This is the first in a series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. The purpose of these guidelines is to provide assistance to clinicians when making decisions on treating the conditions specified in each guideline. The targeted providers are internists, pediatricians, and family practitioners. The targeted patients and setting for the fever and neutropenia guideline are hospitalized individuals with neutropenia secondary to cancer chemotherapy. Panel members represented experts in adult and pediatric infectious diseases and oncology. The guidelines are evidence-based. A standard ranking system was used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council. An executive summary, algorithms, and tables highlight the major recommendations. The guideline will be listed on the IDSA home page at http://www.idsociety.org.

/pdf/1997-guidelines-for-the-use-of-antimicrobial-agents-in-1wxhwgdaus.pdf

1997 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Unexplained Fever

Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: An EORTC double-blind placebo-controlled phase III study

Ovarian cancer is characterized by dysbiosis, referred to as oncobiosis in neoplastic diseases. In ovarian cancer, oncobiosis was identified in numerous compartments, including the tumor tissue itself, the upper and lower female genital tract, serum, peritoneum, and the intestines. Colonization was linked to Gram-negative bacteria with high inflammatory potential. Local inflammation probably participates in the initiation and continuation of carcinogenesis. Furthermore, local bacterial colonies in the peritoneum may facilitate metastasis formation in ovarian cancer. Vaginal infections (e.g. Neisseria gonorrhoeae or Chlamydia trachomatis) increase the risk of developing ovarian cancer. Bacterial metabolites, produced by the healthy eubiome or the oncobiome, may exert autocrine, paracrine, and hormone-like effects, as was evidenced in breast cancer or pancreas adenocarcinoma. We discuss the possible involvement of lipopolysaccharides, lysophosphatides and tryptophan metabolites, as well as, short-chain fatty acids, secondary bile acids and polyamines in the carcinogenesis of ovarian cancer. We discuss the applicability of nutrients, antibiotics, and probiotics to harness the microbiome and support ovarian cancer therapy. The oncobiome and the most likely bacterial metabolites play vital roles in mediating the effectiveness of chemotherapy. Finally, we discuss the potential of oncobiotic changes as biomarkers for the diagnosis of ovarian cancer and microbial metabolites as possible adjuvant agents in therapy.

/pdf/the-role-of-the-microbiome-in-ovarian-cancer-mechanistic-4gkgt1v79p.pdf

The role of the microbiome in ovarian cancer: mechanistic insights into oncobiosis and to bacterial metabolite signaling.

Background: The administration of chemotherapy is associated with risk for morbidity. Management of chemotherapy-related morbidity in veterinary oncology has been primarily supportive.



Hypothesis: The purpose of this study was to evaluate the effect of prophylactic antimicrobial use on chemotherapy-associated morbidity in dogs with lymphoma or osteosarcoma.



Animals: Dogs presenting with histologically confirmed osteosarcoma or lymphoma were eligible.



Methods: Patients were randomized to receive placebo or trimethoprim-sulfadiazine for 14 days after their first doxorubicin chemotherapy. Both owner and clinician were blinded with respect to treatment. Patient assessment included CBC, physical examination and performance, and toxicosis grading on days 7 and 14. Investigated outcomes were hospitalization, suspicion of infection, gastrointestinal toxicity, neutropenia, nonhematologic toxicity, and quality of life.



Results: Seventy-three dogs were enrolled; 34 had osteosarcoma, and 39 had lymphoma. Dogs receiving trimethoprim-sulfadiazine (n = 36) had a significantly reduced hospitalization rate (P=.03), nonhematologic toxicity (P= 0.039), grade 2–4 nonhematologic toxicity (P < .0001), grade 2–4 gastrointestinal toxicity (P= .007). and altered performance (P= .015). By group, dogs with osteosarcoma (n = 34) that received the antimicrobial experienced fewer occurrences of nonhematologic toxicity (P= .02) and less severe nonhematologic toxicity (P= .038). Dogs with lymphoma (n = 39) had significant reductions in the occurrence of hospitalization (P= .035), severity of nonhematologic toxicity (P= .036), and alterations of performance (P= .015).



Conclusions: The use of prophylactic trimethoprim-sulfadiazine has benefit in reducing morbidity in dogs with osteosarcoma or lymphoma during the first 14 days after treatment with doxorubicin.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1939-1676.2007.tb02940.x

Prophylactic trimethoprim-sulfadiazine during chemotherapy in dogs with lymphoma and osteosarcoma: a double-blind, placebo-controlled study.

Bacterial sepsis remains a major cause of morbidity and mortality in patients rendered neutropenic following cyto- reductive therapy for haematological malignancy. The introduction of more aggressive anti-neoplastic chemo- therapeutic regimes in individuals with solid organ malig- nancies has resulted in increasing numbers of these patients experiencing the profound neutropenia (i.e. granulocyte counts of 0.1 10 9 /L) that puts them at risk of infection. It is now over 30 years since Bodey et al. , in a landmark paper, 1 first quantified the risk of infection associated with severe neutropenia. Throughout this period much effort and considerable economic resources have been expended on developing effective approaches to prevent infection by bacteria and other microorganisms in this setting. Many of these strategies have fallen out of favour, having foundered on grounds of expense, patient unacceptability and conse- quent problems with compliance, and a lack of convincing scientific evidence to support their efficacy. One practice that has proved more durable than most is the use of antibacterial prophylaxis (ABP). This approach is not without its detractors and, given the problems attributed to ABP that have emerged in recent years, a re-examination of its risks and benefits is warranted. When ABP was first introduced, Gram-negative bac- teria—particularly members of the Enterobacteriaceae and Pseudomonas aeruginosa—were the most important bacterial pathogens encountered in neutropenic patients; infections were associated with significant case-fatality rates. Many of these bacteraemias were deemed to be autocthonous in origin, with the gut being the most likely source. The concept of 'colonization resistance', which underpinned the rationale for ABP, was developed by van der Waaij and co-workers 2 (reviewed in reference 3) following observations in laboratory animals. Mice with their own normal gut flora were able to resist colonization when challenged by exogenous Gram-negative aerobic bacteria, unless these were administered in very high doses. Conversely, in gnotobiotic mice, colonization was achieved by inocula of 10-100 organisms. Germ-free mice that had first been colonized by anaerobic flora were able to resist colonization nearly as well as normal controls. Extra- polating this concept to humans, it was argued that preven- tion of infection from gut-derived Gram-negative bacteria during neutropenia could be achieved by administering antimicrobials that would selectively target these bacteria and that would leave the 'beneficial' anaerobes intact. Initial regimens comprised cocktails of orally administered non-absorbable antibacterials, often in conjunction with a polyene antifungal. Frequently, these agents were used in combination with oral antiseptics. These protocols were problematic to administer and patient compliance was poor. Experience with this approach to ABP was mixed and results derived from published studies are difficult to analyse because of differences in the combinations used, the frequency of administration of the agents involved, and in the degree and duration of neutropenia experienced by trial subjects. In addition, there were variations in the timing of commencement of ABP relative to the onset of neutropenia and also in adjunctive measures such as dietary manipulation or nursing of patients in laminar air flow environments.

/pdf/the-prophylaxis-of-bacterial-infections-in-neutropenic-1rev1ddjyw.pdf

The prophylaxis of bacterial infections in neutropenic patients.

Chemoprophylaxis with oral ciprofloxacin in ovarian cancer patients receiving taxol.

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Chemoprophylaxis with oral ciprofloxacin in ovarian cancer patients receiving taxol.