Development Of Antibiotic-resistant Organisms Research Articles

The Use of Long-term Antibiotics for Suppression of Bacterial Infections.

Suppressive antibiotic therapy is prescribed when a patient has an infection that is presumed to be incurable by a defined course of therapy or source control. The cohort receiving suppressive antibiotic therapy is typically highly comorbid and the infections often involve retained prosthetic material. In part due to a lack of clear guidelines regarding the use of suppressive antibiotics, and in part due to the complex nature of the infections in question, patients are often prescribed suppressive antibiotics for extremely long, if not indefinite, courses. The risks of prolonged antibiotic exposure in this context are not fully characterized, but they include adverse drug effects ranging from mild to severe, the development of antibiotic-resistant organisms, and perturbations of the gastrointestinal microbiome. In this narrative review we present the available evidence for the use of suppressive antibiotic therapy in 4 common indications, examine the gaps in the current literature, and explore the known and potential risks of this therapy. We also make suggestions for improving the quality of evidence in future studies, particularly by highlighting the need for a standardized term to describe the use of long courses of antibiotics to suppress hard-to-treat infections.

Patterns of inappropriate use of meropenem as antibacterial

Introduction: The development of antibiotic resistant organisms is related to inappropriate use of antibiotics, especially in developing countries where broad spectrum antibiotics can be purchased without prescription. Some of the common causes that contribute to the development of antimicrobial resistance are unnecessary use of antimicrobial drugs, inappropriate dose, inadequate duration of therapy. The aim of the study: The present study aiming to focus light on the inappropriate use of meropenem a lone, as it is one of the preserved last choices of antibiotics and is under restricted regulations for description and dispensing by ministry of health in Iraq. Materials and methods: This study was carried out in Tertiary –care hospital. Hundred and thirty patients received meropenem had included in this study. The meropenem administration was followed up regarding dose, frequency, duration, indication. The bacteria were isolated and identified by standard conventional methods in addition to Api20E systems. Antibiotic sensitivity testing carried out by Kirby-Bauer disc diffusion method. The result: Collectively 54% of the patients included in this study recieved meropenem inappropriately. The antibiotics sensitivity test by the hospital was inadequate. The most common bacteria isolated from the study were gram negative bacteria (72.7%). E.coli was the most predominant isolated bacteria (32%). Conclusion: The abuse of antibiotics is very common especially because antibiotic sensitivity test is almost neglected in Iraq. Fundamental changes are required to solve this problem. For the future of the next generations let us start a new policy in prescribing and dispensing antibiotics in Iraq

Surveillance and Prevention of Surgical Site Infections in Breast Oncologic Surgery with Immediate Reconstruction.

Surgical site infection (SSI) after immediate breast reconstruction is much more common than would be expected after a clean surgical procedure. Although the SSI rates reported in individual studies are quite variable, there are no obvious explanations for the variation in infection rates between institutions. The microbiology of these SSIs is unusual, with higher proportions of infections caused by atypical Myobacterium species and Gram-negative bacilli than would be expected for this anatomic site. In an effort to prevent SSIs, many surgeons use a variety of different practices including irrigation and soaking of implants with antibiotic solutions and prolonged duration of prophylactic antibiotics, although the literature to support these practices is very sparse. In particular, prolonged use of antibiotics post-discharge is concerning due to the potential for harm, including increased risk of Clostridium difficile infection, development of antibiotic resistant organisms, and drug-related allergic reactions. With higher rates of mastectomy and breast implant reconstruction in women with early-stage breast cancer, including greater utilization of reconstruction in higher-risk individuals, the number of women suffering from infection after oncologic reconstruction will likely continue to increase. It is imperative that more research be done to identify modifiable factors associated with increased risk of infection. It is also essential that larger studies with rigorous study designs be performed to identify optimal strategies to decrease the risk of SSI in this vulnerable population.

