Discontinuation Of Antimicrobial Therapy Research Articles

#67 Treatment of Campylobacter upsaliensis and Helicobacter canis in twin brothers with XLA

Abstract Background X-linked agammaglobulinemia (XLA) is a primary immunodeficiency associated with mutations in the B cell tyrosine kinase gene leading to failure in B cell maturation, resulting in antibody deficiency and increased susceptibility to infections. Patients with XLA are at risk of severe disease with infections with Campylobacter and closely related Helicobacter species and warrant treatment with close follow up given risk of recurrence. Method We present follow up of two 5-year-old fraternal twins with XLA who were diagnosed with C. upsaliensis and H. canis respectively via microbial cell-free DNA (mcfDNA) and underwent successful treatment with multi-drug antimicrobial therapy with 12 months of follow-up. Results Patient #1 was diagnosed with XLA at 11 months of age. At 3 years of age, he presented with fever and diarrhea, with stool cultures that grew C. jejuni. Despite treatment with azithromycin, his symptoms persisted and repeat stool cultures grew C. upsaliensis. Testing via mcfDNA confirmed C. upsaliensis. Patient #2 was diagnosed with XLA at 12 months of age. He developed fever, erythema nodosum (EN) like lesions and arthritis at 3.5 years old. Given his twin’s diagnosis of Campylobacter sp. enteritis, he was given a presumptive diagnosis of Campylobacter reactive arthritis and EN. Despite treatment with Naprosyn and 14 days of azithromycin, his symptoms persisted and stool PCR was positive for Campylobacter sp. mcfDNA testing confirmed C. upsaliensis and H.canis. Given failure of initial antimicrobial therapy, both boys were treated with a 4-week course of IV ertapenem, and oral ciprofloxacin and amoxicillin, and both developed neutropenia and concern for drug toxicity. Therapy was transitioned to triple drug therapy with oral doxycycline, ciprofloxacin and amoxicillin. Doxycycline was discontinued after 3 weeks due to patients’ young age. Ciprofloxacin and amoxicillin were continued for 12 months. Both boys had complete resolution of symptoms after 12 months of therapy and remain without recurrence 10 weeks after discontinuation of antimicrobial therapy. Conclusion Physicians should be aware of the treatment challenges of chronic Campylobacter and Helicobacter infection in boys with XLA and other immunocompromised hosts. Successful treatment may require prolonged multi-drug antimicrobial therapy, with monitoring for drug toxicities.

Use of Procalcitonin to Guide Discontinuation of Antimicrobial Therapy in Patients with Persistent Intra-Abdominal Collections: A Case Series

Objective Limited evidence exists for the use of procalcitonin (PCT) to guide the duration of antimicrobial therapy in patients with intra-abdominal abscesses (IAA). In this case series, we describe clinical presentations and outcomes using PCT to guide cessation of antimicrobial therapy in patients with persistent IAA who exhibited clinical improvement. Methods A retrospective analysis of patients with IAA who had PCT levels available to review was performed in a tertiary academic teaching institution in the United States between 2017 and 2018. Demographics, clinical characteristics, and outcomes were obtained from the medical records. Patients were followed up for a minimum of 180 days after completion of antimicrobial therapy to determine if evidence of recurrence or mortality was present. Results We identified four patients with IAA. They underwent early drainage of the source of infection and received empiric antimicrobial therapy according to individual risk factors and clinical scenarios. Antimicrobials were discontinued after clinical and radiographic improvement and evidence of normal PCT levels, regardless of the persistence of fluid collections. No evidence of recurrence or mortality was observed during the follow-up period. Conclusions We found PCT to be a useful aid in the medical decision-making process to safely discontinue antimicrobial therapy in a series of patients with persistent intra-abdominal collections despite early drainage and appropriate course of antimicrobial therapy.

