Days Of Parenteral Therapy Research Articles

1148. Duration of Antibiotic Therapy in the Treatment of Bacterial Meningitis in Young Infants: A Systematic Review and Narrative Synthesis

BackgroundIDSA recommendations of 14-21 days of parenteral therapy for bacterial meningitis are based predominantly on expert consensus. Parenteral durations consistent with these recommendations are sometimes provided even when meningitis is suspected but not confirmed. We aimed to systematically review the literature on duration of parenteral antibiotic therapy and outcomes in bacterial meningitis in infants < 3 months of age.MethodsWe searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for publications up until May 11, 2021. Eligible studies were published in English and included infants < 3 months of age with bacterial meningitis for which route and duration of antibiotic therapy and outcomes were reported. We excluded case reports and infants with birth weight < 1500g, major congenital malformations, or neurosurgical conditions. We assessed bias using published tools specific to study type. A meta-analysis was not conducted due to insufficient data on outcomes by duration of therapy. PROSPERO registration: CRD42020201667.ResultsA total of 2195 studies were identified; 280 were selected for full text review and 32 were included for narrative synthesis. There was 1 randomized-controlled trial (RCT), 25 cohort studies, and 6 case series. The RCT found no difference in treatment failure rates between 10 and 14 days of therapy, but only included 2 cerebrospinal fluid (CSF) culture-positive cases. A single cohort study including only CSF culture-negative cases presented outcomes by duration of therapy and concluded that courses >21 days had no impact on prognosis. Twenty-one studies had data on duration of therapy and outcomes by patient, most with small samples (median 4 patients). No conclusions on efficacy of shortened antibiotic courses could be drawn due to small sample sizes and lack of stratification of outcomes by short versus long courses.ConclusionData on parenteral treatment duration in bacterial meningitis in infants < 3 months are primarily observational, and larger studies rarely report outcomes by duration of therapy. Given the associated risks and costs of prolonged parenteral therapy, there is a pressing need for comparative effectiveness research to determine the optimal parenteral treatment duration.Disclosures All Authors: No reported disclosures

Efficacy and Cost Comparison of Ertapenem as Outpatient Parenteral Antimicrobial Therapy in Acute Pyelonephritis due to Extended-spectrum Beta-lactamase-producing Enterobacteriaceae.

Outpatient parenteral antimicrobial therapy (OPAT) programs are becoming an increasingly popular trend in clinical practice as they offer several benefits to both patients and health-care setups. While OPAT is an established clinical practice in the Western world, the concept itself is alien to patients in India as they prefer the security of hospitals to receive antibiotics over OPAT. We evaluated the clinical response and cost comparison of ertapenem under OPAT versus inpatient settings in patients with extended-spectrum beta-lactamase (ESBL)-positive acute pyelonephritis (APN) given the increasing importance of optimizing both hospital beds and overall cost of patient care in India. APN was chosen as the indication to be studied as it is one of the common complicated urinary tract infections treated in our OPAT unit requiring 10–14 days of parenteral therapy with an agent active against various Gram-negative bacilli and multidrug-resistant organisms. One hundred patients were retrospectively studied based on whether antibiotics were administered during hospital stay alone (hospital only), during both hospital stay, and also as OPAT post discharge (hospital/OPAT) or as OPAT alone (OPAT only). Response to ertapenem and cost of treatment in inpatient versus OPAT settings were compared using Pearson's Chi-square or Fisher's exact test for categorical variables. ANOVA (or Kruskal–Wallis) was used for continuous variables. Baseline urine cultures were ESBL positive with 98% prevalence of Gram-negative bacilli (GNB). Colony counts were ≥100,000 in 74% patients. Only ertapenem, imipenem, and meropenem showed 100% sensitivity to ESBL-positive GNB in baseline urine culture and sensitivity reports. Ertapenem showed 100% sensitivity and complete clinical resolution for 96% patients with APN due to ESBL Enterobacteriaceae. It was administered as OPAT in 90% patients and significantly reduced overall treatment costs.

