amoxicillin-potassium-clavulanate-combination and Neutropenia

The science of antibiotic therapy for infectious diseases continues to evolve. In many instances where empiric coverage is necessary, treatment with more than one agent is considered prudent. If an etiology is identified, antibiotics are modified based on culture and susceptibility data. Even when the organism is known, more than one antibiotic may be needed. Decisions about antibiotics should be made after assessments of pertinent clinical information, laboratory and microbiology information, ease of administration, patient compliance, potential adverse effects, cost, and available evidence supporting various treatment options. Clinicians also need to consider synergy and local resistance patterns in selecting therapeutic options. In this article, the authors outline monotherapy and combination therapy options for several common infectious diseases.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacterial Infections; Cellulitis; Cephalosporins; Ciprofloxacin; Diverticulitis; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus faecalis; Humans; Meningitis, Bacterial; Neutropenia; Osteomyelitis; Pneumonia; Staphylococcus aureus; Viridans Streptococci

THE CONTEXT: Up until the nineties, the intravenous administration of a broad spectrum antibiotic was the classical treatment of any patient presenting with febrile neutropenia. Since then, in patients considered at low risk and with expected of neutropenia less than 7-10 days, oral antibiotherapy has become an attractive option. TWO LARGE STUDIES: A study by the antimicrobial group of the EORTC (European organisation for research and treatment of cancer) and a North American study have compared the efficacy of an oral combination of ciprofloxacine and amoxicillin/clavulanic acid with that of an intravenous antibiotherapy in low-risk patients presenting febrile neutropenia. In both studies, the success rate was the same in the group of patients treated with oral antibiotics and those treated with intravenous antibiotics. RESERVATIONS: These two studies were conducted in hospitalised patients. No conclusions can be drawn with regard to out-patient treatment. Out-patient management would only be possible after appropriate selection of patients at low risk.

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Bacterial Infections; Ceftazidime; Ciprofloxacin; Drug Therapy, Combination; Europe; Fever; Hematologic Neoplasms; Humans; Immunocompromised Host; Infusions, Intravenous; Inpatients; Multicenter Studies as Topic; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic; Risk; Treatment Outcome; United States

Neutropenic sepsis remains a common treatment complication for patients receiving systemic anti-cancer treatment. The UK National Institute for Health and Care Excellence have not recommended switching from empirical intravenous antibiotics to oral antibiotics within 48 h for patients assessed as low risk for septic complications because of uncertainty about whether this would achieve comparable outcomes to using intravenous antibiotics for longer. The UK National Institute for Health Research funded the EASI-SWITCH trial to tackle this uncertainty.. If the trial demonstrates non-inferiority of early switching to oral antibiotics, with potential benefits for patient quality of life and resource savings, this finding will have significant implications for the routine clinical management of those with low-risk neutropenic sepsis.. ISRCTN: 84288963. Registered on the 1 July 2015. https://doi.org/10.1186/ISRCTN84288963. EudraCT: 2015-002830-35.

Topics: Administration, Intravenous; Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Ciprofloxacin; Cost-Benefit Analysis; Drug Administration Schedule; Equivalence Trials as Topic; Humans; Meropenem; Multicenter Studies as Topic; Neoplasms; Neutropenia; Piperacillin; Pragmatic Clinical Trials as Topic; Quality of Life; Sepsis; Tazobactam; Treatment Outcome

Outpatient oral therapy is infrequently used in pediatric low-risk febrile neutropenia (LRFN) as there is insufficient data regarding its equivalence as compared with parenteral therapy.. This is a single institutional, randomized control trial in pediatric LRFN aged 2 to 15 years, in which 123 episodes in 88 patients were randomized to outpatient oral ofloxacin 7.5 mg/kg 12 hourly and amoxycillin-clavulanate 12.5 mg/kg 8 hourly or outpatient intravenous (IV) ceftriaxone 75 mg/kg and amikacin 15 mg/kg once daily after blood cultures.. Out of 119 evaluable episodes, one-third were leukemia patients in maintenance and rest were solid tumors. Success was achieved in 55/61 (90.16%) and 54/58 (93.1%) in oral and IV arms, respectively, (P=0.56). There were 3 hospitalizations but no mortality. Median days to resolution of fever, absolute neutrophil count >500/mm(3) and antibiotic use were 3, 5, and 6 days in both arms. There were 5 blood culture isolates (3 gram-positive and 2 gram-negative bacteria). Failure of outpatient therapy was associated with perianal infections, bacteremia, febrile neutropenia onset before day 9 of chemotherapy in solid tumors and Vincristine, actinomycin-D, and cyclophosphamide chemotherapy for rhabdomyosarcoma. All gram-positive isolates were successes, whereas both gram-negative isolates were failures. Diarrhea in IV arm and Vincristine, actinomycin-D, and cyclophosphamide chemotherapy in the oral arm predicted failure in subgroup analysis.. Outpatient therapy is efficacious and safe in pediatric LRFN. There was no difference in outcome in oral versus IV outpatient therapy. Amoxycillin-clavulanate and ofloxacin may be the oral regimen of choice.

