Antibiotic Consumption 2017-2022 in 30 Private Hospitals in France: Impact of Antimicrobial Stewardship Tools and COVID-19 Pandemic.

Our aim was to determine the impact of antimicrobial stewardship tools (ASTs) and the COVID-19 pandemic on antibiotic consumption (AC). We used the national software Consores® to determine AC in DDD/1000 days of hospitalization from 2017 to 2022 in voluntary private hospitals in France. The ASTs considered were: 1. internal guidelines; 2. the list of antibiotics with restricted access; 3. the presence of an antibiotic referent or 4. an ID specialist; and 5. proof of an annual meeting on antimicrobial resistance. Institutions with dedicated units for COVID-19 patients were specified. In 30 institutions, the total AC varied from (means) 390 to 405 DDD/1000 DH from 2017 to 2022. Fluoroquinolones and amoxicillin/clavulanate consumption decreased from 50 to 36 (p = 0.003) and from 112 to 77 (p = 0.025), respectively, but consumption of piperacillin/tazobactam increased from 9 to 21 (p < 0.001). Over the study period, 10 institutions with ≤2 AST had lower AC compared to 20 institutions with ≥3 AST (p < 0.01). COVID-19 units opened in 10 institutions were associated with a trend toward higher macrolide consumption from 15 to 25 from 2017 to 2020 (p = 0.065) and with an acceleration of piperacillin/tazobactam consumption from 2020 to 2022 (p ≤ 0.003). Antibiotic consumption in 30 private hospitals in France was inversely related to the number of AST. The COVID-19 pandemic was associated with limited impact on AC, but special attention should be paid to piperacillin/tazobactam consumption.

Prosthetic joint infections: 6 weeks of oral antibiotics results in a low failure rate.

BACKGROUND: Need for parenteral administration and total duration of antibiotic therapy for prosthetic joint infection (PJI) are debated. We report our PJI management, in which outpatient care is privileged. METHODS: This was a retrospective multicentre cohort study of PJI managed from January 2017 to Jun 2021. Microbial diagnosis was based on surgical samples. Surgical procedures and antibiotic treatments were reported. Chronic PJI was defined by a course >1 month. Oral antibiotic therapy (OAT) was defined by exclusive use of oral antibiotics or by ≤3 days of parenteral treatments. Management failure was defined by clinical and/or microbial relapse of PJI over 24 months after surgical treatment. RESULTS: One hundred and seventy-two patients from 13 institutions were included: 103 were male (60%) and mean age was (±SD): 73 ±â€Š12 years. Sites for PJI were mainly hip (50%) and knee (35%), being chronic infections in 70 cases (41%). The main bacterial genus in monomicrobial infections was Staphylococcus spp. (60%). We recorded 41 (24%) implant exchanges. An OAT was prescribed in 76 cases (44%), and the median (range) course for parenteral route was 6 days (4-180) for 96 cases. Median (range) duration of antimicrobials was 42 days (21-180). Management failure was observed in 7/76 (9.2%) cases treated with OAT and 15/96 (15.6%) treated with prolonged parenteral therapy. In multivariate analysis, risk factors for failure were a knee PJI [adjusted OR (95% CI) = 3.27 (1.27-8.40)] and a polymicrobial infection [4.09 (1.46-11.49)]. CONCLUSIONS: OAT for 6 weeks for PJI was associated with a low rate of management failure.

Simplified antibiotic guidelines in urology are associated with decreased multidrug-resistant Enterobacterales.

PURPOSE: A simplified therapeutic guideline (STG) was established in our urology ward in 2019 for urinary infections. Our aim was to describe the level of physician adherence to STG and the impact of a limited number of antibiotic compounds on the rate of multidrug-resistant (MDR) bacteria. As guidelines should improve patient care, unfavorable outcomes were also reported. METHODS: The STG for community-acquired and nosocomial urinary infections, including six antibiotics, was established in November 2019 and has been officially applied since January 2020. Treatment duration has to be ≤14 days. We conducted a before-after study to measure physician adherence to the STG for bacteremia treatment between January 2017 and December 2022. Adherence was defined as exclusive use of STG antibiotics. All isolated bacteria from blood cultures were recorded, including MDR Enterobacterales, defined as AmpC ß-lactamase- or ESBL-producing strains. Unfavorable outcomes were defined as uncontrolled infection, a second surgical procedure, ICU requirement, and/or death. RESULTS: Seventy-six cases of bacteremia occurred between January 2017 and December 2019, and ninety between January 2020 and December 2022. The main comorbid condition was urological cancer (46%). The main reason for surgery was ureteral stent (32%). Antibiotic management in accordance with STG increased from 18% to 52%, p < 0.001, and treatments > 14 days decreased from 53% to 28%, p < 0.001. MDR Enterobacterales bacteremia was reduced from 52% to 35%, p = 0.027. The rate of unfavorable outcomes was unchanged. CONCLUSION: STG adherence in urology was satisfactory and associated with reduced MDR Enterobacterales bacteremia.

