BackgroundEvidence suggests that the gut microbiota play an important role in gastrointestinal problems.AimTo give clinicians a practical reference guide on the role of specified probiotics in managing particular lower gastrointestinal symptoms/problems by means of a systematic review-based consensus.MethodsSystematic literature searching identified randomised, placebo-controlled trials in adults; evidence for each symptom/problem was graded and statements developed (consensus process; 10-member panel). As results cannot be generalised between different probiotics, individual probiotics were identified for each statement.ResultsThirty seven studies were included; mostly on irritable bowel syndrome [IBS; 19 studies; treatment responder rates: 18–80% (specific probiotics), 5–50% (placebo)] or antibiotic-associated diarrhoea (AAD; 10 studies). Statements with 100% agreement and ‘high’ evidence levels indicated that: (i) specific probiotics help reduce overall symptom burden and abdominal pain in some IBS patients; (ii) in patients receiving antibiotics/Helicobacter pylori eradication therapy, specified probiotics are helpful as adjuvants to prevent/reduce the duration/intensity of AAD; (iii) probiotics have favourable safety in patients in primary care. Items with 70–100% agreement and ‘moderate’ evidence were: (i) specific probiotics help relieve overall symptom burden in some patients with diarrhoea-predominant IBS, and reduce bloating/distension and improve bowel movement frequency/consistency in some IBS patients and (ii) with some probiotics, improved symptoms have led to improvement in quality of life.ConclusionsSpecified probiotics can provide benefit in IBS and antibiotic-associated diarrhoea; relatively few studies in other indications suggested benefits warranting further research. This study provides practical guidance on which probiotic to select for a specific problem.

SummaryBackgroundIn 2013, a systematic review and Delphi consensus reported that specific probiotics can benefit adult patients with irritable bowel syndrome (IBS) and other gastrointestinal (GI) problems.AimTo update the consensus with new evidence.MethodsA systematic review identified randomised, placebo‐controlled trials published between January 2012 and June 2017. Evidence was graded, previously developed statements were reassessed by an 8‐expert panel, and agreement was reached via Delphi consensus.ResultsA total of 70 studies were included (IBS, 34; diarrhoea associated with antibiotics, 13; diarrhoea associated with Helicobacter pylori eradication therapy, 7; other conditions, 16). Of 15 studies that examined global IBS symptoms as a primary endpoint, 8 reported significant benefits of probiotics vs placebo. Consensus statements with 100% agreement and “high” evidence level indicated that specific probiotics help reduce overall symptom burden and abdominal pain in some patients with IBS and duration/intensity of diarrhoea in patients prescribed antibiotics or H. pylori eradication therapy, and have favourable safety. Statements with 70%‐100% agreement and “moderate” evidence indicated that, in some patients with IBS, specific probiotics help reduce bloating/distension and improve bowel movement frequency/consistency.ConclusionsThis updated review indicates that specific probiotics are beneficial in certain lower GI problems, although many of the new publications did not report benefits of probiotics, possibly due to inclusion of new, less efficacious preparations. Specific probiotics can relieve lower GI symptoms in IBS, prevent diarrhoea associated with antibiotics and H. pylori eradication therapy, and show favourable safety. This study will help clinicians recommend/prescribe probiotics for specific symptoms.

