[A case of recurrent Campylobacter fetus meningitis, occurring two months after the |initial infection was successfully treated].

A 43-year-old man was admitted to our department due to fever and headache. The cerebrospinal fluid analysis confirmed bacterial meningitis. Campylobacter species were isolated from blood cultures on the third day of admission. The patient was treated with meropenem (MEPM) and discharged on the 17th day. However, he experienced a recurrence of meningitis and was readmitted on the 68th day, initiating MEPM therapy. Campylobacter fetus was isolated from cerebrospinal fluid cultures on the 74th day. MEPM was continued until the 81st day, followed by one month of minocycline (MINO) therapy. The patient had an uneventful recovery without further recurrence. This case highlights the potential for recurrence of Campylobacter fetus meningitis approximately two months after the resolution of the initial infection. In addition to carbapenem therapy for at least two weeks, the adjunctive administration of MINO may be beneficial.

[The overlap Stevens-Johnson syndrome due to meropenem administration. Clinical case and nursing care]. / Sindrome da overlap di Stevens-Johnson causata dalla somministrazione di meropenem. Descrizione clinica e trattamento infermieristico.

. The overlap Stevens-Johnson syndrome due to meropenem administration. Clinical case and nursing care. A case of overlap Stevens-Johnson syndrome caused by meropenem administration is described. It is a rare cutaneous reaction due to delayed hypersensitivity to drugs characterised by the destruction and separation of the skin epithelium and mucous membranes, affecting between 10% and 29% of the body surface area. The clinical description of the case and a detailed description of nursing management and interventions based on the available literature are reported.

Meropenem-vaborbactam for the treatment of complicated urinary tract infections including acute pyelonephritis.

INTRODUCTION: Meropenem-vaborbactam is a new beta-lactam/beta-lactamase inhibitor combination that combines a carbapenem antibiotic with a first-in-class, boronic acid pharmacophore, serine beta-lactamase inhibitor which has potent inhibitory activity against class A carbapenemases, especially Klebsiella pneumoniae carbapenemases (KPC), in addition to other class A and class C beta-lactamases. The US Food and Drug Administration has recently approved meropenem-vaborbactam for the treatment of adult patients with complicated urinary tract infections including acute pyelonephritis. Areas covered: A PubMed search was performed to gather the most current and relevant articles regarding meropenem-vaborbactam. In this review the authors discuss the chemistry, mechanism of action, pharmacokinetics, pharmacodynamics, antimicrobial spectrum, and efficacy and safety of meropenem-vaborbactam for the treatment of complicated urinary tract infections including acute pyelonephritis Expert opinion: Although meropenem-vaborbactam is approved for treatment for complicated urinary tract infections including acute pyelonephritis, it is unlikely, at this point, to be utilized widely beyond cases that are caused by KPC-producing Enterobacteriaceae. It may also be a potential treatment option for complicated urinary tract infections caused by KPC-producing Enterobacteriaceae that are resistant to ceftazidime-avibactam. Long-term safety data with this novel beta-lactamase inhibitor is still needed although early data suggests that it will be safe and well tolerated.

Pharmacokinetic evaluation of meropenem and vaborbactam for the treatment of urinary tract infection.

INTRODUCTION: Meropenem/vaborbactam (M/V) represents the first carbapenem and ß-lactamase inhibitor combination approved for treatment of complicated urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a novel boronic acid, ß-lactamase inhibitor with a high affinity for serine ß-lactamases, including Klebsiella pneumoniae carbapenemase (KPC). This combination, Vabomere™, was approved in August 2017 by the United States Food and Drug Administration for the treatment of cUTIs in patients 18 years or older, including pyelonephritis, caused by the following susceptible microorganisms: Escherichia coli, K. pneumoniae, and Enterobacter cloacae species complex. Areas covered: Relevant literature regarding microbiology, pharmacokinetics, pharmacodynamics, and clinical trials evaluating efficacy, safety, and tolerability will be discussed. Expert opinion: Current treatment options for KPC-producing infections such as aminoglycosides, polymyxins, fosfomycin, and tigecycline are associated with concerns regarding efficacy, toxicities, optimal dosing, and/or development of resistance. Additionally, resistance to the new combination product of ceftazidime/avibactam has also emerged. Current clinical evidence supporting the use of M/V for KPC-producing infections is limited to an open-label, randomized, phase III study in a small number of patients with serious infections due to carbapenem-resistant Enterobacteriaceae. Although M/V is not approved for KPC-producing infections, we believe that M/V will become a preferred agent for KPC-producing Enterobacteriaceae infections.