Antibiotic resistance genes as an emerging environmental contaminant

Emerging contaminants, including pharmaceutical and personal care products, are receiving considerable attention owing to their potential to negatively impact the environment and to pose risks to human health. The widespread use of antibiotics and their fate and transport in the environment pose further risks with respect to public health and the development of antibiotic resistant organisms (AROs). While the occurrence of AROs is important, there is increasing interest in antibiotic resistance genes (ARGs). An urgent need exists to improve our understanding of the mechanisms associated with the spread and development of ARGs in both clinical and veterinary settings, the human body (gastrointestinal tract and microbiome) as well as in engineered (wastewater treatment plants) and natural (soil, sediments and water) environments. This review focuses on ARGs as an emerging environmental contaminant. The factors and mechanisms involved in ARG dissemination in a variety of environments are explored in detail. The unique challenges of ARGs with respect to policy-making and environmental monitoring are identified, and recommendations regarding how these challenges might be addressed are provided.

CORR Insights(®): Is Vancomycin-only Prophylaxis for Patients With Penicillin Allergy Associated With Increased Risk of Infection After Arthroplasty?

Where Are We Now? Deep prosthetic joint infections (PJI) following total joint arthroplasty (TJA) can be catastrophic. Timely administration of intravenous antibiotics prior to surgical incision is one of the most effective strategies to prevention of postoperative infections [6]. Currently, first- or second-generation cephalosporins are recommended for prophylaxis prior to routine THA and TKA [1]. However, in recent years, changes in patient demographics and increasing prevalence of resistant organisms in patients undergoing lower-extremity arthroplasty have raised the question of whether current recommendations are adequate. Combination therapies including the routine addition of vancomycin to the prophylactic antimicrobial regimen have shown only comparable efficacy to monotherapy in some studies, while increasing the risk of acute kidney injury in others [3, 8]. Furthermore, decolonization protocols have also been shown to be variable in terms of compliance and efficacy [10]. Therefore, the question remains: What is the correct approach to antibiotic prophylaxis prior to hip or knee replacement? In this article, Tan et al. present an interesting study on the use of vancomycin alone for prophylaxis in patients with penicillin allergies undergoing TJA. The authors found that administration of vancomycin alone did not increase the rate of deep surgical site infections, but decreased the risk for infections with Gram-positive organisms and antibiotic resistant organisms. Where Do We Need To Go? This work adds valuable information, but a number of questions remain. It would be important to validate these findings in other centers, and in prospective studies that permit tighter standardization of clinical practices. Of course, the endpoint we are most interested in—deep infection—requires much larger (and almost certainly multicenter) studies. The allure of widespread utilization of vancomycin as an effective agent to prevent infections with resistant organisms must be tempered by the potential risks, including renal toxicity, ototoxicity, and antimicrobial resistance. However, this is a common clinical scenario that not only affects arthroplasty surgeons, but all orthopaedic surgeons. Even though cross-reactivity and true anaphylaxis resulting from cephalosporin administration is only approximately 10% [2], most surgeons opt for antibiotic alternatives rather than “test-dosing” the patient under anesthesia to determine the presence or absence of true allergy. Vancomycin and clindamycin are commonly used alternatives in these situations, but concerns remain with regards to the efficacy of clindamycin and coverage of vancomycin as stand-alone agents [9]. Other studies have shown an increased risk of infections when only vancomycin is administered for routine prophylaxis [7]. Consequently, larger, prospective studies taking into account host factors, local antibiograms, and clinical practices such as decolonization protocols will be needed to definitively define the indications and efficacy for various antibiotic prophylactic protocols surrounding TJA. How Do We Get There? Many factors contribute to the risk of surgical site infections, and so to study the impact of antibiotics on infection properly, a multidisciplinary approach is called for. First, standardization of definitions and clinical practices will allow us to collaborate to find an answer to this problem without introducing confounding variables and bias. Today, there are established criteria for the work-up and diagnosis for infected TJA as well as clinical practice guidelines for the management of the infected TJA [5]. Second, a creation and contribution of surgical site infection and PJI data to various local and national registries will allow surveillance at a population level and the development of protocols based on specific antibiograms. Finally, and perhaps most challenging, is the need to define the “optimized” candidate for joint arthroplasty. Conditions such as diabetes, chronic kidney disease, obesity, and malnutrition have been shown to place patients at increased risk for development of infections postoperatively [4]. We need more studies that specifically ascertain at what point we should consider those sorts of conditions “well enough” managed that it is clinically reasonable to proceed with elective arthroplasty. Because of the increased risk, those studies also should help us to determine whether these higher-risk patients should be treated with different antibiotic approaches than low-risk patients? Identifying the correct antibiotic prophylaxis protocols can have profound and wide-reaching impact. The cost to prevent a single patient's infection must be counterbalanced against the risks in that patient of adverse effects, but also against societal costs, such as the development of antibiotic-resistant organisms. Orthopaedic surgeons, will be at the forefront of this dilemma and must play a part in practicing good, evidence-based, antibiotic stewardship.

