Bifidobacteriaceae Family Diversity in Gut Microbiota of Patients with Renal Failure.

Bifidobacteriaceae family are gut microbiota that exhibit probiotic or health promoting effects on the host. Several studies have suggested that gut microbiota are quantitatively and qualitatively altered in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). The present study aimed to assess the members of Bifidobacteriaceae family in fecal samples of patients with CKD and ESRD and compare them with non-CKD/ESRD patients to find any changes in their counts and diversions in these patients. Twenty fresh fecal samples from patients with CKD/ESRD and twenty from non-CKD/ESRD patients were examined. Whole DNA was extracted from fecal samples and the gut microbiota composition was analyzed by next generation sequencing (NGS). A total of 651 strains were identified from 40 fecal samples, 8 (1.23%) strains of which were identified as family Bifidobacteriaceae. The most abundant species in both control and disease groups were Bifidobacterium adolescentis and Bifidobacterium longum subsp. longum, and the least abundant species in the disease group was Bifidobacterium animalis subsp. lactis. There was no significant difference in the abundance of various species between the disease and control groups (p < 0.05). This study confirms that the members of the Bifidobacteriaceae family are not altered in patients with CKD/ESRD.

Case Report: Renal Failure due to Focal Segmental Glomerulosclerosis in a Patient with Murine Typhus.

Murine typhus is a flea-borne rickettsiosis caused by Rickettsia typhi. When severe, endothelial dysfunction can lead to acute kidney injury secondary to prerenal azotemia or acute tubular necrosis. Here, we describe an unusual cause of kidney injury during the course of murine typhus-focal segmental glomerulosclerosis.

Microbial etiology of pneumonia in patients with decreased renal function.

BACKGROUND: Patients with renal impairment have altered immunity, which might cause vulnerability to specific pathogens and worsen pneumonia-related outcomes. Nonetheless, the microbiological features of pneumonia in patients with decreased renal function remain unknown. METHODS: Therefore, we conducted a retrospective cohort study enrolling adult patients hospitalized with pneumonia to assess this knowledge gap. The baseline estimated glomerular filtration rate (eGFR) and first sputum microbiology during hospitalization were used for statistical analyses. RESULTS: Overall, 1554 patients hospitalized with pneumonia (mean age, 76.1 ± 16.7) were included, and 162 patients had died at the end of hospitalization. The cutoff eGFR value predicting mortality was <55 mL/min/1.73 m2, which defined decreased renal function in this study. Patients with decreased renal function demonstrated a significantly higher risk of fungi and Staphylococcus aureus (S. aureus) infection. On the other hand, this group of patients showed significantly higher neutrophil-to-lymphocyte ratio (NLR), which associated with higher mortality. Additionally, patients with S. aureus had a significantly lower eGFR, lymphocyte count and a higher NLR. CONCLUSIONS: These findings suggested the altered immunity and vulnerability to S. aureus infection in patients with decreased renal function, which may be the underlying cause of worse outcomes of pneumonia in this group of patients.

The aftermath of acute kidney injury: a narrative review of long-term mortality and renal function.

Acute kidney injury (AKI) is a frequent complication of hospitalization and is associated with an increased risk of chronic kidney disease (CKD), end-stage renal disease (ESRD), and mortality. While AKI is a known risk factor for short-term adverse outcomes, more recent data suggest that the risk of mortality and renal dysfunction extends far beyond hospital discharge. However, determining whether this risk applies to all patients who experience an episode of AKI is difficult. The magnitude of this risk seems highly dependent on the presence of comorbid conditions, including cardiovascular disease, hypertension, diabetes mellitus, preexisting CKD, and renal recovery. Furthermore, these comorbidities themselves lead to structural renal damage due to multiple pathophysiological changes, including glomeruloscleroses and tubulointerstitial fibrosis, which can lead to the loss of residual capacity, glomerular hyperfiltration, and continued deterioration of renal function. AKI seems to accelerate this deterioration and increase the risk of death, CDK, and ESRD in most vulnerable patients. Therefore, we strongly advocate adequate hemodynamic monitoring and follow-up in patients susceptible to renal dysfunction. Additionally, other potential renal stressors, including nephrotoxic medications and iodine-containing contrast fluids, should be avoided. Unfortunately, therapeutic interventions are not yet available. Additional research is warranted and should focus on the prevention of AKI, identification of therapeutic targets, and provision of adequate follow-up to those who survive an episode of AKI.