Composite particle formulations of colistin and meropenem with improved in-vitro bacterial killing and aerosolization for inhalation.

Antibiotic combination therapy is promising for the treatment of lower respiratory tract infections caused by multi-drug resistant Gram-negative pathogens. Inhaled antibiotic therapy offers the advantage of direct delivery of the drugs to the site of infection, as compared to the parenteral administrations. In this study, we developed composite particle formulations of colistin and meropenem. The formulations were characterized for particle size, morphology, specific surface area, surface chemical composition, in-vitro aerosolization performance and in-vitro antibacterial activity. The combinations demonstrated enhanced antibacterial activity against clinical isolates of Acinetobacter baumannii N16870 and Pseudomonas aeruginosa 19147, when compared with antibiotic monotherapy. Spray-dried meropenem alone showed a poor aerosolization performance as indicated by a low fine particle fraction (FPF) of 32.5 ±â€¯3.3%. Co-spraying with colistin improved the aerosolization of meropenem with up to a two-fold increase in the FPF. Such improvements in aerosolization can be attributed to the enrichment of colistin on the surface of composite particles as indicated by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), and the increases in particle porosity. Intermolecular interactions between colistin and meropenem were observed for the combination formulations as measured by FT-IR. In conclusion, our results show that co-spray drying with colistin improves the antibacterial activity and aerosol performance of meropenem and produces a formulation with synergistic bacterial killing.

The successful treatment of a multidrug-resistant Achromobacter xylosoxidans corneal ulcer with topical meropenem.

Microbial keratitis is a common corneal condition, with many known risk factors. We present a case of an 88-year-old female patient with a multidrug-resistant Achromobacter xylosoxidans corneal ulcer in a previously failed second penetrating keratoplasty, successfully managed with topical meropenem drops administered hourly around the clock, for five days preceding and then hourly day only, for five days following a repeat third penetrating keratoplasty. Topical meropenem 50 mg/mL was prepared by mixing a 500 mg vial of meropenem with 10 mL of sterile water with pharmacy advice that administration should be within an hour. To the best of our knowledge, this is the first report of the use of topical meropenem in the management of A.xylosoxidans keratitis. This case highlights the importance of the mean inhibitory concentrations for antibiotics when considering sensitivities. Topical meropenem may be a useful treatment option for multidrug-resistant bacterial corneal ulcers that are resistant to conventional therapy.

Conservative management of acute calculous cholecystitis complicated by pancreatitis in an elderly woman: A case report.

RATIONALE: Acute calculous cholecystitis is a prevalent disease whose diagnosis and management still face significant debate. Although the overall incidence of gallstone disease is 18.8% in European women aged 30 to 69 years, there is little data and experience in managing acute calculous cholecystitis in populations over 80 years old. The incidence of acute cholecystitis among the elderly is probably increasing. For the reason, we here highlight the advantages and disadvantage of various treatment and management opens based on a 96-year-old patient. PATIENT CONCERNS: We present a rare case in which a 96-year-old woman suffered from abdominal pain, nausea, and lack of appetite for over a month. DIAGNOSES: She was diagnosed with acute calculous cholecystitis and pancreatitis. INTERVENTIONS: She was successfully treated without surgery, regaining her physical health after 5 months. OUTCOMES: The question of how to manage acute calculous cholecystitis is extremely difficult in many aspects. The patient of very advanced age presented in this paper, not very well diagnosed and with a life-threating condition, survived because of careful treatment and reasonable decision-making. LESSONS: The take-away from this case is that, in a high-risk senile patient, strict conservative therapy of cholecystitis may be successful, as it can avoid the complications of surgery and leave the patient with a good quality of life.

Clinical features and outcome of patients with cutaneous melioidosis during a nosocomial outbreak in a temperate region of Australia.