Discontinuation of antimicrobial therapy in adult neutropenic haematology patients: A prospective cohort

ObjectivesAntibiotics for febrile neutropenia (FN) in acute myeloid leukaemia (AML) patients undergoing intensive chemotherapy are usually maintained until neutropenia resolution, because of the risk of uncontrolled sepsis in this vulnerable population. This leads to unnecessarily prolonged antimicrobial therapy. MethodsBased on ECIL-4 recommendations, we modified our management strategy and discontinued antibiotics after a pre-established duration in patients treated for a first episode of FN between August 2014 and October 2017. ResultsAntibiotics were stopped during 62 FN episodes, and maintained in the control group (n = 13). Median age of patients was 54 years. A total of 39 (63%) patients received induction and 23 (37%) consolidation chemotherapy; 36 (58%) patients had fever of unknown origin. Median neutropenia length was 26 days (IQR 24–30). Antibiotics were started at day 9 (IQR 5–13). Most patients received piperacillin-tazobactam (56%) or cefepime (32%). Antimicrobial therapy was longer in the control group than in the policy compliant group, 10 (IQR 7–16) vs. 19 days (IQR 15–23), P = 0.0001. After antibiotics discontinuation, 20% patients experienced fever recurrence, within 5.5 days (IQR 3–7.5). None of these febrile episodes were severe and 80% patients remained afebrile, with neutrophil recovery occurring within 5 days (IQR 2–8.5). Overall, 287 antibiotics days were spared; this represents 49% of all days with antibiotics. No patient had died at day 30 from intervention; six died during late follow-up, two from graft-versus-host disease and four from relapsed or refractory leukaemia. ConclusionsDiscontinuing antibiotics in neutropenic AML patients treated for a first episode of FN is safe, and results in significant antibiotic sparing.

Efficacy of indefinite chronic oral antimicrobial suppression for prosthetic joint infection in the elderly: a comparative study

During prosthetic joint infection (PJI), surgical management is sometimes impossible and indefinite chronic oral antimicrobial suppression (ICOAS) may be the only option. The outcomes of elderly patients who benefited from ICOAS with strictly palliative intent were evaluated. A national retrospective cohort study was performed in France, involving patients aged >75 years with a PJI who were managed with planned life-long ICOAS from 2009 to 2014. Patients who experienced an event were compared to those who did not. An event was defined as a composite outcome in patients undergoing ICOAS, including local or systemic progression of the infection, death, or discontinuation of antimicrobial therapy because of an adverse drug reaction. Twenty-one patients were included, with a median age of 85 years (interquartile range 81-88 years). Eight of the 21 patients experienced an event: one had an adverse drug reaction, three had systemic progression of sepsis, and two had local progression. Two of the 21 patients died. No death was related to ICOAS or infection. There was no significant difference between the population with an event and the population free of an event with regard to demographic, clinical, and microbiological characteristics (p>0.05). ICOAS appeared to be an effective and safe option in this cohort.

Successful antimicrobial therapy and implant retention for streptococcal infection of prosthetic joints.

Streptococci cause up to 20% of prosthetic joint infections but this has received little attention in the published literature. We reviewed retrospectively our experience with treatment of streptococcal prosthetic joint infections. Patients were followed up for up to 15 years after discontinuation of antimicrobial therapy and up to 8.5 years while on continuous antimicrobial therapy. Eighteen cases were diagnosed between 1984 and 1995. These included one group A, seven group B, one group D, seven group G and one viridans-group streptococcal infection as well as one group B and D streptococcal co-infection. All were late-onset infections and most (11 of 18, 61%) were acute. Hip and knee joints were equally affected. Six of seven group G streptococcal infections were associated with skin or soft tissue infections. Sixteen patients were treated primarily with antimicrobial agents including 5 days to 6 weeks given intravenously and 2 weeks to 8.5 years given orally. At latest follow up, 10 patients had been off antimicrobial therapy for at least 18 months without relapse, one patient had been off antimicrobial therapy for 7 months without relapse and four infections were successfully controlled with long-term suppressive antimicrobial therapy. One infection was unable to be controlled with antimicrobial therapy. Our results, and those of others, show that prosthetic joint infections caused by streptococci have a relatively good outcome with primary antimicrobial therapy and, when necessary, drainage, lavage or debridement. Provided the prosthesis is stable and the patient can tolerate long-term antimicrobial therapy, this may be an effective alternative to excision arthroplasty.