Diagnostic uncertainty in infectious diseases: Advocacy for a nosological framework.

Diagnostic uncertainty (DU) is frequent in infectious diseases (ID), being recorded in 10% to over 50% of patients. Herein, we show that in several fields of clinical practice, high rates of DU are constant over time. DUs are not taken into account in guidelines, as therapeutic propositions are based on an established diagnosis. Moreover, while other guidelines underline the need for rapid broad-spectrum antibiotic therapy for patients with sepsis, many clinical conditions mimic sepsis and lead to unnecessary antibiotic therapy. Considering DU, many studies have been carried out to look for relevant biomarkers of infections, which also attest to non-infectious diseases mimicking infections. Therefore, diagnosis is often primarily a hypothesis, and empirical antibiotic therapy should be reassessed when microbiological data are available. However, other than for urinary tract infections or unexpected primary bacteremia, the high frequency of sterile microbiological samples implies that DU remains central in follow-up, which does not facilitate clinical management or antibiotic optimization. The main way to resolve the therapeutic challenge of DU could be to precisely describe the latter through a consensual definition that would facilitate consideration of DU and its mandatory therapeutic implications. A consensual definition of DU would also clarify responsibility and accountability for physicians in the antimicrobial approval process and l provide an opportunity to instruct their students in this large field of medical practices and to productively conduct relevant research.

Prevalence of post-acute coronavirus disease 2019 symptoms twelve months after hospitalization in participants retained in follow-up: analyses stratified by gender from a large prospective cohort.

OBJECTIVES: Persistent post-acute coronavirus disease 2019 (COVID-19) symptoms (PACSs) have been reported up to 6 months after hospital discharge. Herein we assessed the symptoms that persisted 12 months (M12) after admission for COVID-19 in the longitudinal prospective national French coronavirus disease cohort. METHODS: Hospitalized patients with a confirmed virological diagnosis of COVID-19 were enrolled. Follow-up was planned until M12 after admission. Associations between persistence of ≥3 PACSs at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. RESULTS: We focused on participants enrolled between 24 January 2020 and 15 July 2020, to allow M12 follow-up. The M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to intensive care units during the acute phase. At M12, 27% (194/710) of the participants had ≥3 persistent PACS, mostly fatigue, dyspnoea and joint pain. Among those who had a professional occupation before the acute phase, 91 out of 339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life and Medical Muscle Research Council Scale <57. Compared with men, women more often reported presence of ≥3 persistent PACSs (98/253, 39% vs. 96/457, 21%), depression and anxiety (18/152, 12% vs. 17/268, 6% and 33/156, 21% vs. 26/264, 10%, respectively), impaired physical health-related quality of life (76/141, 54% vs. 120/261, 46%). Women had less often returned to work than men (77/116, 66% vs. 171/223, 77%). CONCLUSIONS: One fourth of the individuals admitted to hospital for COVID-19 still had ≥3 persistent PACSs at M12 post-discharge. Women reported more often ≥3 persistent PACSs, suffered more from anxiety and depression and had less often returned to work than men.

Platelet caspase-1 and Bruton tyrosine kinase activation in patients with COVID-19 is associated with disease severity and reversed in vitro by ibrutinib.