Ertapenem versus cefepime for initial empirical treatment of pneumonia acquired in skilled-care facilities or in hospitals outside the intensive care unit

The study presented here compared the efficacy and safety of ertapenem and cefepime as initial treatment for adults with pneumonia acquired in skilled-care facilities or in hospital environments outside the intensive care unit (ICU). Non-ventilated patients developing pneumonia in hospital environments outside the ICU, in nursing homes, or in other skilled-care facilities were enrolled in this double-blind non-inferiority study, stratified by APACHE II score (<or=15 vs >15) and randomized (1:1) to receive cefepime (2 g every 12 h with optional metronidazole 500 mg every 12 h) or ertapenem (1 g daily). After 3 days of parenteral therapy, participants demonstrating clinical improvement could be switched to oral ciprofloxacin or another appropriate oral agent. Probable pathogens were identified in 162 (53.5%) of the 303 randomized participants. The most common pathogens were Enterobacteriaceae, Streptococcus pneumoniae, and Staphylococcus aureus, isolated from 59 (19.5%), 39 (12.9%), and 35 (11.6%) participants, respectively. At the test-of-cure assessment 7-14 days after completion of all study therapy, pneumonia had resolved or substantially improved in 89 (87.3%) of 102 clinically evaluable ertapenem recipients and 80 (86%) of 93 clinically evaluable cefepime recipients (95% confidence interval for the difference, -9.4 to 11.8%), fulfilling pre-specified criteria for statistical non-inferiority. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. In this study population, ertapenem was as well-tolerated and efficacious as cefepime for the initial treatment of pneumonia acquired in skilled-care facilities or in hospital environments outside the ICU.

Diagnosis and management of catheter‐related bloodstream infections due to Staphylococcus aureus

Intravenous catheters are essential to modern medical care but frequently cause complications, the most important of which is infection, commonly due to Staphylococcus aureus. It is estimated at least 3000 episodes of catheter-related bloodstream infection occur annually in Australia, and 9% to 25% of patients with such infections die. Infection rates vary depending on the type of device, with the lowest rates associated with peripherally inserted central catheters and highest rates with haemodialysis catheters. In febrile patients, the presence of an intravenous catheter should always prompt consideration of whether the line is the source, even if there is no exit site inflammation. If catheter-related infection appears likely, the line should be removed if possible. Either peripheral and line tip cultures, or timed cultures of blood drawn peripherally and through the line, should be taken. Empirical antibiotics should be aimed at S. aureus and aerobic Gram-negative organisms, and blood cultures should be repeated at 72 h. If S. aureus is grown, cure requires removal of the catheter, at least 14 days of parenteral therapy, and consideration of echocardiography (preferably transoesophageal). If the patient remains febrile for >72 h, blood cultures at 72 h grow S. aureus, or there is a prosthetic heart valve, the risk of endocarditis is high and 6 weeks of parenteral therapy should be given. Prevention requires an organized system of surveillance, with a strict policy on insertion of central lines in controlled conditions and regimented catheter care. The role of impregnated catheters in prevention remains controversial.

A prospective, randomized, double-blind multicenter comparison of parenteral ertapenem and ceftriaxone for the treatment of hospitalized adults with community-acquired pneumonia

Background: Ertapenem is a once-daily parenteral beta-lactam licensed in the United States in November 2001 and in Europe in May 2002. Objective: This study compared the efficacy and safety profiles of ertapenem with those of ceftriaxone for the treatment of hospitalized adult patients with serious community-acquired pneumonia (CAP) requiring parenteral therapy. Methods: In this prospective, double-blind (with sponsor blinding), multicenter study, adult patients with CAP were stratified by Pneumonia Severity Index (≤3 or >3) and age (≤65 or >65 years) and randomized (2:1) to receive IV or intramuscular (IM) ertapenem 1 g once daily or IV or IM ceftriaxone 1 g once daily. Investigators could switch patients to an oral antimicrobial agent if clinical improvement was shown after at least 3 days of parenteral therapy. Results: A total of 364 patients were randomized to treatment: 239 to the ertapenem group and 125 to the ceftriaxone group. Three patients in the ertapenem group and 2 in the ceftriaxone group did not receive study therapy. Of the treated patients, 77.1% (182/236) of patients in the ertapenem group and 75.6% (93/123) in the ceftriaxone group were clinically evaluable. Among clinically evaluable patients, the mean (SD) durations of parenteral and total (parenteral plus optional oral) therapy were 5.5 (2.6) and 11.5 (2.7) days for ertapenem and 5.6 (2.8) and 11.7 (3.0) days for ceftriaxone, respectively. Streptoccocus pneumoniae was the most frequently isolated pathogen in both treatment groups. Cure rates were 92.2% for clinically evaluable patients in the ertapenem group and 93.6% for those in the ceftriaxone group (95% CI for the difference, adjusted for stratum, −8.6 to 5.7), fulfilling the criteria for statistical equivalence. At completion of parenteral therapy, 94.7% of patients in the ertapenem group and 95.8% in the ceftriaxone group showed clinical improvement. Infused vein complications (ertapenem, 3.4% [8/236]; ceftriaxone, 7.3% [9/123]) and elevated transaminase levels (ertapenem, 6.3% [13/207]; ceftriaxone, 7.1% [8/113]) were the most common adverse events in both groups. Conclusions: In this study of hospitalized adult patients, ertapenem therapy, with an oral switch option, was as effective as ceftriaxone with the same oral switch option for treatment of CAP requiring initial parenteral therapy. The overall safety profiles of the 2 drugs were comparable.