Six cases of cutaneous melioidosis from southwestern Australia, a non-endemic region occurred as a result of Burkholderia pseudomallei contamination of normal saline that was used for irrigating superficial wounds. Treatment with parenteral meropenem, given by continuous infusion for 2 weeks, followed by oral antibiotics was successful in all cases.

A successful treatment of necrotizing fasciitis following the surgery of distal radius plate removal: A case report and literature review.

RATIONALE: Necrotizing fasciitis (NF) is defined as a rare, rapidly progressive, and highly lethal skin infection characterized by necrosis of the fascia and subcutaneous tissue. PATIENT CONCERNS: The present study aims to discuss the case of a 35-year-old man who developed NF following a routine sterile right distal radius bone plate removal surgery. DIAGNOSES: The patient was suspected of NF based on his clinical manifestations, laboratory tests, and imaging results. The diagnosis of NF was confirmed by histological examinations. INTERVENTIONS: Serial prompt and extensive debridement was performed during the rapid and aggressive extension of the skin infection, together with antibiotics and supportive treatments. OUTCOMES: The condition of the patient finally improved on the sixth day of disease progression. Skin grafting of his right forearm wound was performed successfully 2 months after the admission. LESSONS: NF can occur during the perioperative period for routine clean radius plate removal operation in patients with no risk factor for NF. The objective is to remind the physicians to stay aware of this disease, especially its early clinical signs and symptoms. Urgent subsequent treatment, including surgical debridement, antibiotic therapy, and supporting management, is the key to ensure the survival and better prognosis of patients.

Meropenem time above the MIC exposure is predictive of response in cystic fibrosis children with acute pulmonary exacerbations.

Meropenem exposures from 15 children (8-17 years old) with cystic fibrosis (CF) acute pulmonary exacerbation were analyzed to define the pharmacodynamic threshold required for a positive response. The primary endpoint was the relative increase in forced expiratory volume in 1 s (↑FEV1) between pre- and posttreatment. Meropenem pharmacodynamic indices (fT > MIC, fAUC/MIC, fCmin/MIC) over the first 24 h were estimated for each participant based on their individual parameter estimates and the isolated pathogen with the highest meropenem MIC. Pseudomonas aeruginosa was the most common pathogen (n = 11/15). The mean ± SD ↑FEV1 was 18.8% ± 11.3% posttreatment. The mean (range) fT > MIC exposure was 63% (0-100%). An Emax model determined a significant relationship between fT > MIC and ↑FEV1 (r2 = 0.8, P < 0.0004). 65% fT > MIC was a significant predictor of response; the median (25th, 75th %) ↑FEV1 was 28.5% (22.2%, 31.7%) in those patients who achieved above 65% fT > MIC and 7.8% (1.1%, 12.6%) in those at or below 65% fT > MIC (P = 0.001). This is the first study in CF children to link meropenem exposure with a positive response as measured by ↑FEV1. Larger studies are required to confirm this exposure threshold.

Sphingomonas paucimobilis empyema caused by remote foreign body aspiration.

Empyema secondary to foreign body aspiration is rare in adults. We present a case of empyema in a 77-year-old male patient related to a remote aspiration event during a dental procedure. A CT of the chest and bronchoscopy confirmed that a metallic foreign body was located within the right lower lobe bronchus. His pleural fluid culture revealed Sphingomonas paucimobilis which is a low-virulent opportunistic gram-negative bacilli and rarely causes infection. The patient received meropenem followed by levofloxacin and recovered uneventfully. The attempt of foreign body removal was failed due to chronic inflammation, and the patient refused further surgical management.

Effect of Meropenem-Vaborbactam vs Piperacillin-Tazobactam on Clinical Cure or Improvement and Microbial Eradication in Complicated Urinary Tract Infection: The TANGO I Randomized Clinical Trial.