Background: Severity of coronavirus disease 2019 (COVID-19) is often associated with thrombotic complications and cytokine storm leading to intensive are unit (ICU) admission. Platelets are known to be responsible for abnormal hemostasis parameters (thrombocytopenia, raised D-dimers, and prolonged prothrombin time) in other viral infections through the activation of the nucleotide-binding domain leucine repeat rich containing protein 3 inflammasome induced by signaling pathways driven by Bruton tyrosine kinase (BTK) and leading to caspase-1 activation. Objectives: We hypothesized that caspase-1 activation and the phosphorylation of BTK could be associated with the severity of the disease and that ibrutinib, a BTK inhibitor, could inhibit platelet activation. Methods and Results: We studied caspase-1 activation by flow cytometry and the phosphorylation of BTK by Western blot in a cohort of 51 Afro-Carribean patients with COVID-19 disease (19 not treated in ICU and 32 treated in ICU). Patients with a platelet count of 286.7 × 109/L (69-642 × 109/L) were treated by steroids and heparin preventive anticoagulation. Caspase-1 and BTK activation were associated with the severity of the disease and with the procoagulant state of the patients. Furthermore, we showed in vitro that the plasma of ICU patients with COVID-19 was able to increase CD62P expression and caspase-1 activity of healthy platelets and that ibrutinib could prevent it. Conclusions: Our results show that caspase-1 and BTK activation are related to disease severity and suggest the therapeutic hope raised by ibrutinib in the treatment of COVID-19 by reducing the procoagulant state of the patients.

Limited Transmission of Klebsiella pneumoniae among Humans, Animals, and the Environment in a Caribbean Island, Guadeloupe (French West Indies).

Guadeloupe (French West Indies), a Caribbean island, is an ideal place to study the reservoirs of the Klebsiella pneumoniae species complex (KpSC) and identify the routes of transmission between human and nonhuman sources due to its insularity, small population size, and small area. Here, we report an analysis of 590 biological samples, 546 KpSC isolates, and 331 genome sequences collected between January 2018 and May 2019. The KpSC appears to be common whatever the source. Extended-spectrum-ß-lactamase (ESBL)-producing isolates (21.4%) belonged to K. pneumoniae sensu stricto (phylogroup Kp1), and all but one were recovered from the hospital setting. The distribution of species and phylogroups across the different niches was clearly nonrandom, with a distinct separation of Kp1 and Klebsiella variicola (Kp3). The most frequent sequence types (STs) (≥5 isolates) were previously recognized as high-risk multidrug-resistant (MDR) clones, namely, ST17, ST307, ST11, ST147, ST152, and ST45. Only 8 out of the 63 STs (12.7%) associated with human isolates were also found in nonhuman sources. A total of 22 KpSC isolates were defined as hypervirulent: 15 associated with human infections (9.8% of all human isolates), 4 (8.9%) associated with dogs, and 3 (15%) associated with pigs. Most of the human isolates (33.3%) belonged to the globally successful sublineage CG23-I. ST86 was the only clone shared by a human and a nonhuman (dog) source. Our work shows the limited transmission of KpSC isolates between human and nonhuman sources and points to the hospital setting as a cornerstone of the spread of MDR clones and antibiotic resistance genes. IMPORTANCE In this study, we characterized the presence and genomic features of isolates of the Klebsiella pneumoniae species complex (KpSC) from human and nonhuman sources in Guadeloupe (French West Indies) in order to identify the reservoirs and routes of transmission. This is the first study in an island environment, an ideal setting that limits the contribution of external imports. Our data showed the limited transmission of KpSC isolates between the different compartments. In contrast, we identified the hospital setting as the epicenter of antibiotic resistance due to the nosocomial spread of successful multidrug-resistant (MDR) K. pneumoniae clones and antibiotic resistance genes. Ecological barriers and/or limited exposure may restrict spread from the hospital setting to other reservoirs and vice versa. These results highlight the need for control strategies focused on health care centers, using genomic surveillance to limit the spread, particularly of high-risk clones, of this important group of MDR pathogens.

Dedicated team to ambulatory care for patients with COVID-19 requiring oxygen: Low rate of hospital readmission.