What are the patterns of prophylactic postoperative oral antibiotic use after foot and ankle surgery?

The CDC estimates 23% of healthcare-associated infections to be surgical site infections, with alarming prevalence of antibiotic-resistant organisms. While there is consensus regarding preoperative prophylaxis, orthopaedic surgeons' use of prophylactic postoperative oral antibiotics is less defined. We investigated surgeons' use of prophylactic postoperative oral antibiotics after elective outpatient foot or ankle procedures, identifying (1) frequency of use, (2) regimen preferences, (3) personal indications, and (4) associated experience and demographics. Using a cross-sectional survey design, a questionnaire was emailed to all active and candidate members of the American Orthopaedic Foot and Ankle Society. Supplementary questions captured demographic information. We invited 1136 members to participate; 22 addresses produced delivery failure messages, leaving 1114 members as potential participants. After nonresponses and exclusions, 312 (28%) responses were analyzed. Statistical analysis used Pearson's chi-square test, Fisher's exact test, and multivariate regression. The majority (75%) of respondents reported use of prophylactic postoperative oral antibiotics. Most users (69%) prescribed to fewer than 25% of patients, although 16% prescribed for all elective cases. The most frequent regimen was cephalexin 500 mg four times a day (63%) and the most common duration was 5 to 7 days (50%). Surgeons' most common indications were previous infection (71%), medical comorbidities (65%), and previous wound-healing difficulties (56%). Those who do and do not prescribe prophylactic postoperative oral antibiotics showed no difference in surgical site infection rate or any demographic category. Surgeons' reported use of prophylactic postoperative oral antibiotics after elective foot or ankle surgery was common, without demographic association. Commonalities were identified in antibiotic regimen and personal indications for this practice. Comparative clinical studies are warranted to elucidate the efficacy of prophylactic postoperative oral antibiotics and establish evidence-based guidelines for their use.

569: Effects of Piperacillin -Tazobactam Perioperative Pneumonia Prophylaxis on Outcomes in the First 30 days Post Lung Transplantation

The development of antibiotic resistant organisms is especially concerning in lung transplantation. We recently broadened our perioperative prophylaxis to more aggressively prophylax for peri-operative pneumonia. We chose Piperacillin-Tazobactam (P-T) based on known nosocomial bacterial flora. We evaluated the impact of P-T based strategy on patient exposure to antibiotics, ICU length of stay (LOS), and incidence of resistant (R) organisms to P-T within 30 days post-op.

Burns, biofilm and a new appraisal of burn wound sepsis

Purpose Following a burn, the wound may become colonized and septic complications may ensue. Many organisms, commonly isolated from burn wounds produce biofilms, which are defined as a collection of organisms on a surface surrounded by a matrix. Biofilms are associated with development of antibiotic resistant organisms and are refractory to the immune system. The presence of biofilm in the burn wound has not been documented. Methods A study was undertaken using light and electron microscopy to determine the presence of biofilm in the burn wound. Specific stains were used to detect the presence of micro-organisms and associated carbohydrate, a major constituent of the biofilm matrix. A concurrent microbiological study of the burn wound was also carried out. Results Biofilm was detected in ulcerated areas of the burn wound. Bacterial wound invasion with mixed organisms was also commonly detected. Conclusions The finding of biofilm in the burn wound has significance in our understanding of burn wound sepsis and supports the evidence for early excision and closure of the burn wound. Due to the recalcitrant nature of biofilm associated sepsis and the difficulty in disrupting biofilm it has implications for the future development of wound care dressings.