Topics: Administration, Oral; Adolescent; Ambulatory Care; Amikacin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Ceftriaxone; Child; Child, Preschool; Drug Therapy, Combination; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Injections, Intravenous; Male; Neoplasms; Neutropenia; Ofloxacin; Treatment Outcome

Neutropenic fever is one of the most serious adverse effects of cancer chemotherapy. Neutropenia may cause a life-threatening bacterial infection. Therefore, febrile neutropenic inpatients are empirically treated with intravenous broad-spectrum antibiotics. Recently, several studies have suggested the presence of low-risk groups among febrile neutropenic patients.. A prospective randomized trial was conducted to compare treatment with oral ciprofloxacin (200 mg) and amoxicillin-clavulanate (375 mg) administered every 8 h against that with intravenous ceftazidime (1 g) administered every 12 h in low-risk febrile neutropenic patients with lung cancer. All patients received chemotherapy and antibiotic therapy while being hospitalized.. A total of 177 patients with lung cancer agreed to participate in this study prior to undergoing chemotherapy. Among them, a total of 36 neutropenic patients with 42 febrile episodes were enrolled in the study. Treatment was successful without the need for modification in 91% of the episodes in patients receiving the oral regimen and 79% of the episodes in patients receiving the intravenous regimen. No treatment-related deaths occurred. One patient developed nausea while receiving the oral regimen, so the oral regimen was changed to the intravenous regimen in this patient.. This prospective study suggested that treatment with oral antibiotics ciplofloxacin plus amoxicillin-clavulanate was effective for low-risk febrile neutropenic patients after chemotherapy.

Topics: Administration, Oral; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Infective Agents; Ceftazidime; Ciprofloxacin; Drug Therapy, Combination; Female; Fever; Humans; Infusions, Intravenous; Lung Neoplasms; Male; Middle Aged; Neutropenia; Prospective Studies; Treatment Outcome

Febrile neutropenia (FN) remains a major dose-limiting complication among patients treated with chemotherapy. Haematopoietic colony stimulating factors (G-CSF and GM-CSF) made possible a significant improvement in the management of FN, both in the therapeutic and in the prophylactic approach. The use of antibiotic prophylaxis also permits a definite reduction of severe infections during neutropenia. Nevertheless, the possible role of these two interventions for secondary prevention of FN is still unclear.. We conducted a prospective randomised trial by comparing the efficacy of granulocyte-colony stimulating factor (G-CSF) and the association of G-CSF with oral antibiotics in the secondary prevention of FN. We included in our study those patients who, after an episode of FN, continued to be treated with the same chemotherapy without reduction of dose intensity. They were randomised into two groups: the first received G-CSF (group G; filgrastim, 5 microg/kg day), and the second was treated with an association of G-CSF and amoxicillin/clavulanate plus ciprofloxacin (group G/ACC).. Forty-eight patients were randomised (group G: n=23 and group G/ACC: n=25). There was no recurrence of FN among the patients receiving G-CSF and only one episode in the combined therapy group (p=1). With regard to the side effects, there was no significant difference in the two groups.. The use of G-CSF for the secondary prevention of FN is extremely effective and allows the maintenance of chemotherapy dose intensity. Our study showed that the addition of antibiotics does not seem to be required.

Topics: Administration, Oral; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Ciprofloxacin; Drug Therapy, Combination; Female; Granulocyte Colony-Stimulating Factor; Humans; Injections, Subcutaneous; Male; Middle Aged; Neutropenia; Prospective Studies

To evaluate the effectiveness of oral amoxicillin/clavulanate (25 mg/kg every 12 h) for prevention of fever and/or infection in neutropenic children with cancer.. Multicenter, prospective, randomized, double blind placebo-controlled trial.. In the intention-to-treat analysis, amoxicillin/clavulanate had a 12% benefit increase in terms of reduction in the incidence of febrile or infectious episodes, compared with placebo [44 of 83 (53%) vs.55 of 84 (65%); 95% confidence interval, -28% to +3%; P = 0.101]. This benefit was also associated with a 30% increase in the probability of failure-free survival at Day 15 (P = 0.138). A logistic regression analysis showed the effect of prophylaxis to be relevant, especially in patients with leukemia or lymphoma and in those not receiving hematopoietic growth factors, with 17 and 15% absolute benefit increases (logistic P = 0.014 and 0.034, respectively). Compliance with oral drugs was good, with very few and nonsevere drug-related adverse events.. In this study amoxicillin/clavulanate was associated with a detectable clinical effect in the reduction of fever and infection in neutropenic children with cancer, especially those with acute leukemia and not receiving growth factors; the study was not powered to demonstrate a statistically significant effect in the overall patient population.