The spectrum of cardiovascular infections due to Salmonella enterica: a review of clinical features and factors determining outcome.

Cardiovascular infections due to Salmonella enterica are infrequently reported, so their clinical features, prognosis, and optimal treatment are not completely known. Mortality associated with aortitis and endocarditis caused by nontyphoidal Salmonella remains exceedingly high. In this review of cases of cardiovascular infections due to Salmonella enterica studied in 2 hospitals in Madrid, we tried to assess the clinical manifestations and the procedures leading to diagnosis in addition to treatment and outcome. To complete the spectrum of infections related to cardiovascular surgery, cases of postoperative mediastinitis, pericarditis, and infections associated with cardiac devices were also included.Twenty-three patients were reviewed: 11 had mycotic aneurysms; 7 had endocarditis; 2 had device-related infections; and 3 had pericarditis, mediastinitis, and infection of an arteriovenous fistula, respectively. The risk of endovascular infection in patients older than 60 years with bacteremia due to nontyphoidal Salmonella was 23%. Most patients with aortitis had risk factors for atherosclerosis, and 6 had preexisting atherosclerotic aortic aneurysms. All except 1 patient with endocarditis had underlying cardiac disorders. Acquired immunodeficiency disease (AIDS) was a major risk factor for salmonella bacteremia in 1 patient with aortitis and 1 with endocarditis. Fever, unremitting sepsis, "breakthrough" and relapsing bacteremia were the most common clinical findings. In addition, abdominal or thoracic pain and cardiac failure and pericarditis were common features in patients with aortitis and endocarditis respectively. Computed tomography (CT) scan, arteriography, and echocardiography were the main diagnostic tools. Mortality associated with mycotic aneurysms and endocarditis due to S. enterica was 45% and 28%, respectively. Thoracic aneurysms, rupture, and shock at the time of diagnosis were associated with increased mortality in patients with aortitis. In situ bypass grafting was successfully performed in most cases. After surgery, antimicrobial therapy was continued for 4-9 weeks. No relapses were observed after a mean follow-up of 64 months. Antimicrobial therapy alone or combined with valve replacement or excision of a ventricular aneurysm was successful treatment for most patients with salmonella endocarditis. Combined medical and surgical treatment was required for patients with mediastinitis and pericarditis, and patients with device-related infections needed removal of the complete device. Diagnosis of aortitis due to nontyphoidal Salmonella should be established as early as possible to reduce mortality. Patients older than 60 years who have positive blood cultures for Salmonella along with fever and back, abdominal, or chest pain should have an extensive workup for infective aortitis. Immediate bactericidal antimicrobial therapy should be started and a CT scan should be performed on an emergency basis. If a mycotic aneurysm is found, surgical resection should follow as soon as possible. Resection of the aneurysm with in situ bypass grafting is the procedure of choice. Postoperative antimicrobial therapy for 6-8 weeks seems enough to avoid relapses. Optimal treatment of patients with endocarditis occurring on ventricular aneurysms must include resection of the aneurysmal sac. Salmonella endocarditis can be successfully treated with antimicrobials alone. Valve replacement should be reserved for patients with cardiac failure or persisting sepsis, and for those who relapse after discontinuation of antimicrobial therapy.

Fever and neutropenia in children with malignant disease.