A shortened course of parenteral antibiotic therapy in the management of acute septic arthritis of the hip.

We reviewed 20 consecutive patients with a culture-proven acute septic arthritis of the hip who were treated with a shortened course of parenteral antibiotic therapy after a surgical drainage. Patients were switched over to an oral antibiotic when they showed clinical improvement. Sixteen of the 20 patients had parenteral antibiotic therapy of <10 days, whereas nine of these patients received <7 days of parenteral therapy (mean, 8.2 days). No recurrence of infection, readmission, or osteomyelitis was observed after the discharge. At the follow-up interview (mean, 32 months), 18 patients were completely asymptomatic, and two patients had occasional hip pain with activity but no physical limitations. All 20 patients had normal hip range of motion and gait. Their latest radiographs (mean, 26 months) revealed 11 patients with normal findings, six patients with mild coxa magna, and three patients with a smaller ossific nucleus compared with the unaffected side. We conclude that a community-acquired, acute gram-positive septic arthritis of the hip can be managed safely with a surgical drainage and a shortened course of parenteral antibiotic therapy, which can be switched over to an oral therapy based on the patient's response to the therapy.

A Shortened Course of Parenteral Antibiotic Therapy in the Management of Acute Septic Arthritis of the Hip

Summary We reviewed 20 consecutive patients with a culture-proven acute septic arthritis of the hip who were treated with a shortened course of parenteral antibiotic therapy after a surgical drainage. Patients were switched over to an oral antibiotic when they showed clinical improvement. Sixteen of the 20 patients had parenteral antibiotic therapy of <10 days, whereas nine of these patients received <7 days of parenteral therapy (mean, 8.2 days). No recurrence of infection, readmission, or osteomyelitis was observed after the discharge. At the follow-up interview (mean, 32 months), 18 patients were completely asymptomatic, and two patients had occasional hip pain with activity but no physical limitations. All 20 patients had normal hip range of motion and gait. Their latest radiographs (mean, 26 months) revealed 11 patients with normal findings, six patients with mild coxa magna, and three patients with a smaller ossific nucleus compared with the unaffected side. We conclude that a community-acquired, acute gram-positive septic arthritis of the hip can be managed safely with a surgical drainage and a shortened course of parenteral antibiotic therapy, which can be switched over to an oral therapy based on the patient's response to the therapy.

Successful Topical Treatment of Murine Cutaneous Leishmaniasis with a Combination of Paromomycin (Aminosidine) and Gentamicin

Cutaneous leishmaniasis is presently treated with 20 days of parenteral therapy with a frequently toxic drug (antimony). Topical formulations of paromomycin (15%) plus methylbenzethonium chloride (MBCL, 12%) or plus urea (10%) in soft white paraffin have been tested for Old and New World disease in humans. We compared the efficacy of a new topical formulation, WR 279,396 (paromomycin [15%] plus gentamicin [0.5%]) to the clinical formulations in the treatment of cutaneous disease in BALB/c mice. Sixty-day-old lesions were treated twice a day for 10 days, and the response to therapy was determined over a further 70 days. For ulcers due to Leishmania major or to Leishmania mexicana, 100% of lesions in the WR 279,396 group healed by day 20 after therapy and did not relapse by day 70; 83% of lesions healed without relapse in the paromomycin-MBCL group. In the paromomycin-urea group, 100% of L. major lesions healed by day 30 but 30% relapsed. For ulcers due to Leishmania panamensis or Leishmania amazonensis, all lesions treated with WR 279,396 healed and did not relapse; < 50% of lesions treated with paromomycin-MBCL healed by day 30, and all lesions relapsed by day 70. In addition to being active, WR 279,396 was not toxic in this model and appears to have a cosmetic effect (promoting hair growth, healing, and limiting the size of the scar).