Importance: Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections. Objective: To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis. Design, Setting, and Participants: Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region. Interventions: Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment. Main Outcomes and Measures: Primary end point for FDA criteria was overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-to-treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was -15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95% CIs were calculated. Results: Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%] women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-tazobactam (difference, 4.5% [95% CI, 0.7% to 9.1%]; P < .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenem-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference, 9.0% [95% CI, -0.9% to 18.7%]; P < .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9% [95% CI, -4.2% to 16.0%]; P < .001 for noninferiority). Adverse events were reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-tazobactam. Conclusions and Relevance: Among patients with complicated UTI, including acute pyelonephritis and growth of a baseline pathogen, meropenem-vaborbactam vs piperacillin-tazobactam resulted in a composite outcome of complete resolution or improvement of symptoms along with microbial eradication that met the noninferiority criterion. Further research is needed to understand the spectrum of patients in whom meropenem-vaborbactam offers a clinical advantage. Trial Registration: clinicaltrials.gov Identifier: NCT02166476.

Emphysematous endocarditis caused by AmpC beta-lactamase-producing Escherichia coli: A case report.

RATIONALE: Infective endocarditis (IE) is a life-threatening disease, mostly caused by gram-positive bacteria. Gram-negative bacteria were identified as a causative organism in relatively small number of cases. Although, antibiotic-resistant Escherichia coli is common cause of gram-negative endocarditis, AmpC beta-lactamase (BL)-harboring E coli is very rare cause of IE. Furthermore, emphysematous endocarditis is also a very rare manifestation of E coli infection. PATIENT CONCERNS: We report a case of 80-year-old female patient presenting with dizziness, fever, and altered mental status, who was finally diagnosed with emphysematous endocarditis caused by E coli harboring an AmpC BL gene. DIAGNOSIS: Her chest computed tomography revealed air bubbles surrounding the annulus of a mitral valve and a transesophageal echocardiogram revealed a hyperechogenic mass fixed on the posteromedial side of the mitral annulus with 2 eccentric mitral regurgitation jets. Blood cultures grew E coli which harbored the DHA-type AmpC BL. The organism belonged to a B2 phylogenic group, and multilocus sequence typing analyses revealed that the strains were of ST-95. INTERVENTIONS: She was treated with meropenem following the resistant profiles, and surgery was recommended by the healthcare professional, but denied by the patient's guardians. She was transferred to another hospital due to a refusal for further treatment. LESSONS: Emphysematous endocarditis is an uncommon complication of E coli bacteremia. Certain phylogenetic groups may be associated with development of E coli endocarditis.

Pharmacokinetics of high-dose extended-infusion meropenem during pulmonary exacerbation in adult cystic fibrosis patients: a case series.

This case series explored the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of meropenem (MEM) in adult cystic fibrosis (CF) patients hospitalized for a pulmonary exacerbation. From January 2015 to June 2016, all adult patients with cystic fibrosis (CF) and chronic pulmonary infection due to meropenem (MEM)-susceptible/intermediate Pseudomonas aeruginosa who received at least 48 h of MEM as an extended 3-hour infusion for treating a pulmonary exacerbation were enrolled. MEM plasma concentrations were determined by high-performance liquid chromatography. Six adult CF patients with a median age of 47 years were included in the study. MEM showed a high Vd (mean 45.98 L, standard deviation [SD] ±34.45). A minimal PK/PD target of 40% T > minimum inhibitory concentration (MIC) with respect to the MEM MIC of P. aeruginosa strains isolated from sputum during exacerbation was achieved in 5/6 patients (83%). MEM failed to achieve this target only in one patient, whose strain showed the highest MEM MIC in our cohort (8 mg/L). In all patients, MEM was well tolerated, and no adverse events were reported. In conclusion, high-dose, extended-infusion MEM during pulmonary exacerbation showed a high Vd in six adult CF patients with high median age, and was well tolerated.

A case of liver abscess co-infected with Desulfovibrio desulfuricans and Escherichia coli and review of the literature.

A 73-year-old woman was admitted with consciousness disturbance following a fever. Abdominal computed tomography revealed a large liver abscess with which the presence of Desulfovibrio desulfuricans and Escherichia coli was confirmed by thorough blood and abscess content culture. Empiric meropenem treatment was switched to cefoperazone/sulbactam, followed by ampicillin/sulbactam based on susceptibility testing. Desulfovibrio desulfuricans is a common bacterium that rarely causes liver abscess and may be overlooked during co-infection due to overgrowth of the accompanying bacteria. Clinicians should bear Desulfovibrio desulfuricans in mind and select the appropriate antibiotics according to susceptibility testing when anaerobic bacteria are detected in a liver abscess.