OBJECTIVES: We aimed to determine the impact of a dedicated medical team (DMT) on ambulatory care for patients requiring oxygen. METHODS: The DMT selected patients requiring oxygen for less than 5 l/min in the emergency department (ED). The rate of ED readmission was compared in patients managed by the DMT and those managed by the ED physicians (EDPs). Consensual treatment for COVID-19 pneumonia with oxygen requirement was steroids + preventive anticoagulation. RESULTS: A total of 1397 patients with COVID-19 came to our ED from the first to the 31st of August, 2021, among whom 580 (41%) had ambulatory care. A total of 82 (14.1%) patients were managed by the DMT, with a rate of ED readmission of 4.8% (4/82), compared with 13.6% (68/498) for those managed by EDPs (P <0.001). Focusing on the 45/498 (9.0%) patients requiring oxygen and managed by EDPs, the rate of ED readmission was 20%, P = 0.017. Prescription of the consensual treatment concerned 96% versus 40% for those patients requiring oxygen for the DMT and the EDP, respectively (P <0.001). CONCLUSION: A DMT for ambulatory care of patients with COVID-19 requiring oxygen was associated with less return to the ED than usual practices.

Sickle cell disease patients with COVID-19 in Guadeloupe: Surprisingly favorable outcomes.

We investigate risk factors for hospitalization and difference between sickle cell syndromes in a cohort of COVID-19 sickle cell disease (SCD) adult patients managed in the Reference Center of Guadeloupe. We retrospectively collected data of symptomatic SCD adult patients infected with SARS-CoV-2 between March and December 2020. Thirty-eight SCD adult patients with symptomatic COVID-19 infection were included during the first wave, representing 9.6% of the active patient file at our center. The median age (IQR) was 39 years (24-47). Four patients were obese and two had moderate renal failure. The median duration of symptoms (IQR) was 10 days (5-15). Seventeen (44.7%) patients were hospitalized, including two in intensive care unit (ICU) for acute chest syndrome. An 85-year-old SC patient with prostate cancer died. No difference was detected between inpatient and outpatient groups in terms of age, gender, BMI, SCD clinical complications, and in history SCD treatment. There was no difference for severity, hospitalization, length of stay, ICU stay, or death between SS or Sß°-thal patients and SC or Sß+-thal patients. These overall favorable outcomes among symptomatic patients may be related to the low prevalence of comorbidity known to be linked to the more severe forms of COVID-19, but also to the prompt coordinated management of SCD patients in the Reference Center.

Real-world effectiveness of casirivimab plus indevimab in a dedicated ambulatory unit created for patients with early COVID-19 during a massive delta variant wave.

Only limited real-life data are available on the effects of neutralizing monoclonal antibodies in high-risk patients who have early COVID-19 and do not require supplemental oxygen. We prospectively studied 217 patients infected by the delta variant who received casirivimab plus indevimab in a dedicated ambulatory unit created during our 4th COVID wave. Mean age was 64 years, 94% had at least one comorbidity, and mean duration of symptoms was 2.9 days. Oxygen requirement, hospitalization, and mortality rates were 10, 6, and 2.8%, respectively. These results suggest benefits of early administration of neutralizing antibodies in high-risk patients infected with the delta variant.

Use of Antibiotic Prophylaxis for Polymicrobial Urine Culture before Urological Surgery: A Pilot Study.

INTRODUCTION: Preoperative polymicrobial urine cultures are common, but the associated risk of nosocomial infection is currently unknown. We aimed to analyze the risk of postoperative infection in patients with preoperative polymicrobial urine cultures. METHODS: This was a prospective cohort study conducted from November 2018 to October 2020. Polymicrobial urine cultures were defined by at least the presence of 3 bacteria without leukocyturia threshold on two consecutive samples in the month preceding the surgical procedure. Data on postoperative infections were collected during hospitalization until day 30. A postoperative infection was defined by the occurrence of clinical signs (fever, chills, and suppurated process on the surgical site) associated with the prescription of an antibiotic therapy. RESULTS: Sixty-eight patients were included, and seven developed a postoperative infection with a microbe identified in blood or urine cultures. There was a significant association between leukocyturia ≥104 (p = 0.02) and the administration of intraoperative antibiotic prophylaxis (p < 0.001). In contrast, there was no significant association between postoperative infections for patients with polymicrobial preoperative urine cultures and having received or not an empirical antibiotic therapy. CONCLUSION: The rate of postoperative infection in patients with polymicrobial urine culture before urological procedure was 10.2%. Further studies are needed to assess the antibiotic prophylaxis to be used in this situation.

Raltegravir Inclusion Decreases CD4 T-Cells Intra-Cellular Viral Load and Increases CD4 and CD28 Positive T-Cells in Selected HIV Patients.

