For therapy of catheter-related infections, antibiotics are administered according to the susceptibility of the cultured organism. Routine administration of gylcopepticed antibiotics is not indicated. Removal of the catheter has to be considered in any case of suspected catheter-related infection and is obligatory in Staphylococcus aureus and Candida infections. Tunnel or pocket infection of long-term catheters is always an indication for removal. In the future, the rate of catheter-related infections in neutropenic patients may be reduced by the use of catheters coated with antimicrobial agents.     

Staphylococcal infections in the intensive care unit

Staphylococcus aureus and coagulase-negative staphylococci are among the most common causes of nosocomial infections in the intensive care unit (ICU). The clinical presentation of staphylococcal device-related infections, pneumonias, or surgical wound infections is not unique. However, treatment of these infections is increasingly problematic because of the resistance of clinical isolates to a widening number of antimicrobial agents.The confluence of critically ill patients and the need for multiple invasive procedures, as well as the use of broad-spectrum antimicrobial agents in the ICU, set the stage for the emergence of these multidrug-resistant staphylococci. In the past 10 years, there has been a progressive increase in the overall resistance of staphylococci to antimicrobial agents. Conventional infection control measures, such as handwashing and isolation precautions, to prevent the spread of staphylococcal infections in the ICU setting remain of critical importance. New approaches, including the prophylactic use of topical antistaphylococcal agents to eliminate nasal colonization in high-risk ICU patients and the development of antistaphylococcal vaccines, are currently being investigated.     

The Prevention of Infections in Older Adults: Oral Health

The oral cavity is exposed to the external environment and from a very young age is colonized by infectious agents. Under certain circumstances including poor oral hygiene, dry mouth, trauma, and the use of antibiotics, oral infections can occur. They can result in damage to the oral cavity including teeth and their support structures. Oral infections can also lead to the extension of infection into surrounding tissues and to systemic infections. Chronic oral infection is a recognized risk factor for heart disease. Older adults are at high risk for oral infections and associated complications. Tooth loss, for which infection is the most significant cause, leads to cosmetic changes and a decreased ability to masticate certain foods that can lead to malnutrition. Chronic oral infections and the manipulation of teeth and supporting structures can lead to the hematogenous spread of infection including the infection of artificial joints and endocardial implants. Good oral hygiene, the use of fluoride, regular dental care, and the appropriate use of antibiotics can all reduce oral infections and their associated complications. J Am Geriatr Soc 68:411–416, 2020     

Nested case-control study on risk factors for opportunistic infections in patients with inflammatory bowel disease

BACKGROUND When opportunistic infections occur, patients with inflammatory bowel disease(IBD) commonly display a significantly increased rate of morbidity and mortality.With increasing use of immunosuppressive agents and biological agents,opportunistic infections are becoming a hot topic in the perspective of drug safety in IBD patients. Despite the well-established role of opportunistic infections in the prognosis of IBD patients, there are few epidemiological data investigating the incidence of opportunis-tic infections in IBD patients in China. Besides, the risk factors for opportunistic infection in Chinese IBD patients remain unclear.AIM To predict the incidence of opportunistic infections related to IBD in China, and explore the risk factors for opportunistic infections.METHODS A single-center, prospective study of IBD patients was conducted. The patients were followed for up to 12 mo to calculate the incidence of infections. For each infected IBD patient, two non-infected IBD patients were selected as controls. A conditional logistic regression analysis was used to assess associations between putative risk factors and opportunistic infections, which are represented as odds ratios(OR) and 95% confidence intervals(CIs).RESULTS Seventy(28.11%) out of 249 IBD patients developed opportunistic infections.Clostridium difficile infections and respiratory syncytial virus infections were found in 24 and 16 patients, respectively. In a univariate analysis, factors such as the severity of IBD, use of an immunosuppressant or immunosuppressants, high levels of fecal calprotectin, and C-reactive protein or erythrocyte sedimentation rate were individually related to a significantly increased risk of opportunistic infection. Multivariate analysis indicated that the use of any immunosuppressant yielded an OR of 3.247(95%CI: 1.128-9.341), whereas the use of any two immunosuppressants yielded an OR of 6.457(95%CI: 1.726-24.152) for opportunistic infection. Interestingly, when immunosuppressants were used in combination with infliximab(IFX) or 5-aminosalicylic acid, a significantly increased risk of opportunistic infection was also observed. The relative risk of opportunistic infection was greatest in IBD patients with severe disease activity(OR = 9.090; 95%CI: 1.532-53.941, relative to the remission stage). However, the use of IFX alone did not increase the risk of opportunistic infection.CONCLUSION Factors such as severe IBD, elevated levels of fecal calprotectin, and the use of immunosuppressive medications, especially when used in combination, are major risk factors for opportunistic infections in IBD patients. The use of IFX alone does not increase the risk of opportunistic infection.     

The role of newer antibiotics in gastroenterology.

The past decade has seen the introduction of a number of new potent antimicrobial agents, including broad-spectrum beta-lactam compounds such as the ureidopenicillins, third-generation cephalosporins, carbapenems, and monobactams; combinations of penicillins with inhibitors of beta-lactamase; and the quinolones. Most of these agents have excellent activity against enteric gram-negative rods and some are active against anaerobic organisms, the two bacterial groups most likely to be encountered in gastrointestinal infections. Despite the potency and wide spectrum of many of these new agents, there are currently relatively few clinical situations in which any of the newer antimicrobials are the first-line agents for therapy or prophylaxis of gastrointestinal diseases. Reluctance to use these agents as first-line therapy is based on concerns about the selection and spread of resistant organisms, superinfection syndromes, and the high cost of many of the newer agents. Specific clinical settings in which these agents may be given preference are as follows: 1. use of a third-generation cephalosporin (cefotaxime or ceftriaxone) in the treatment of spontaneous bacterial peritonitis. 2. use of broad-spectrum beta-lactam compounds to provide gram-negative coverage in patients who should not receive aminoglycosides 3. use of a third-generation cephalosporin (ceftriaxone) in the treatment of central nervous system relapses of Whipple's disease 4. use of quinolones for the empiric treatment of suspected bacterial diarrhea in patients sufficiently ill to require empiric initiation of antibiotics. 5. use of quinolones for the treatment of chronic carriers of Salmonella typhi 6. use of norfloxacin for prophylaxis against SBP. As further experience with these new antimicrobial agents is obtained and as more bacteria develop resistance to current first-line agents, there can be little doubt that these new antibiotics will play an increasing role in the prevention and treatment of gastrointestinal disease.