An open-label, randomized, placebo-controlled study on the effectiveness of a novel probiotics administration protocol (ProbiotiCKD) in patients with mild renal insufficiency (stage 3a of CKD).

PURPOSE: Gut dysbiosis has been described in advanced, but not in initial stages of CKD. Considering the relevant impact of gut dysbiosis on renal and cardiovascular risk, its diagnosis and treatment are clinically relevant. METHODS: We designed, open-label, placebo-controlled intervention study (ProbiotiCKD) to evaluate gut microbiota metabolism in a cohort of KDIGO CKD patients (n = 28) at baseline and after a randomly assigned treatment with probiotics or placebo. Gut microbiota status was evaluated on:. RESULTS: Basal mean fecal Lactobacillales and Bifidobacteria concentrations were abnormally low in both groups, while urinary indican and 3-MI levels were, indicating a mixed (fermentative and putrefactive) dysbiosis. After treatment, mean fecal Lactobacillales and Bifidobacteria concentrations were increased, only in the probiotics group (p < 0.001). Conversely, mean urinary indican and 3-MI levels only in the group treated with probiotics (p < 0.001). Compared to placebo group, significant improvements of C-reactive protein (p < 0.001), iron (p < 0.001), ferritin (p < 0.001), transferrin saturation (p < 0.001), ß2-microglobulin (p < 0.001), serum iPTH and serum calcium were observed only in the probiotics group. CONCLUSIONS: ProbiotiCKD is the first intervention study demonstrating that an intestinal mixed dysbiosis is present even in early CKD stage and can be effectively corrected by the novel mode of administration of high-quality probiotics with improvement of inflammatory indices, iron status and iPTH stabilization.

Ureaplasma urealyticum pyelonephritis presenting with progressive dysuria, renal failure, and neurologic symptoms in an immunocompromised patient.

Ureaplasma urealyticum is a bacterial species correlated with urethritis in healthy individuals and invasive infections in immunocompromised patients. We describe a 20-year-old female with a history of remote heart transplant on everolimus, mycophenolate, and rituximab presenting with progressive urinary tract symptoms, renal failure, and neurologic symptoms. An extensive workup ultimately identified U urealyticum infection, and the patient successfully recovered after a course of azithromycin and doxycycline.

A Phase 1 Study To Assess the Pharmacokinetics of Intravenous Plazomicin in Adult Subjects with Varying Degrees of Renal Function.

Plazomicin is an FDA-approved aminoglycoside for the treatment of complicated urinary tract infections. In this open-label study, 24 adults with normal renal function or mild, moderate, or severe renal impairment (n = 6 per group) received a single 7.5-mg/kg of body weight dose of plazomicin as a 30-min intravenous infusion. Total clearance declined with renal impairment, resulting in 1.98-fold and 4.42-fold higher plazomicin exposures, as measured by the area under the concentration-time curve from 0 h to infinity, in subjects with moderate and severe impairment, respectively, than in subjects with normal renal function. (This study has been registered at ClinicalTrials.gov under identifier NCT01462136.).

[Psoas abscess due to Candida tropicalis: a case report]. / Abcès de psoas à Candida tropicalis : à propos d'un cas.

Psoas abscess is a rare infection, difficult to diagnose, which can be primary or secondary, it is often caused by a bacterial micro-organism (Staphylococcus aureus, Escherichia coli), and in rare cases by a fungal micro-organism (Candida). We report an exceptional case of Candida tropicalis psoas abscess in a 52-year-old man with no history of pathology who had inflammatory lower back pain with fever and general deterioration. The biological assessment showed a renal insufficiency and a biological inflammatory syndrome, a computed tomography made in urgency was in favor of a psoas abscess. The bacteriological study of percutaneous drainage product allowed to isolate Candida tropicalis.

Isavuconazole treatment for rare fungal diseases and for invasive aspergillosis in patients with renal impairment: Challenges and lessons of the VITAL trial.

Invasive fungal disease (IFD) confers a substantial risk for morbidity and mortality to immunocompromised patients. Invasive aspergillosis (IA) is the most common IFD caused by moulds but the prevalence of other rare mould diseases, such as mucormycosis, hyalohyphomycosis and phaeohyphomycosis, may be increasing. Treatments are available for IA, but evidence to support efficacy and safety of antifungal agents for rare IFDs, or for IFDs in special patient populations, is limited or lacking. The VITAL trial was conducted to assess the efficacy and safety of isavuconazole for the treatment of patients with IA and renal impairment, or with IFDs caused by rare moulds, yeasts or dimorphic fungi. These patients stand to benefit most from a new treatment option but are unlikely to be included in a randomised, controlled trial. In this article, we review the challenges faced in the design and conduct of the VITAL trial. We also review the findings of VITAL, which included evidence of the efficacy and safety of isavuconazole. Finally, we consider the importance of trials such as VITAL to inform therapeutic decision making for clinicians faced with the challenge of treating patients with rare IFDs and as one paradigm of how to determine efficacy and safety of new drugs for rare and resistant infections without a suitable comparator.