Retrospective evaluation of piperacillin-tazobactam, imipenem-cilastatin and meropenem used on surgical floors at a tertiary care hospital in Saudi Arabia.

BACKGROUND: The appropriate use of broad-spectrum antibiotics, including appropriate de-escalation, is essential to reduce the emergence of antibiotic resistance. In surgical floors antibiotics are prescribed for prophylaxis (mostly, single dose), empirical treatment (started if infection is suspected till bacteria are identified with its sensitivity to antibiotics), or treatment of well-defined infection of previously isolated bacteria with its sensitivity to antibiotics. In this study, we aimed to evaluate the use of broad-spectrum antibiotics based on requests for cultures and de-escalation based on sensitivity results of culture tests at tertiary care hospital. METHOD: A retrospective cohort study was conducted to evaluate the utilization of broad-spectrum antibiotics on surgical floors at a tertiary care center in Jeddah, Saudi Arabia. Patients who are admitted to surgical floors were included if they received any of three broad-spectrum antibiotics (piperacillin-tazobactam, imipenem-cilastatin or meropenem) from 1 June 2014 to 31 August 2014. Data were collected on whether culture and sensitivity test requests were made within 24h of starting antibiotics, the duration of antibiotic therapy and the number of days to de-escalation after receiving culture and sensitivity results. RESULTS: Of the 163 patients who received broad-spectrum antibiotics, culture tests were requested in 112. Before receiving culture results, one patient was discharged and one died. The results of culture tests justified continuation of broad-spectrum antibiotics in only 22 patients, whereas 24 showed no microbial growth in any culture. De-escalation was delayed >24h after culture results became available in 33 out of 64 eligible patients. On the other hand, 51 patients continued receiving broad spectrum antibiotics without any culture test during the whole treatment course. CONCLUSION: The use of broad-spectrum antibiotics in surgical floors at a tertiary care hospital in Saudi Arabia was largely unjustified by culture-test result. Interventions are needed to enforce culture and sensitivity test requests within 24h of starting the broad spectrum antibiotics therapy with further follow up to ensure appropriate de-escalation and discontinuation whenever indicated.

Dosing optimization of meropenem based on a pharmacokinetic analysis in patients receiving hemodiafiltration and an in vitro model.

The purpose of this study was to estimate the in vivo pharmacokinetics of meropenem during intermittent-infusion hemodiafiltration (I-HDF) and clarify its optimal dosage and dosing interval in patients receiving I-HDF. The clearance of meropenem by online hemodiafiltration (OL-HDF) and I-HDF was predicted using an in vitro system and assessed to establish whether the results obtained are applicable to clinical cases. In the in vivo study, the mean volume of distribution (Vd), non-I-HDF clearance (CLnon-I-HDF), and I-HDF clearance (CLI-HDF) were 15.80 ± 3.59 l, 1.05 ± 0.27 l/h, and 5.78 ± 1.03 l/h. Dosing regimens of 0.25 g once daily for a MIC of 8 µg/ml and of 0.5 g once daily for a MIC of 16 µg/ml achieved 40% T > MIC. In the in vitro and in vivo studies, observed CLHDF was similar to predictive CLHDF (= Cf/Cp × (QD + QSUB)). In conclusion, adjustments to the dose and interval of meropenem were developed based on the presumed susceptibility of pathogens to meropenem in patients receiving I-HDF. We suggest 0.5 g once daily as an appropriate regimen for empirical treatment.

Maximally effective dosing regimens of meropenem in patients with septic shock.