Topics: Adolescent; Amoxicillin-Potassium Clavulanate Combination; Antibiotic Prophylaxis; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fever; Follow-Up Studies; Humans; Infant; Male; Neoplasms; Neutropenia; Patient Compliance; Prospective Studies; Risk Assessment; Treatment Outcome

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Humans; Neutropenia

The objective of this investigation was to assess retrospectively the safety and the efficacy of oral ciprofloxacin plus cefuroxime axetil compared to the combination of oral ciprofloxacin plus amoxicillin/clavulanate, as initial outpatient treatment, in low-risk cancer patients with fever and neutropenia. We analysed retrospectively 120 episodes of febrile neutropenia, treated on an outpatient basis at 2 different oncology units; 63 episodes were treated with the oral regimen of ciprofloxacin plus amoxicillin/clavulanate and 57 were treated with the combination of oral ciprofloxacin plus cefuroxime. 20 treatment failures were recorded-2 of them among patients receiving ciprofloxacin plus amoxicillin/clavulanate and 18 in the ciprofloxacin plus cefuroxime group. Univariate analysis showed that the administration of ciprofloxacin plus cefuroxime was associated with a worse outcome compared to the regimen ciprofloxacin plus amoxicillin/clavulanate (OR 11, CI 2.42-49.9, p =0.002). In the multivariate model, after adjusting for the absolute number of neutrophils and the duration of neutropenia, the effect of the antibiotic regimen on the outcome disappeared, and no significant differences between the 2 regimens were noted, although the regimen of ciprofloxacin plus cefuroxime was associated with a trend to a worse outcome (OR 4.74, CI 0.72-31.1, p =0.10). In conclusion, the 2 regimens appeared equally safe and effective but prospective studies are needed to confirm these results.

Topics: Administration, Oral; Adult; Aged; Ambulatory Care; Amoxicillin-Potassium Clavulanate Combination; Anti-Infective Agents; Bacterial Infections; Cefuroxime; Ciprofloxacin; Drug Therapy, Combination; Female; Fever; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Retrospective Studies

BB-81384, a novel peptide deformylase (PDF) inhibitor, was characterized in terms of enzyme inhibition profile, antibacterial activity, rodent pharmacokinetics and oral efficacy in murine infection models.. MICs were determined by standard NCCLS broth microdilution. Selectivity of metalloenzyme inhibition was determined with a limited panel of enzymes via standard biochemical assays. Profiling of the pharmacokinetics and select tissue disposition in mice was determined and compared with that of the macrolide, azithromycin. In vivo murine efficacy studies using Streptococcus pneumoniae were conducted using a peritonitis model, as well as lung and thigh burden models of infection.. BB-81384 selectively inhibited PDF with an IC(50) approximately 10 nM and with MICs < 0.5 mg/L against most S. pneumoniae pathogens. Pharmacokinetic analysis revealed good oral bioavailability and moderate clearance and volume of distribution. BB-81384 partitioning to lung tissue was similar in terms of magnitude and kinetics to that of the plasma compartment. Single-administration oral efficacy in a mouse peritonitis model was evident with an ED(50) of 30 mg/kg. BB-81384 reduced the bacterial load by approximately 5 and 3 log units in organ-burden models of lung and thigh infection, respectively.. BB-81384, a novel PDF inhibitor with good activity against S. pneumoniae in vitro, was the first compound of this class to be profiled for oral pharmacokinetics and tissue disposition and to demonstrate oral anti-pneumococcal efficacy in mice.