QuantiFERON-TB Gold In-Tube in Saudi Arabia benchmarked with other sites of the Middle East: A meta-analysis review.

INTRODUCTION: Screening for Latent Tuberculosis Infections (LTBI) constitutes a key step in health surveillance programs especially among adults of high-risk groups. To our knowledge, this is the first systematic and meta-analysis review that aims to critically assess and compare the agreement of QuantiFERON-TB Gold In-Tube (QFT-GIT) and Tuberculin Skin Testing (TST) among adults of high-risk groups in Saudi Arabia and compare results with other sites of the Middle East. METHODOLOGY: Kappa estimates were meta-analyzed using random effect model and several subgroup analyzes were performed to explain overall heterogeneity. Funnel plot, Begg's and Egger's tests were employed to assess overall publication bias. RESULTS: 18 studies were meta-analyzed, comprising 5070 adults of high-risk groups. Pooled kappa estimates from Saudi Arabia (κ = 0.29, 95% CI: 0.16, 0.41) showed lower rate of agreement compared to other sites of the Middle East (κ = 0.33, 95% CI: 0.25, 0.41). However, a significant level of heterogeneity (I2 = 96.7%, p > 0.001) were identified across collected evidence. Begg's and Egger's tests confirmed absence of significant publication bias in this review (p = 0.49 and p = 0.16, respectively). CONCLUSION: This work revealed fair to poor agreement between TST and QFT-GIT, indicating that these two tests are not interchangeable in such settings. Substantial evidence is still needed before considering the sole use of QFT-GIT as an alternative to TST in these populations. Moreover, there is an urgent need for longitudinal studies in Saudi Arabia and the Middle East to accurately assess precision of LTBI diagnosis.

Optimal teicoplanin dosage regimens for methicillin-resistant Staphylococcus aureus infections in endocarditis patients and renal failure patients.

This study aimed to assess whether traditional initial loading and maintenance doses of teicoplanin were appropriate in endocarditis and renal failure patients with methicillin-resistant Staphylococcus aureus (MRSA) infections and to recommend optimal dosage regimens. Pharmacokinetic parameters and physicochemical properties of teicoplanin were performed to develop pharmacokinetic models using GastroPlusTM. Concentration-time curves of teicoplanin in endocarditis and renal failure patients with MRSA infections were simulated by changing clearance (CL) and volume of distribution of the central compartment (Vc). Different teicoplanin dosage regimens were assessed according to the target trough concentration, and optimal teicoplanin dosage regimens were recommended. Dosage regimen of four teicoplanin doses of 6 mg/kg q12 h followed by 6 mg/kg qd is recommended for renal failure patients infected by MRSA. And optimal dosage regimen is five teicoplanin doses of 15 mg/kg q12 h followed by doses of 12 mg/kg qd for endocarditis patients infected by MRSA.

Risk factors, characteristics, and outcomes of candidemia in an adult intensive care unit in Turkey.

Thirty-six patients with candidemia and 37 control patients were included consecutively to determine the characteristics of candidemia episodes. The patients with candidemia had higher mortality with higher Sequential Organ Failure Assessment scores and frequency of use of a central venous catheter, total parenteral nutrition, and broad-spectrum antibiotics; chronic renal failure with replacement therapy; and longer stay in an intensive care unit. Candida albicans was the predominant species followed by Candida glabrata, Candida tropicalis, and Candida parapsilosis. All isolates of C glabrata were itraconazole-resistant.

Echinocandins Compared to Fluconazole for Candidemia of a Urinary Tract Source: A Propensity Score Analysis.