OBJECTIVES: To use a population pharmacokinetic approach to define maximally effective meropenem dosing recommendations for treatment of Acinetobacter baumannii and Pseudomonas aeruginosa infections in a large cohort of patients with septic shock. METHODS: Adult patients with septic shock and conserved renal function, treated with meropenem, were eligible for inclusion. Seven blood samples were collected during a single dosing interval and meropenem concentrations were measured by a validated HPLC-MS/MS method. Monte Carlo simulations were employed to define optimum dosing regimens for treatment of empirical or targeted therapy of A. baumannii and P. aeruginosa. EudraCT-no. 2014-002555-26 and NCT02240277. RESULTS: Fifty patients were included, 26 male and 24 female, with a median age of 64 years with an all-cause 90 day mortality of 34%. A two-compartment linear model including creatinine clearance (CLCR) as a covariate best described meropenem pharmacokinetics. For empirical treatment of A. baumannii, 2000 mg/6 h was required by intermittent (30 min) or prolonged (3 h) infusion, whereas 6000 mg/day was required with continuous infusion. For P. aeruginosa, 2000 mg/8 h or 1000 mg/6 h was required for both empirical and targeted treatment. In patients with a CLCR of ≤ 100 mL/min, successful concentration targets could be reached with intermittent dosing of 1000 mg/8 h. CONCLUSIONS: In patients with septic shock and possible augmented renal clearance, doses should be increased and/or administration should be performed by prolonged or continuous infusion to increase the likelihood of achieving therapeutic drug concentrations. In patients with normal renal function, however, standard dosing seems to be sufficient.

Meropenem versus piperacillin/tazobactam with or without immunoglobulin as second-line therapy for febrile neutropenia in pediatric patients.

BACKGROUND: Although survival of children with hematological diseases and cancer has increased dramatically, life-threatening complications due to bacterial infections occur in 5-10% of febrile episodes in pediatric cancer patients. A prospective randomized study was performed to clarify the usefulness of meropenem (MEPM) and piperacillin/tazobactam (PIPC/TAZ) with or without intravenous immunoglobulin (IVIG) as second-line therapy for pediatric patients with febrile neutropenia (FN). PROCEDURE: As first-line therapy for FN, 105 patients with 434 episodes were randomly assigned to receive MEPM or PIPC/TAZ. A total of 71 pediatric patients and 144 episodes were judged as failures and enrolled for second-line treatment. In second-line treatment, patients were randomized to a group of MEPM and PIPC/TAZ with or without IVIG. MEPM was given to patients who received PIPC/TAZ as first-line treatment, and PIPC/TAZ was given to patients who received MEPM as first-line treatment. RESULTS: The total success rate of second-line therapy was 49.3%. MEPM with or without IVIG was effective in 44.3% of cases, and PIPC/TAZ with or without IVIG was effective in 55.3%; this difference was not significant. The success rate in patients with serum IgG under 1000 mg/dl was 41.3% in the MEPM or PIPC/TAZ group and 64.3% in the MEPM + IVIG or PIPC/TAZ + IVIG group (p = 0.028). CONCLUSIONS: The present results suggest that PIPC/TAZ is as effective as MEPM and safe for second-line treatment of FN in pediatric patients. Furthermore, IVIG appears very effective for patients with low serum IgG levels.

Evaluating biapenem dosage regimens in intensive care unit patients with Pseudomonas aeruginosa infections: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

This study was conducted to identify optimal dosage regimens and estimate pharmacokinetic/pharmacodynamic (PK/PD) characteristics of short-infusion (SI) versus extended-infusion (EI) biapenem against Pseudomonas aeruginosa infections in Chinese intensive care unit (ICU) patients. A total of 85 strains of P. aeruginosa were collected, and the minimum inhibitory concentration (MIC) of biapenem was measured by the serial two-fold agar dilution method. We designed four frequently used clinical regimens: biapenem 300 mg I.V. q12h, q8h, and q6h, and 600 mg q12h. The Monte Carlo Simulation (MCS) was performed using previously published pharmacokinetic data to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of these regimens as an SI (0.5 h) and an EI (1 h, 2 h, 3 h, and 4 h). For a target of 40%fT>MIC (serum drug concentration remains above the MIC for a dosing period), none of the regimens achieved any CFRs>90% for P. aeruginosa, multidrug-resistant P. aeruginosa (MDR-PA) and even non-MDR-PA. The traditional biapenem SI regimens most commonly seen in clinical practice were insufficient in treating both MDR and non-MDR P. aeruginosa in ICU patients. However, biapenem 600 mg q12h over 2-4 h EI regimens could achieve CFR>90% with 20%fT>MIC. Clinical trials should aim to validate the potentially greater PK/PD index with higher, more frequent doses and longer extended infusions.