Sequential therapy in the hospital management of lower respiratory infections

Conventional treatment for patients hospitalized with lower respiratory infections, such as pneumonia or bronchitis, typically consists of parenteral antibiotic therapy for 7-10 days. The clinical evidence, however, shows that in most patients the objective and subjective indicators of infection are substantially improved within the first 2 days of treatment. Thus, many of these patients can be switched to oral antibiotics after 2-3 days of parenteral therapy, with no loss in efficacy of treatment and with substantial savings in terms of cost of care and length of hospital stay. beta-Lactam antibiotics are a frequent choice for the oral component following short-term intravenous therapy. The results of recent, large-scale comparative clinical trials support the usefulness of this treatment approach, known as sequential therapy.

Eflornithine Treatment of Refractory Pneumocystis carinii Pneumonia in Patients with Acquired Immunodeficiency Syndrome

Eflornithine was offered as compassionate treatment of 33 episodes of Pneumocystis carinii pneumonia in 31 patients with acquired immunodeficiency syndrome who were intolerant of and/or unresponsive to conventional trimethoprim-sulfamethoxazole or pentamidine therapy. A full course of eflornithine consisted of ten days at 400 mg/kg/d but no more than 30 g/d in four divided intravenous doses, four days at 300 mg/kg/d in four divided intravenous doses, and then up to six weeks at 300 mg/kg/d in four divided oral doses where tolerated. Of 33 patient-episodes, 15 patients were discharged from the hospital without need for supplemental oxygen after receiving ten or more days of parenteral therapy and were classified as responders. Of the 16 episodes classified as treatment failures, death occurred within the first 10 days of therapy in 12, and supplemental oxygen could not be withdrawn in 4. The other two patients left the hospital without need of oxygen after receiving one and six days of treatment with eflornithine and were not considered evaluable for efficacy. The most serious adverse effect was thrombocytopenia, which occurred in 12 of 19 patients treated for ten days or more. Serious bleeding associated with thrombocytopenia was observed in two patients. Other common adverse effects were anorexia, nausea, and diarrhea. Prior to receiving eflornithine, 13 of 15 responders had received ten or more days of conventional therapy without demonstrating clinical improvement. Two had improved while receiving conventional therapy but were switched to eflornithine because of a treatment-limiting adverse effect of standard therapy. These results suggest that eflornithine may be useful as an alternative therapeutic agent for Pneumocystis carinii pneumonia. Studies designed to determine proper dosage, duration of therapy, and efficacy as primary therapy are warranted.

Severe infections treated with intravenous ofloxacin: a prospective clinical multicentre Swiss study

In this open prospective clinical trial of iv ofloxacin, 87 patients were treated for severe bacterial infections. Overall results showed a clinical cure rate of 75% and 79/87 87 patients improved. 86% of causative organisms (all sensitive to ofloxacin) were eliminated. The best results were obtained in urinary tract infections where all 30 patients were clinically cured and 27 organisms (Escherichia coli, group D streptococcus, Proteus mirabilis and Klebsiella pneumoniae) were eliminated. Rapid clinical cure was observed in five patients with prostatitis. Good results were seen in arthritis and osteomyelitis. Less than three days of parenteral therapy were required before improvement was seen in patients presenting with severe enterocolitis. Ofloxacin treatment was used for the treatment of lower respiratory tract infections in 35 patients. Clinical improvement was noted in 28 patients. Five patients had unsatisfactory responses, mainly due to underlying diseases. There were two failures, both in pneumococcal pneumonia. Three minor side effects were recorded. Ofloxacin can be given for severe bacterial infections due to Enterobacteriaceae, other Gram-negative rods and other sensitive organisms. It can be given in penicillin allergic patients but it should not be used in pneumococcal pneumonia.