BACKGROUND: Whether echinocandins could be used to treat candidemia of a urinary tract source (CUTS) is unknown. We aimed to provide current epidemiological information of CUTS and to compare echinocandin to fluconazole treatment on CUTS outcomes. METHODS: A multicenter study of adult patients with candidemia was conducted in 9 hospitals. CUTS was defined as a candidemia with concomitant candiduria by the same organism associated with significant urological comorbidity. The primary outcome assessed was clinical failure (defined by 7-day mortality or persistent candidemia) in patients treated with either an echinocandin or fluconazole. A propensity score was calculated and then entered into a regression model. RESULTS: Of 2176 episodes of candidemia, 128 were CUTS (5.88%). Most CUTS cases were caused by Candida albicans (52.7%), followed by Candida glabrata (25.6%) and Candida tropicalis (16.3%). Clinical failure occurred in 7 patients (20%) treated with an echinocandin and in 15 (17.1%) treated with fluconazole (P = .730). Acute renal failure (adjusted odds ratio [AOR], 3.01; 95% confidence interval [CI], 1.01-8.91; P = .047) was the only independent factor associated with clinical failure, whereas early urinary tract drainage procedures (surgical, percutaneous, or endoscopic) were identified as protective (AOR, 0.08; 95% CI, .02-.31; P < .001). Neither univariate nor multivariate analysis showed that echinocandin therapy altered the risk of clinical failure. CONCLUSIONS: Initial echinocandin therapy was not associated with clinical failure in patients with CUTS. Notably, acute renal failure predicted worse outcomes and performing an early urologic procedure was a protective measure.

Citrobacter braakii Bacteremia: Case Report and Review of the Literature.

Bacteremia is frequently caused by gram-positive organisms such as Staphylococcus aureus or ß hemolytic streptococci. While there is adequate information for the diagnosis and management of these common bacteria, less information is available to address bacteremia that is caused by uncommon bacteria such as Citrobacter. Citrobacter species are gram-negative bacilli that have been noted to cause infections in immune compromised patients. The re-speciation of Citrobacter by its varied genetic composition has produced 11 distinct species. While C. braakii is part of the genome species 6 of the previous Citrobacter freundii complex, there is a lack of definitive research on the subject of Citrobacter bacteremia caused by lesser- known species. We report an unusual case of Citrobacter braakii bacteremia in a patient with multiple comorbidities that presented to the hospital with cellulitis and pleural effusion. Blood cultures grew Citrobacter braakii. Despite good response to antibiotic treatment, the patient's infection proved to be persistent and he succumbed to the cirrhosis of the liver and subsequent renal failure. Multiple and fatal underlying disease processes seem to worsen the likelihood of recovery from unusual infections. We believe our case report can add to the limited data available for C. braakii.

Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial.

BACKGROUND AND OBJECTIVES: The generation of key uremic nephrovascular toxins, indoxyl sulfate (IS), and p-cresyl sulfate (PCS), is attributed to the dysbiotic gut microbiota in CKD. The aim of our study was to evaluate whether synbiotic (pre- and probiotic) therapy alters the gut microbiota and reduces serum concentrations of microbiome-generated uremic toxins, IS and PCS, in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Predialysis adult participants with CKD (eGFR=10-30 ml/min per 1.73 m(2)) were recruited between January 5, 2013 and November 12, 2013 to a randomized, double-blind, placebo-controlled, crossover trial of synbiotic therapy over 6 weeks (4-week washout). The primary outcome was serum IS. Secondary outcomes included serum PCS, stool microbiota profile, eGFR, proteinuria-albuminuria, urinary kidney injury molecule-1, serum inflammatory biomarkers (IL-1ß, IL-6, IL-10, and TNF-α), serum oxidative stress biomarkers (F2-isoprostanes and glutathione peroxidase), serum LPS, patient-reported health, Gastrointestinal Symptom Score, and dietary intake. A prespecified subgroup analysis explored the effect of antibiotic use on treatment effect. RESULTS: Of 37 individuals randomized (age =69±10 years old; 57% men; eGFR=24±8 ml/min per 1.73 m(2)), 31 completed the study. Synbiotic therapy did not significantly reduce serum IS (-2 µmol/L; 95% confidence interval [95% CI], -5 to 1 µmol/L) but did significantly reduce serum PCS (-14 µmol/L; 95% CI, -27 to -2 µmol/L). Decreases in both PCS and IS concentrations were more pronounced in patients who did not receive antibiotics during the study (n=21; serum PCS, -25 µmol/L; 95% CI, -38 to -12 µmol/L; serum IS, -5 µmol/L; 95% CI, -8 to -1 µmol/L). Synbiotics also altered the stool microbiome, particularly with enrichment of Bifidobacterium and depletion of Ruminococcaceae. Except for an increase in albuminuria of 38 mg/24 h (P=0.03) in the synbiotic arm, no changes were observed in the other secondary outcomes. CONCLUSION: In patients with CKD, synbiotics did not significantly reduce serum IS but did decrease serum PCS and favorably modified the stool microbiome. Large-scale clinical trials are justified.