Raltegravir (RLT) prevents the integration of HIV DNA in the nucleus, but published studies remain controversial, suggesting that it does not decrease proviral DNA. However, there are only a few studies focused on virus-targeted cells. We aimed our study on the impact of RLT inclusion on total intra-cellular viral DNA (TID) in cellular subsets and immune effects in patients with newly acquired undetectable plasmatic viral load (UVL). Six patients having UVL using an antiretroviral combination for 6 months and CD4 T-cells > 350/mL and <500/mL were selected to receive RLT for 3 months from M0 to M3. Patients had 7 sequential viro-immunological determinations from M-1 to M5. Immune phenotypes were determined by flow cytometry and TID quantification was performed using PCR assay on purified cells. TID (median values) at the initiation of RLT in CD4 T-cells was 117 copies/millions of cells, decreased to 27.5 on M3, and remained thereafter permanently under the cut-off (<10 copies/millions of cells) in 4 out of 6 patients. This was associated with an increase of CD4 and CD4 + CD28+ T-cells and a decrease of HLA-DR expression and apoptosis of CD4 T-cells. RLT inclusion led to decreases in the viral load along with positive immune reconstitution, mainly for CD4 T-cells in HIV patients.

Plasma microparticles of intubated COVID-19 patients cause endothelial cell death, neutrophil adhesion and netosis, in a phosphatidylserine-dependent manner.

COVID-19 has compelled scientists to better describe its pathophysiology to find new therapeutic approaches. While risk factors, such as older age, obesity, and diabetes mellitus, suggest a central role of endothelial cells (ECs), autopsies have revealed clots in the pulmonary microvasculature that are rich in neutrophils and DNA traps produced by these cells, called neutrophil extracellular traps (NETs.) Submicron extracellular vesicles, called microparticles (MPs), are described in several diseases as being involved in pro-inflammatory pathways. Therefore, in this study, we analyzed three patient groups: one for which intubation was not necessary, an intubated group, and one group after extubation. In the most severe group, the intubated group, platelet-derived MPs and endothelial cell (EC)-derived MPs exhibited increased concentration and size, when compared to uninfected controls. MPs of intubated COVID-19 patients triggered EC death and overexpression of two adhesion molecules: P-selectin and vascular cell adhesion molecule-1 (VCAM-1). Strikingly, neutrophil adhesion and NET production were increased following incubation with these ECs. Importantly, we also found that preincubation of these COVID-19 MPs with the phosphatidylserine capping endogenous protein, annexin A5, abolished cytotoxicity, P-selectin and VCAM-1 induction, all like increases in neutrophil adhesion and NET release. Taken together, our results reveal that MPs play a key role in COVID-19 pathophysiology and point to a potential therapeutic: annexin A5.

Therapeutic failures of targeted antibiotic prophylaxis in urology.

Targeted antibiotic prophylaxis (TAP) is required for patients with positive urine culture before urological surgery. Our aim was to determine the efficacy of TAP. This was a prospective single-center study performed in a urology department. All patients who underwent a programmed surgery were included. Urine culture was obtained before surgery requiring a prophylaxis: in the case of sterile urines, antibiotics were used in accordance with national recommendations; for positive urine culture, a TAP was used in accordance with susceptibility testing. The drugs were administered for 2 days before surgery until withdrawal of bladder catheter. The occurrence of healthcare-associated infections was registered until day 30 after surgery. Two hundred three patients were included for 8 non-consecutive weeks in 2020, among whom fifteen were lost of sight before day 30. Among the remaining 188 patients, most frequent surgeries were 75 prostatic diseases (40%), 50 endo-ureteral surgeries for JJ stent insertion (27%), and 23 bladder cancers (12%). One hundred forty-eight (79%) patients required a urine culture before procedure; 142/148 (96%) urine cultures were performed, leading to 74 TAP. The main isolated bacteria were 48 Enterobacteriaceae and 8 Enterococcus spp. TAP was cotrimoxazole (n = 30), aminoglycosides (n = 11), amoxicillin (n = 9), fluoroquinolones (n = 7), and others (n = 17). The rate of healthcare-associated infections was 14.8% (11/74), including six microbiologically documented antibiotic failures. The rate of healthcare-associated infection after urological surgery using TAP was high, implying to discuss the choice and the dosage of the antibiotic molecules.