The Antibiotic Resistance Problem Revisited

Mr. C was a wealthy 49-year-old Argentine businessman who was generally too busy to see a physician when he felt ill, preferring to treat himself with antibiotics and other drugs he purchased at his local pharmacy. He experienced intermittent periods of coughing, fever, and fatigue for several weeks, finally consulting his physician who found small bleeds under Mr. C's skin, and decided to run blood tests. The diagnosis was leukemia, and Mr. C sought treatment in Boston. The diagnosis was confirmed, and appropriate treatment for his leukemia and a bacterial infection, the source of the high fever, was begun. After 10 days of chemotherapy for the leukemia, no abnormal cells were seen in his blood. A bone marrow test on Day 17 showed that he had responded to the leukemia treatment and was on his way to remission. However, the Escherichia coli infection responsible for his high fever was proving intractable. Lab results revealed that it was resistant to eight different antibiotics, including the newer cephalosporins. On Day 20 Mr. C lost consciousness due to an intracranial bleed, and on Day 22 he died. Autopsy results showed no trace of leukemia, but multiple sites of E. coli infection. His intestinal tract had become an incubator for the development of antibiotic resistant organisms, including the E. coli which led to his death (Levy, 2002). Mr. C obviously had no difficulty in simply walking in to a pharmacy and purchasing over-the-counter antibiotics, and most likely received little guidance as to antibiotic selection and course of treatment. In his case, this practice undoubtedly was a significant factor in his death. Over-the-counter (OTC) availability of antibiotics is a problem in nations other than Argentina. Amabile-Cuevas (2003) estimates that approximately 30% of antibiotic purchases in Mexico City drugstores are OTC, and in the U.S. soldiers often buy antibiotics intended for treating aquarium fish to save money. E. coli is by no means the only microbe associated with antibiotic resistance. The Centers for Disease Control and Prevention list several other diseases and pathogens associated with this public health problem (see Table 1). The problem remains a serious public health concern responsible for two million nosocomial (hospital-acquired) infections/ year in the U.S. at an excessive treatment cost of six billion dollars/year (Vecchione & Sipkoff, 2007) and resulting in 100,000 deaths/year. Compared with hospital-acquired infections, the numbers of community-acquired infections from antibiotic resistant organisms are much more difficult to estimate. While Mr. C's story illustrates the serious nature of the antibiotic resistance problem, similar tales of the significance of infection with antibiotic resistant organisms abound in the literature. * Shane Matthews, former Chicago Bears starting quarterback, underwent surgery for a hernia repair in 1999. He acquired a methicillin-resistant Staphylococcus aureus (MRSA) infection while in the hospital, spending three months in the hospital fighting the infection. He survived, but lost 30 pounds and much of his strength in the battle. It took him almost two years to regain his strength (Levy & Fischetti, 2004). * Salmonella typhimurium DT104, has been responsible for three major human outbreaks in the U.S. since 1996, all of animal origin. This organism often carries multiple resistance determinants, evidenced by the Food and Drug Administration's isolation of one strain carrying resistance to 12 different antibiotics (Walters, 2003). * More than two billion of the world's six billion population have latent tuberculosis, including 10-15 million Americans. Eight million active cases are diagnosed globally each year. In the tuberculosis epidemic in New York City from 1979-92, over one-third of the cases were multi-drug resistant (MDR-TB). The city's response included local screening programs, Directly Observed Therapy-Short Term (DOTS) clinics, improved health care in city jails, plus quarantine for some patients (only 11 % completed therapy voluntarily) at a total cost of over a billion dollars (Markel, 2004). …