Risk of haemolytic uraemic syndrome caused by shiga-toxin-producing Escherichia coli infection in adult women in Japan.

Shiga-toxin-producing Escherichia coli (STEC) infections usually cause haemolytic uraemic syndrome (HUS) equally in male and female children. This study investigated the localization of globotriaosylceramide (Gb3) in human brain and kidney tissues removed from forensic autopsy cases in Japan. A fatal case was used as a positive control in an outbreak of diarrhoeal disease caused by STEC O157:H7 in a kindergarten in Urawa in 1990. Positive immunodetection of Gb3 was significantly more frequent in female than in male distal and collecting renal tubules. To correlate this finding with a clinical outcome, a retrospective analysis of the predictors of renal failure in the 162 patients of two outbreaks in Japan was performed: one in Tochigi in 2002 and the other in Kagawa Prefecture in 2005. This study concludes renal failure, including HUS, was significantly associated with female sex, and the odds ratio was 4·06 compared to male patients in the two outbreaks. From 2006 to 2009 in Japan, the risk factor of HUS associated with STEC infection was analysed. The number of males and females and the proportion of females who developed HUS were calculated by age and year from 2006 to 2009. In 2006, 2007 and 2009 in adults aged >20 years, adult women were significantly more at risk of developing HUS in Japan.

Demographics and prevalence of positive QuantiFERON-TB Gold In-Tube test in renal transplant candidates.

BACKGROUND: Latent tuberculosis infection (LTBI) screening prior to solid organ transplantation is standard of care. QuantiFERON-TB Gold In-Tube (QFT-GIT) test is the preferred diagnostic test for renal transplant candidates (RTC). QFT-GIT reversions and the potential delay of living-donor kidney transplantation (LDKT) because of QFT-GIT positivity have not been examined previously in RTC. METHODS: We evaluated the prevalence of positive QFT-GIT in RTC from January 1 through December 31, 2011. In addition, we examined the demographic and renal disease data differences between QFT-GIT-positive and -negative patients, changes in QFT-GIT results, and positive QFT-GIT results reverting to negative. Lastly, we evaluated if QFT-GIT-positive patients were less likely to undergo LDKT within 6 months of QFT-GIT testing. RESULTS: In total, 722 RTC were analyzed, 16% of whom had positive QFT-GIT. The QFT-GIT-positive patients were more likely to be older and foreign-born, P < 0.0001. Haitians had the highest prevalence. Of the 119 QFT-GIT-positive patients, 25% had low/intermediate-positive results and were more likely to revert to negative, compared with patients with high-positive QFT-GIT results (50% vs. 0%, P = 0.01). A trend was seen toward fewer QFT-GIT-positive patients undergoing LDKT, compared with QFT-GIT-negative patients (0% vs. 3%, P = 0.09). CONCLUSIONS: Our high prevalence was likely a result of the high number of foreign-born RTC. Half of our small subset of low/intermediate-positive QFT-GIT patients reverted to negative. QFT-GIT-positive patients were more likely to have their LDKT delayed.

Aborto séptico por Clostridium perfringens complicado con shock séptico / Septic abortion due to Clostridium perfringens complicated with septic shock

ANTECEDENTES: La sepsis por Clostridios es una entidad poco frecuente que conlleva una mortalidad del 8090% a pesar del tratamiento antibiótico y quirúrgico. A pesar de que la mayoría de los casos de septicemia secundaria a Clostridios se originan en el aparato genital femenino tras un aborto séptico, solo un pequeño porcentaje de abortos sépticos (1%) se siguen de septicemia. CASO CLÍNICO: Gestante de 15 semanas que acude a urgencias por rotura prematura de membranas pretérmino. Ante el deseo de la paciente se mantiene actitud conservadora con antibioterapia iv, produciéndose a las pocas horas el aborto de forma espontánea junto con aparición de signos de infección. Rápidamente la paciente evoluciona a sepsis grave, y ante la sospecha de aborto séptico se efectúa histerectomía. Tras la intervención ingresa en situación de shock séptico con insuficiencia renal, hepática y respiratoria. Durante el ingreso se confirma Clostridium perfringens como agente responsable del proceso séptico. Finalmente la paciente es dada de alta definitiva tras seis meses, una vez resueltas las alteraciones derivadas del proceso séptico.