Simplified therapeutic guidelines: the main tool of antimicrobial stewardship programs associated with optimal antibiotic therapy.

Hospitals regularly seek to upgrade their antimicrobial stewardship program (ASP). Our aim was to evaluate the impact of simplified therapeutic guidelines (STGs) compared to various established tools for ASP on the rate of optimal antibiotic therapy (OAT) and antibiotic consumption. Audits of antibiotic prescriptions were carried out over a 24-month period. Feedback information led to STGs (e.g., ≤ 15 drugs). The impact of STGs was based on the rate of OAT, defined as a diagnosis of the infectious disease in the patient's medical records associated with the corresponding therapy indicated in the STGs or in other guidelines. STGs were compared to five other means of ASP: internal or national guidelines, audit, information regarding antibiotic consumption and bacterial resistance, and restricted access to targeted antibiotics. Antibiotic consumption was measured in defined daily doses/1000 days of hospital stay, focusing on third-generation cephalosporins (TGC) and fluoroquinolones (FQ). Twenty-six hospitals were audited from April 2017 to June 2019. A total of 1,028 antibiotic prescriptions were analyzed, including 204 (20%) after STG implementation in seven hospitals. In multivariate analysis, OAT (n = 176, 17%) was associated with STGs, AOR 2.21 [1.51-3.22], and with three tools in place, 1.75 [1.24-2.48]. The relative variations of consumption of TGC and FQ for hospitals with or without STGs were - 13.1 vs. + 9.4% and - 18.5 vs. - 2.7%, respectively, from 2018 to 2019. STGs were more likely than other ASP tools to improve the rate of OAT and to reduce the consumption of antibiotics.

Idiopathic CD4 T Cell Lymphocytopenia: A Case of Overexpression of PD-1/PDL-1 and CTLA-4.

Idiopathic CD4 T cell lymphocytopenia (ICL) is a rare entity characterized by CD4 T cell count of <300 cells/mm3 along with opportunistic infection for which T cell marker expression remains to be fully explored. We report an ICL case for which T lymphocyte phenotype and its costimulatory molecules expression was analyzed both ex vivo and after overnight stimulation through CD3/CD28. The ICL patient was compared to five healthy controls. We observed higher expression of inhibitory molecules PD-1/PDL-1 and CTLA-4 on CD4 T cells and increased regulatory T cells in ICL, along with high activation and low proliferation of CD4 T cells. The alteration in the expression of both the costimulatory pathway and the apoptotic pathway might participate to down-regulate both CD4 T cell functions and numbers observed in ICL.

A Population Pharmacokinetic Analysis of Continuous Infusion of Cloxacillin during Staphylococcus aureus Bone and Joint Infections.

Intravenous administration of antibiotics is recommended during the early phase of methicillin-susceptible S. aureus (MSSA) bone and joint infection (BJI). We sought to compare the plasma concentrations of cloxacillin administered alternately by continuous and intermittent infusion (CI and ItI) in patients with MSSA BJI. In this prospective crossover trial, patients were randomly assigned to receive either 3 days of CI (two 75-mg/kg 12-h cloxacillin infusions per day) and then 3 days of ItI (four 37.5-mg/kg 1-h cloxacillin infusions per day) or vice versa. The drug concentration measurement was performed on day 3 of each type of administration at 1, 6, and 11 h and at 1, 2, 3, 4, and 6 h after the beginning of CI and ItI, respectively. We used the nonparametric algorithm NPAG to estimate population pharmacokinetic (PK) parameters. The final model was used to perform pharmacokinetic/pharmacodynamic (PK/PD) simulations and calculate the probabilities of target attainment (PTA) for several ItI and CI dosing regimens. We considered two PK/PD targets of time spent above the MIC for free cloxacillin concentrations (fT>MIC): 50 and 100%. Eighty-four concentrations from 11 patients were analyzed. A two-compartment model adequately described the data. ItI with q6h regimens and short 1-h infusions of 2,000 or 3,000 mg were associated with low PTA, even for the low target (50% fT>MIC) while 3-h infusions and continuous infusions (6 to 12 g/day) were associated with a PTA of >90% for an MIC up to 0.5 mg/liter. These results support the use of prolonged or continuous infusion of cloxacillin in patients with BJI.