A Performance Improvement Monitor: Criteria for Antibiotic Therapy

ISSUE: Despite CDC and state health department campaigns, inappropriate use of antibiotics continues to be an issue in health care facilities. Excessive and unneccesary antibiotic usage contributes to the development of antibiotic resistant organisms and is often responsible for adverse side effects. There is often inconsistency in adhering to consistent, established criteria for initiating antibiotic therapy(ABT). PROJECT: A Performance Improvement Monitor was initated at our facility in January 2005 with the primary indicator, “Appropriate Use of Antibiotics.” The criteria selected for monitoring were: A.fever above 100°F. for 24 hours B.positive culture (along with abnormal urinalysis if UTI) C.abnormal CXR with respiratory signs and symptoms D.WBC over 11.0 with left shift E.other criteria (addressed in data analysis: example-prophylaxis for traumatic laceration; cellulitis) An Excel data collection tool was developed. Study parameters were presented at a Medical Staff Meeting prior to the initiation of the project. METHODOLOGY: Patients on one clinical unit were reviewed. A weekly antibiotic listing was received from pharmacy. IC Director reviewed charts of all pts. on antibiotics. RESULTS: Once physicians became aware of the existence and parameters of this monitor, there was an observable change in antibiotic prescribing patterns. Physicians on this unit became more consistent in documenting clinical rationale for antibiotic use. Over the time frame of this project, there has been an improvement in prescribing practices. Indicator compliance - 1st quarter-72% (N = 62) 2nd quarter-93% (N = 60) 3r quarter-92% (N = 55) 4th quarter-90% (N = 59) Data is reported quarterly to individual physicians so they may review their prescribing patterns. This report includes patient specific information relevant to each antibiotic ordered, along with area of noncompliance. LESSONS LEARNED: This monitor has been instrumental in improving the antibiotic prescribing practices on this unit at our facility. As a result of the study, support staff have been educated on ABT and proper specimen collection. Quarterly compliance rates for the unit are shared with nurses at staff meetings. As a result, the nursing staff became more aware of the issue of antibiotic overuse, as well as proper specimen collection protocols. This was a challenging project to implement as there were no data collection parameters or tools available in the literature. ISSUE: Despite CDC and state health department campaigns, inappropriate use of antibiotics continues to be an issue in health care facilities. Excessive and unneccesary antibiotic usage contributes to the development of antibiotic resistant organisms and is often responsible for adverse side effects. There is often inconsistency in adhering to consistent, established criteria for initiating antibiotic therapy(ABT). PROJECT: A Performance Improvement Monitor was initated at our facility in January 2005 with the primary indicator, “Appropriate Use of Antibiotics.” The criteria selected for monitoring were: A.fever above 100°F. for 24 hours B.positive culture (along with abnormal urinalysis if UTI) C.abnormal CXR with respiratory signs and symptoms D.WBC over 11.0 with left shift E.other criteria (addressed in data analysis: example-prophylaxis for traumatic laceration; cellulitis) An Excel data collection tool was developed. Study parameters were presented at a Medical Staff Meeting prior to the initiation of the project. METHODOLOGY: Patients on one clinical unit were reviewed. A weekly antibiotic listing was received from pharmacy. IC Director reviewed charts of all pts. on antibiotics. RESULTS: Once physicians became aware of the existence and parameters of this monitor, there was an observable change in antibiotic prescribing patterns. Physicians on this unit became more consistent in documenting clinical rationale for antibiotic use. Over the time frame of this project, there has been an improvement in prescribing practices. Indicator compliance - 1st quarter-72% (N = 62) 2nd quarter-93% (N = 60) 3r quarter-92% (N = 55) 4th quarter-90% (N = 59) Data is reported quarterly to individual physicians so they may review their prescribing patterns. This report includes patient specific information relevant to each antibiotic ordered, along with area of noncompliance. LESSONS LEARNED: This monitor has been instrumental in improving the antibiotic prescribing practices on this unit at our facility. As a result of the study, support staff have been educated on ABT and proper specimen collection. Quarterly compliance rates for the unit are shared with nurses at staff meetings. As a result, the nursing staff became more aware of the issue of antibiotic overuse, as well as proper specimen collection protocols. This was a challenging project to implement as there were no data collection parameters or tools available in the literature.

Spontaneous bacterial peritonitis: a historical perspective: Kerr DNS, Pearson DT, Read AE. Infection of ascitic fluid in patients with hepatic cirrhosis [Gut 1963; 4: 394–398]; Conn HO. Spontaneous peritonitis and bacteremia in Laennec's cirrhosis caused by enteric organisms. A relatively common but rarely recognized syndrome [Ann Intern Med 1964; 60: 568–580

Spontaneous bacterial peritonitis: a historical perspective: Kerr DNS, Pearson DT, Read AE. Infection of ascitic fluid in patients with hepatic cirrhosis [Gut 1963; 4: 394–398]; Conn HO. Spontaneous peritonitis and bacteremia in Laennec's cirrhosis caused by enteric organisms. A relatively common but rarely recognized syndrome [Ann Intern Med 1964; 60: 568–580

The development of antibiotic resistant organisms with the use of ototopical medications