Treatment of episodes of fever and neutropenia in pediatric hematology-oncology patients includes hospitalization and administration of intravenous antibiotics until the patient is afebrile and no longer neutropenic. The present analysis characterizes retrospectively febrile episodes in neutropenic pediatric hematology-oncology patients with regard to frequency of documented infections, organisms associated with these infections, efficacy of a standardized antibiotic regimen, and safety of early antibiotic discontinuation under defined conditions. A total of 149 pediatric febrile neutropenic episodes were identified during a 4-year period between 1990 and 1994. These occurred in 47 male and 19 female patients, of a mean age of 7.6 years (range 0.5-15). The most frequent diagnoses were leukemia (41% of patients), lymphoma (21%), rhabdomyosarcoma (7%), soft tissue sarcoma (5%), Ewing's sarcoma (5%), and osteosarcoma (4%). Infection was certain in 36% of febrile episodes, probable in 14%, and not determined in 50%. Patients with severe neutropenia (absolute neutrophil count < 100) had a slightly, although not significantly higher incidence of documented and probable infection (57%). Patients with solid tumor had documented infection in 40% of their febrile episodes, and the detection rate in the children with leukemia was 31% (P < .20) Blood cultures were positive in 21 (14%) of 149 episodes. Staphylococci (both coagulase-negative and coagulase-positive strains) and Pseudomonas were the organisms most frequently isolated (six episodes each). Mouth and throat (11), lungs (10), and skin (10) were the next most frequent sites of localized infection. Initial treatment consisted of piperacillin and amikacin or of vancomycin and amikacin when the source of fever was thought to be an infected central line catheter, with addition of amphotericin B by the seventh day of treatment when fever with neutropenia persisted or upon clinical suspicion of underlying fungal infection. There was a single fatality, of a patient with Burkitt's lymphoma. Antibiotics were discontinued when initial blood cultures had no growth after at least 48 hours and no source of infection was found, the blood count was improving, and if the patient became afebrile and clinically well. No patient needed readmission during the fortnight that followed discontinuation of antimicrobial therapy. Patients with negative blood cultures under defined conditions, as described above, could safely be discharged early, thus shortening the duration of intravenous antibiotic therapy and hospital stay.

Oral ofloxacin as treatment of malignant external otitis: A study of 17 cases

Seventeen patients with malignant external otitis were treated with oral ofloxacin. Their mean age was 69 years. Seven of the patients were diabetic. Pseudomonas aeruginosa, sensitive to ofloxacin (Kirby-Bauer method, inhibition zone greater than or equal to 22 mm), was isolated from the external auditory canal in all patients. Ofloxacin (200 mg b.i.d.) was given to the patients for 12 to 39 days. Two patients also received additional parenteral antibiotic therapy. Subjective and objective improvement occurred in all patients during treatment, and complete resolution was documented in all patients, with one exception. Only one patient suffered recurrence 2 weeks after discontinuation of antimicrobial therapy. The results of our study suggest that oral ofloxacin is an effective treatment for malignant external otitis caused by Pseudomonas aeruginosa.

1081 NEONATAL SEPSIS: PREDICTIVE VALUE OF 48 HOUR CULTURE RESULTS

Traditionally, antimicrobial therapy is discontinued in neonates with suspected sepsis when the cultures are reported negative at 72 hours. Rising hospitalization costs and the trend towards early discharge led us to examine the reliability of 48 hour culture results as a guide towards discontinuation of antimicrobial therapy. In a two-part study (Retrospective 69 months; Prospective 2 months), 48 and 72 hour reports of blood and cerebrospinal fluid (CSF) cultures from term neonates were evaluated. The following pathogens were isolated: Group B and D Streptococcus, E. coli, Enterococcus, H. influenzae, and Streptococcus pneumoniae. The single blood culture that was reported positive at 72 hrs but not at 48 hrs was due to H. influenzae; this symptomatic infant received a full course of antibiotics. Discontinuation of antibiotic therapy in clinically well infants based on 48 hr culture results does not appear to compromise quality of medical care and could even facilitate early discharge of term neonates.