Topics: Amidohydrolases; Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Azithromycin; Bacteria; Drug Therapy, Combination; Enzyme Inhibitors; Kinetics; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Muscle, Skeletal; Muscular Diseases; Neutropenia; Peritonitis; Piperazines; Pneumococcal Infections; Pneumonia; Streptococcus pneumoniae; Tissue Distribution

Congenital neutropenia is characterized by a severe reduction in absolute neutrophil counts, resulting in an almost total absence of neutrophils. It is well known that severe neutropenia affects periodontal status. Oral manifestations include ulcerations, gingival desquamation, gingival inflammation, attachment loss, and alveolar bone loss which may result in tooth loss. Treatment with granulocyte-colony stimulating factor (G-CSF) may improve this periodontal condition. This article reports the relationship between periodontal disease status and peripheral neutrophil levels in two consanguineous siblings with severe congenital neutropenia who did not receive routine G-CSF for 2 years prior to examination. Both siblings were given scaling, root planing, and periodontal prophylaxis in regular follow-up visits. This report demonstrates that periodontal therapy supported by adequate oral hygiene may result in restoration of neutrophil counts in siblings with congenital neutropenia.

Topics: Adolescent; Amoxicillin-Potassium Clavulanate Combination; Anti-Infective Agents, Local; Child; Chlorhexidine; Consanguinity; Dental Scaling; Drug Therapy, Combination; Female; Humans; Leukocyte Count; Male; Neutropenia; Periodontal Diseases; Siblings

Prepubertal periodontitis affects both primary and permanent dentition. The purpose of this study was to examine the composition of subgingival microflora of the permanent dentition in an 11-year-old Caucasian female, who had premature exfoliation of her deciduous teeth on her 5th year of age, and the response of this condition to the antibiotic therapy and supportive periodontal care. Gingival tissues were highly inflamed and alveolar bone loss was detected radiographically. The girl had experienced frequent upper respiratory tract infections, tonsilitis and recurrent otitis media. Her mother had history of early onset periodontitis associated with chronic idiopathic neutropenia. Blood chemistry tests and immunological examinations were also performed. Subgingival plaque samples were collected from the proximal sites of permanent molars, incisors, canines and maxillary premolars. 27 different microbial species were isolated from the subgingival microflora. Among the predominant species were Porphyromonas gingivalis (17.6%-7.3%), Prevotella intermedia (12.4%-4.7%), Capnocytophaga sputigena (14.4%-10.4%), Capnocytophaga ochracea (13.2%-6.9%) and Actinobacillus actinomycetemcomitans (9.3%-5.5%). Periodontal treatment consisted of scaling, root planing in conjunction with antibiotic administration of Augmentin 312.5 mg and Flagyl 200 mg, each t.i.d. for 10 days. 3 weeks after the antibiotic therapy, bacterial samples were collected from the same sites. All the periodontal pathogens were recovered in lower levels and A.actinomycetemcomitans was almost eliminated in the 3-week period. The evaluation of clinical indices at 3, 6 and 12 months showed that periodontal treatment in conjunction with antibiotics was effective and rapidly followed by marked clinical improvement. The microbiological monitoring at 3, 6 and 12 months after antibiotic treatment and each time prior to supportive periodontal care, revealed that the periodontal pathogens fluctuated in low levels even 12 months after treatment and could be maintained at low level by supportive periodontal care at 3-month intervals.

Topics: Aggregatibacter actinomycetemcomitans; Aggressive Periodontitis; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteria; Capnocytophaga; Child; Chronic Disease; Dental Plaque; Dental Scaling; Drug Therapy, Combination; Female; Follow-Up Studies; Gingiva; Humans; Metronidazole; Neutropenia; Porphyromonas gingivalis; Prevotella intermedia; Root Planing

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Animals; Cells, Cultured; Clavulanic Acids; Cyclophosphamide; Drug Therapy, Combination; Erythromycin; Fibroblasts; Humans; Legionella pneumophila; Legionnaires' Disease; Lung; Male; Microbial Sensitivity Tests; Neutropenia; Rats

Amoxycillin and clavulanic acid show good activity against Legionella pneumophila in vitro, and synergy has been observed between the two agents. However, in tissue culture studies, amoxycillin was inactive against intracellular legionellae, whereas clavulanic acid and amoxycillin plus clavulanic acid were as effective as erythromycin in preventing bacterial growth. These latter findings were reflected in the results of therapy of a L. pneumophila pneumonia in the neutropenic rat. Amoxycillin was ineffective in reducing bacterial counts in the lungs of infected animals, but clavulanic acid and amoxycillin-clavulanic acid produced bactericidal effects similar to those of erythromycin. The data illustrate the bactericidal activity of amoxycillin-clavulanic acid and clavulanic acid against intracellular L. pneumophila in contrast to the lack of activity of amoxycillin.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Animals; Clavulanic Acids; Disease Models, Animal; Drug Therapy, Combination; Humans; Legionella pneumophila; Legionnaires' Disease; Microbial Sensitivity Tests; Neutropenia; Rats