Objective There is growing concern over the use of systemic antibiotics and the development of bacterial resistance. The question remains as to whether ototopical medications may also promote antibiotic-resistant organisms, either on a local level (in the ear) or in other areas of the aerodigestive tract. We performed an evidence-based review to answer the following clinical question, “Do antibiotic ototopical medications induce antibiotic resistant organisms?” Study design We performed a MEDLINE search of the published literature from 1966 to the present. We used appropriate search terms such as “ototopical antibiotics,” “ototopical drops,” “antibiotic resistance,” “topical antibiotics and otitis externa,” “otitis externa and treatment,” “otitis externa and antibiotic drops,” “otitis externa and ototopical drops,” “otitis media,” “otitis media and treatment,” “otitis media and antibiotic drops,” “chronic suppurative otitis media,” “chronic suppurative otitis media and treatment,” “chronic suppurative otitis media and antibiotic drops,” “ otitis externa and resistant organisms,” “otitis media and resistant organisms,” “chronic suppurative otitis media and resistant organisms,” “ophthalmic antibiotic drops,” “draining ear,” “P.E. tube otorrhea,” “pressure equalizing tube otorrhea,” “pressure equalizing tube otorrhea and treatment,” and “pressure equalizing tube otorrhea and ototopical therapy” to identify pertinent articles. These articles were reviewed and graded according to the evidence quality. Results After an initial screening of over 2,500 articles, 38 articles were analyzed further; of these, 11 were determined to warrant extensive review. Eight articles evaluated chronic suppurative otitis media; 2, otitis externa; and 1, post–tympanostomy tube otorrhea, whereas 3 others studied systemic absorption. Of the 8 chronic suppurative otitis media studies, there were thought to be 5 grade 2B studies, 1 grade 1B study, and 1 grade 2C study. These studies did not demonstrate a propensity for the development of resistant organisms. No study answered the question as to whether resistance to systemic antibiotics might occur in otitis externa. Conclusions Overall grade B evidence seems to indicate that no significant antibiotic resistance develops from the use of ototopical antibiotic treatment.

Outpatient treatment suite: a safe and cost-effective venue to perform myringotomy and tubes placement in children

Context: Otitis media (OM) is the most common reason that a child undergoes a general anesthetic, with the total costs of treating this disease exceeding five billion dollars annually. Concerns regarding the development of antibiotic-resistant organisms in response to medical treatment for OM have fueled the demand for surgical intervention. However, reimbursements are decreasing. Non-traditional settings for children requiring bilateral myringotomy and tube (BMT) placement for ear disease have the potential to offer the same degree of patient safety and improved efficiency but at lower cost. Objective: To develop a non-traditional setting for BMT surgery that is safe, cost effective, and well received by patients, families and staff. Design: Prospective design of an outpatient treatment suite (OTS) for BMT placement; prospective evaluation of safety and family satisfaction; analysis of costs. Setting: A 778 bed US urban area level one trauma center and teaching hospital, with a 2160 ft 2 electro-convulsive therapy suite that was underutilized and non-revenue generating on Tuesdays and Thursdays. Participants: A design task force of health care providers, administrators and operations personnel; 794 healthy children between the ages of 6 months to 16 years requiring BMT surgery; 100 families of patients. Main outcome measures: Financial comparison was made between the traditional operating room (OR) setting, the outpatient surgery center (SC) and the OTS comparing overhead and indirect costs to run each site. A prospective survey was conducted of 100 consecutive patients undergoing surgery between November 2000 and June 2001. The survey was conducted at the 2 weeks postoperative check and was composed of 18 questions divided into five sections, with a 5-point rating scheme, with one being very poor, and five being very good. Results: Designing a new treatment venue was successful because of teamwork and a willingness to think creatively. The OTS was found to be far more cost-effective than both the main OR and SC for BMTs. The contribution to margin for the SC was US$ 280 per case and for the main OR was US$ 2130 per case. By operating on 794 patients in OTS, the hospital was able to generate additional contribution to margin of US$ 197,100 when compared to the cost of performing these cases in the SC and US$ 1,499,500 when compared to performing all cases in the main OR. No adverse consequences were noted. Patient/Family satisfaction was also rated very high, with an overall rating of 4.85 and markedly reduced time in hospital. Conclusion: Operating rooms (ORs) today are busier than in years past, but revenues barely meet or in some cases fall below expenses due to insurers’ decreased reimbursement. This innovative approach to BMT placement has been shown to be safe and results in excellent family satisfaction, with a substantial contribution to margin. As over one million BMT cases are performed annually in the US, adoption of this approach nationally has the potential to markedly reduce the treatment costs of this common disease.