Multicenter, randomized trial of ciprofloxacin plus azlocillin versus ceftrazidime plus amikacin for empiric treatment of febrile neutropenic patients

In a multicenter, randomized clinical trial, the efficacy of ciprofloxacin plus azlocillin was compared with that of a standard regiment of cerftazidime plus amikacin for the initial empiric treatment of fever in neutropenic cancer patients. In addition, the efficacy of early conversin from intravenous therapy to orally administered ciprofloxacin was compared with that of continued ceftrazidime plus amikacin. Seventy-one oncology patients with 79 episodes of fever and neutropenia were randomly assigned to receive initial empiric antibiotic therapy with either intravenously administered ciprofloxacin and azlocillin followed by orally administered ciprofloxacin (regimen 1, 25 episodes); ceftazidime and amikacin (regimen 2, 30 episodes), or ceftazidime and amikacin followed by oral ciprofloxacin (regimen 3, 24 episodes). Microbiologically documented infections were the cause of fever in 10 (40 percent), seven (23 percent), and nine (38 percent) episodes in regimens 1,2 and 3, respectively, including six, five, and four episodes of bacteremia. Patient survival was 90 to 92 percent in each regimen; however, some modification of antimicrobial therapy occurred in 65, 44 and 41 percent of surviving patients in regimens 1,2, and 3, respectively. The rate of clearance of initial bacteremia was 67 percent (four of six) in regimen 1, 100 percent (five of five) in regimen 2 and 50 percent (two of four) in regimen 3. Patients in regimens 1 and 3 were able to convert to orally administered ciprofloxacin in 32 (65 percent) of 49 episodes after a mean of six days of intravenous therapy. Superinfections occurred in 24, 10, and 12 percent of patients receiving regimens 1,2 and 3, respectively, and occurred similarly for patients receiving orally administered ciprofloxacin, 12 percent (four of 32), and intravenous therapy, 17 percent (eight of 47). Parenteral ciprofloxacin was generally well tolerated. One (4 percent) of 25 patients receiving regimen 1 experienced oto- or nephrotoxicity, compared with eight (15 percent) of 54 patients receiving regimens 1,2 and 3 (p = 0.15), including three patients who required premature termination of aminoglycosides therapy. Our data suggest that the combination of ciprofloxacin and azlocillin is an effective alternative to ceftazidime and amikacin for the initial empiric therapy of febrile neutropenic patients, is generally well tolerated, and avoids the oto- and nephrotoxicity associated with aminoglycoside use. In addition, a majority of patients could change to orally administered ciprofloxacin alone after sic days of parenteral therapy.

Effects of methotrexate on intestinal transit in rats

A study was designed to determine the effects of methotrexate (MTX) on rat intestinal transit. Adult male rats were implanted with indwelling cannulas in the proximal duodenum 5 to 7 days prior to experimentation. After recovery from surgery, groups of animals were treated with either saline (1.0 ml/kg/day) or MTX at 0.5, 1.25, 3.125, or 7.8 mg/kg/day (ip) for 3 consecutive days (Days 1–3). On each of the next 5 consecutive days (Days 4–8) weight and intestinal transit determinations were made in animals from each test group following a 24-hr fast. Intestinal transit was determined by measuring the progression of an intraduodenally administered bolus of radioactive chromium (Na 2 51CrO 4, 0.5 μCi) through the small intestine. When compared with saline-treated controls, intestinal transit was significantly ( p < 0.05) increased on 1 or more of the 5 test days in animals treated with doses of MTX greater than 0.5 mg/kg/day. When compared with animals treated with saline, animals treated with MTX lost a greater percentage of their initial body weight after the fast period. Plasma concentrations of MTX, determined at various time intervals after 3.125 mg/kg given daily for 1 to 3 consecutive days, peaked at 15 and 30 min after each injection and diminished to undetectable levels after 4 hr. The results indicate that 3 days of parenteral therapy with MTX significantly increases rat intestinal transit. The intestinal effects appear to be transient and are proportional to the total dose of drug administered over the 3-day period. The intestinal effects of MTX occur from 1 to several days after peak plasma concentrations of drug and are associated with a reduced ability to sustain body weight after a 24-hr fast.