Over a 7-year period, we analyzed 261 dose regimens of antimicrobial drugs in the treatment and prevention of Pneumocystis carinii pneumonia in an immunosuppressed rat model. These compounds ranged from drugs in clinical use to newly synthesized agents. Drug efficacy was expressed as the magnitude of the reduction in median P. carinii cyst or nucleus counts on a scale ranging from inactive (<5-fold) to very markedly active (.1,000-fold). The classification system was reproducible and allowed drugs studied at different times to be compared with each other. The system demonstrated a hierarchy of anti-P. carinii activity not only among classes of compounds but also among individual members of a drug class. Sulfonamides, sulfones, and diamidines were the most active agents; some purine nucleosides and nitrofurans also showed promising activity; and most antiparasitic, antifungal, antibacterial, and antiviral drugs were inactive. We conclude that this classification system represents a simple, quantitative method of comparing the activities of antimicrobial drugs against P. carinii. Information gained from this system should be helpful in developing new anti-P. carinii compounds and establishing standard procedures for their evaluation.Over the past decade, there has been a major rise in the number of cases of Pneumocystis carinii pneumonia associated with AIDS. The well-publicized limitations of currently available anti-P. carinii drugs in AIDS patients have emphasized the need for new therapeutic approaches (37). Most drug testing has been performed in an immunosuppressed rat model of pneumocystosis, which accurately predicts activity against human P. carinii. Compounds which have exhibited anti-P. carinii activity in the rat model include antifolate drugs (alone or in combination) such as dihydrofolate reductase (DHFR) inhibitors, sulfonamides, sulfones, and sulfonylureas (7, 9, 12, 14, 16-20, 23, 24, 27, 35, 39, 42, 43); sulfonamides in combination with other drugs (e.g., macrolides) (13); diamidines and related cationic compounds (8,11,21,34,40); 8-aminoquinolones, alone or in combination with other agents (1, 28); purine nucleosides (la, 32, 36); polyamine inhibitors (3, 4); nitrofurans (38); 3-glucan inhibitors (26, 29, 30); hydroxynaphthoquinones (14); fluoroquinolones (2); iron chelators (4); and immunological agents (antibodies, cytokines) (10,31).Although the rat model has been very valuable, evaluation of anti-P. carinii drugs is time-consuming, expensive, and labor intensive; only a few compounds can be tested in a given experiment. Treatment studies have been performed by different experimental protocols and methods of evaluating drug efficacy; this lack of standardization has prevented the results of one investigator from being compared directly with those of another. Little attention has also been devoted to quantitating the reduction in organism burden which can be achieved with different doses of anti-P. carinii drugs. In addition, there have been few published sources of information of the compound...

The efficacy of antifolate, antiviral, and other drugs was compared in an experimental model of pneumocystosis. Sulfamethoxazole (SMX) administered alone in doses of .60 mg/kg/day was highly effective in treatment and prophylaxis. Low (c15 mg/kg/day) doses of SMX showed limited, dose-related antiPneumocystis carinii activity in therapy but were more effective in prophylaxis. The dihydrofolate reductase (DHFR) inhibitors trimethoprim (TMP), pyrimethamine, and trimetrexate exhibited little anti-P. carinii activity when administered alone and did not enhance the efficacy of SMX; the effects of the DHFR inhibitors could not be related to the dose or the concentration in serum. These data suggested that the rat model is an excellent system for studying the anti-P. carinii activity of sulfonamides but is of limited value in studying DHFR inhibitors. The antiviral drugs azidothymidine, dideoxyinosine, inosine pranobex (Isoprinosine), amantadine, and acyclovir displayed little or no activity against P. carinii; however, azidothymidine did not impair the efficacy of SMX or TMP-SMX. These results supported the clinical practice of giving antiviral agents together with antifolate drugs to patients infected with human immunodeficiency virus and suggested that the beneficial effects of antiviral agents on the occurrence of pneumocystosis are due mainly to their effects on the virus or the host immune response. In contrast to the antiviral drugs, 9-deazainosine, a nucleoside analog with antiprotozoal properties, deinonstrated marked activity against P. carinii which was related to dose and route of administration. These data raised the possibility that anti-P. carinii activity is a general property of purine nucleosides Experimental studies of anti-P. carinii drugs have usually been performed in an immunosuppressed rat model of pneumocystosis, which is a reliable predictor of activity against the human form of the disease (10,13,20). In a previous study of antifolate drugs in this model (34), we found that anti-P. carinii activity was a general property of sulfonamides; these compounds were so effective that a doseresponse curve could not be established at the doses used. By contrast, DHFR inhibitors exhibited little anti-P. carinii activity and did not improve the efficacy of the sulfonamides * Corresponding author.or the sulfone dapsone. This lack of synergism differed from the results of previous workers (10,14,15) and raised questions about the value of using the rat model to screen antifolate drugs.In the present study, we have extended these observations by exploring the effect of lower doses of the sulfonamide sulfamethoxazole (SMX) in the therapy of experimental pneumocystosis. We

Inhibitors of folic acid synthesis were compared alone and in different combinations in the therapy of pneumocystosis in immunosuppressed rats. Sulfonamides (sulfamethoxazole, sulfadiazine, and sulfadoxine) and sulfones (dapsone) used alone were very active against Pneumocystis carinii, as judged by histologic examination of the lungs and by organism quantitation. Improved efficacy could not be demonstrated by the addition of an inhibitor of dihydrofolate reductase to the regin1en. Dihydrofolate reductase inhibitors (trimethoprim, diaveridine, and pyrimethamine) used alone were ineffective against P. carinii. All drugs were well tolerated except pyrimethamine, which caused bone marrow depression; folinic acid ameliorated this adverse reaction but did not interfere with P. carinii treatment. These data have potential clinical implications but need to be interpreted with caution and in light of other systems of P. carinii drug evaluation.