Passive immunity against human pathogens using bovine antibodies.

The control and treatment of infectious diseases is increasingly complicated by the development of antibiotic-resistant organisms, the emergence and rapid dissemination of new pathogens, and the growing incidence of opportunistic infections. Identification and commercialization of new anti-microbial agents has always been a time-consuming and expensive process, and development of new strategies to control disease are therefore clearly warranted. The immune system has evolved to help combat various types of infections. As most pathogens enter through mucosal surfaces, the local immune defence may be of particular importance and evolutionary pressure has led to the development of a specialized immunoglobulin class in secretions—IgA. Patients with primary immunodeficiencies involving IgA are known to be highly susceptible to respiratory and gastrointestinal (GI) tract infections (for review see [1]), supporting the notion of a crucial role for antibodies in the mucosal defence. Infection-prone IgA-deficient patients are currently treated with human IgG given systemically [2]. However, a proportion of these patients still suffer from mucosal infections which necessitates development of additional forms of therapy, and human IgG in high doses has previously in fact been given orally, without adverse effects, to healthy volunteers [3] and to patients suffering from a variety of GI infections (for references see [4]). However, from a theoretical point of view human IgG is expected to be less effective than human IgA due to its comparatively low proteolytic stability, and it may also, due to its interaction with complement and phagocytosing cells, provoke an inflammatory reaction. Human breast milk, which contains secretory IgA, is known to protect against diarrhoea in infants. Oral administration of purified human immunoglobulin has previously also been suggested to exhibit a prophylactic effect against development of necrotizing enterocolitis in prematurely born children [5] and a therapeutic effect in Campylobacter jejuni [6] and Clostridium difficile [7] induced diarrhoea in immunodeficient patients as well as chronic diarrhoea of unknown aetiology in normal infants [8]. However, the titre against most human pathogens is rather low in the IgA-containing gammaglobulin preparations, and vaccination of volunteers for preparation of hyperimmune products is not feasible. Furthermore, there is always a risk of transmission of infectious agents when using human plasma as a starting material and since the cost for these preparations is high, alternative sources of antibodies must be sought. The common dairy cow may be one such alternative, as bovine antibodies are actively transported from plasma to milk in cows and are present in high concentrations in colostrum. The antibodies protect the calves from GI infections during the neonatal period and are of major importance for their survival. Bovine immunoglobulin preparations against rotavirus and Escherichia coli have previously been shown to be effective as prophylaxis against infections and have been commercially available for use in farm animals for decades. During the past few years, bovine immunoglobulin preparations have also been shown to protect against natural infection or challenge with a variety of different microorganisms in man. The effect of therapeutically administered bovine antibodies has not been as well documented, but successful intervention has been demonstrated in Helicobacter pylori, rotavirus and cryptosporidial infections (for references see [4,9]). Interaction between bovine antibodies and the human immune system is limited [10] and the preparation can be given without risk of serious adverse events. The titre of antibodies against many human pathogens is low in colostrum from non-immunized animals [4], and although a therapeutic effect has been suggested by oral administration of high doses of non-specific bovine immunoglobulins to patients with chronic diarrhoea [11–14], it is likely that a future product will have to be derived from immunized animals [10]. In this review, we will summarize published data on the use of bovine immunoglobulin-containing preparations for prophylaxis and therapy against selected mucosal infections in man and suggest directions for its future use.

Pseudomembranous Colitis Caused by C. difficile.

Pseudomembranous colitis (PMC) is a considerable clinical concern for several reasons, including disease severity, increasing frequency, complications, and development of antibiotic-resistant organisms. C. difficile infection should be considered in anyone who develops diarrhea during or after antibiotic therapy; PMC is the most serious manifestation of C. difficile disease. PMC is effectively treated with either metronidazole or vancomycin. Metronidazole should be first-line therapy, reserving vancomycin for those who are very ill or who do not respond to metronidazole or cannot take it (ie, first trimester pregnancy, side effects). Recurrent C. difficile disease (which occurs in approximately 20% of C. difficile cases) is best treated with an antibiotic in combination with a biotherapeutic agent. Prevention of epidemics of C. difficile requires careful hand washing and cleaning of environmental surfaces. Antibiotic restriction may be necessary in some cases.