BACKGROUND: Clostridial sepsis is a rare condition which carries a mortality of 80-90% despite antibiotic and surgical treatment. Although most cases of septicemia due to Clostridium are originated in female genital tract after septic abortion, only a small percentage of septic abortions (1%) are followed by septicemia. CLINICAL CASE: Our case is about a 15 weeks pregnant woman attended the emergency room for preterm premature rupture of membranes. Due to the desire of the patient we proceed conservative treatment with antibiotics iv, in the following few hours the abortion develops spontaneously along with signs of infection. Rapidly the patient progresses into a severe sepsis, due to suspected septic abortion, the patient is intervened urgently by hysterectomy. After the intervention she enters into septic shock state with respiratory, kidney and liver failure. During the admission Clostridium perfringens is confirmed as a causative agent for septic process. Finally the patient is discharge after six months once resolved all complications arising from septic process.

Suboptimal antimicrobial drug exposure in patients with renal impairment.

BACKGROUND: Recommendations on drug dose adjustment in patients with renal impairment may vary between the references. It is often unknown which approach the dosing schemes were based on and what drug exposure is likely to be achieved. OBJECTIVE: To develop a simple method to evaluate recommended dosing schemes for patients with renal impairment, to apply this method to selected antibacterial drugs in order to evaluate expected drug concentrations using dosing schemes recommended for patients with severe infections, and to evaluate the expected consequences. SETTING: This was a theoretical study, which was based on data from published clinical trials. METHODS: Clinically established dosing schemes for 46 antibacterial drugs, as recommended for patients with renal impairment in the Summary of Product Characteristics, were analysed using a newly developed graphical method. Consistency of the dosing schemes with two general dose adjustment rules, the proportional rule and the eliminated fraction rule, was determined and drug exposure was predicted. MAIN OUTCOME MEASURE: Predicted drug exposure. Consistency of recommended dosing schemes with the general dose adjustment rules. RESULTS: Only 30% of the recommended dosing schemes were associated with similar average concentrations as expected in patients with normal renal function (44 % were associated with higher and 26% with lower concentrations). The highest median exposure was found in beta-lactams (170%, range 58-443%, for creatinine clearance of <15 ml/min, and 155%, range 54-232%, for creatinine clearance of 15 to <30 ml/min), where the medians were significantly different from 100% (P < 0.02). Consistency with a dosing rule was found in 59% of the dosing schemes (proportional rule 46%, eliminated fraction rule 50%, both rules 4%). CONCLUSIONS: Relative low exposure was found for several drugs, including ceftazidime, cefotaxime, imipenem, erythromycin, ciprofloxacin, levofloxacin, and teicoplanin, where dosing schemes should be reconsidered or used only in clinical situations where a lower than maximum exposure appears adequate. General application of the proportional rule for calculating drug dose adjustments would lead to lower than clinically established dose practice for 44% of drugs.

Population pharmacokinetic-pharmacodynamic target attainment analysis of sulbactam in patients with impaired renal function: dosing considerations for Acinetobacter baumannii infections.

UNLABELLED: This study aimed to perform a pharmacokinetic (PK)-pharmacodynamic (PD) target attainment analysis of sulbactam against Acinetobacter baumannii in patients with impaired renal function. The PK data (188 plasma samples and 27 urine samples) were modeled simultaneously. The mean population parameters were CLr (l/h) = 0.0792 × CLcr (ml/min), CLnr (l/h) = 2.35, Vc (l) = 12.2, Q (l/h) = 4.68 and Vp (l) = 4.44, where CLr and CLnr are the renal and non-renal clearances, Vc and Vp are the distribution volumes of the central and peripheral compartments and Q is intercompartmental clearance. The creatinine clearance (CLcr) was the most significant covariate. The determined MIC of sulbactam against A. baumannii clinical isolates (n = 27) was 0.75-6.0 µg/ml with MIC50 and MIC90 of 1 and 4 µg/ml, respectively. For sulbactam regimens, a Monte Carlo simulation estimated the probabilities of attaining the bactericidal target (60% of the time above the MIC) and determined the PK-PD breakpoints (the highest MICs at which the probabilities were 90% or more). In a patient with a CLcr of 15 ml/min, a regimen of 1 g twice daily achieved a 90% or more probability against the A. baumannii isolate population; however, 2 g four times daily was needed for a 90% or more probability in a patient with a CLcr of 90 ml/min. The results of the PK-PD target attainment analysis are useful when choosing the sulbactam regimen based on the CLcr of the patient and the susceptibility of A. baumannii. REGISTRATION NUMBER: UMIN000007356.