Response-Guided Therapy With Cefotaxime, Ceftriaxone, or Ciprofloxacin for Spontaneous Bacterial Peritonitis: A Randomized Trial: A Validation Study of 2021 AASLD Practice Guidance for SBP.

INTRODUCTION: For the treatment of spontaneous bacterial peritonitis (SBP), cefotaxime, ceftriaxone, and ciprofloxacin were used as first-line agents. However, considering the increasing rate of antibiotic resistance, it is unclear which of these drugs can be initially recommended. This study aimed to compare the current efficacy of the 3 antibiotics, namely cefotaxime, ceftriaxone, and ciprofloxacin, for the treatment of SBP in patients with cirrhosis with ascites, when guided by therapeutic responses. METHODS: This study was a multicenter, prospective, randomized controlled trial. The inclusion criteria were 16- to 75-year-old patients with liver cirrhosis with ascites, having polymorphonuclear cell count of >250/mm 3 . We performed a follow-up paracentesis at 48 hours to decide continuing or changing the assigned antibiotics and then assessed the resolution rates at 120 and 168 hours of treatment. RESULTS: A total of 261 patients with cirrhosis who developed SBP were enrolled. Most of the patients were diagnosed as those with SBP within 48 hours of admission. The resolution rates at 120 hours, which is the primary endpoint, were 67.8%, 77.0%, and 73.6% in the cefotaxime, ceftriaxone, and ciprofloxacin groups, respectively ( P = 0.388), by intension-to-treat analysis. The 1-month mortality was similar among the groups ( P = 0.770). The model for end-stage liver disease score and the SBP resolution were significant factors for survival. CONCLUSION: The efficacy of empirical antibiotics, such as cefotaxime, ceftriaxone, and ciprofloxacin, against SBP was not significantly different. In addition, these antibiotics administered based on response-guided therapy were still efficacious as initial treatment for SBP, especially in those with community-acquired infections.

Penicillin- and Cephalosporin-Resistant Pneumococcal Meningitis: Treatment in the Real World and in Guidelines.

To report on the therapy used for penicillin- and cephalosporin-resistant pneumococcal meningitis, we conducted an observational cohort study of patients admitted to our hospital with pneumococcal meningitis between 1977 and 2018. According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations, we defined pneumococci as susceptible and resistant to penicillin with MIC values of ≤0.06 mg/L and > 0.06 mg/L, respectively; the corresponding values for cefotaxime (CTX) were ≤0.5 mg/L and >0.5 mg/L. We treated 363 episodes of pneumococcal meningitis during the study period. Of these, 24 had no viable strain, leaving 339 episodes with a known MIC for inclusion. Penicillin-susceptible strains accounted for 246 episodes (73%), penicillin-resistant strains for 93 (27%), CTX susceptible for 58, and CTX resistant for 35. Nine patients failed or relapsed and 69 died (20%), of whom 22% were among susceptible cases and 17% were among resistant cases. During the dexamethasone period, mortality was equal (12%) in both susceptible and resistant cases. High-dose CTX (300 mg/Kg/day) helped to treat failed or relapsed cases and protected against failure when used as empirical therapy (P = 0.02), even in CTX-resistant cases. High-dose CTX is a good empirical therapy option for pneumococcal meningitis in the presence of a high prevalence of penicillin and cephalosporin resistance, effectively treating pneumococcal strains with MICs up to 2 mg/L for either penicillin or CTX.

Multidrug-resistant Klebsiella pneumoniae harboring extended spectrum ß-lactamase encoding genes isolated from human septicemias.

Klebsiella pneumoniae is a major pathogen implicated in nosocomial infections. Extended-spectrum ß-lactamase (ESBL)-producing K. pneumoniae isolates are a public health concern. We aim to characterize the type of ß-lactamases and the associated resistance mechanisms in ESBL-producing K. pneumoniae isolates obtained from blood cultures in a Portuguese hospital, as well as to determine the circulating clones. Twenty-two cefotaxime/ceftazidime-resistant (CTX/CAZR) K. pneumoniae isolates were included in the study. Identification was performed by MALDI-TOF MS and the antimicrobial susceptibility testing by disk-diffusion. The screening test for ESBL-production was performed and ESBL-producer isolates were further characterized. The presence of different beta-lactamase genes (blaCTX-M, blaSHV, blaTEM, blaKPC, blaNDM, blaVIM, blaOXA-48, blaCMY-2, blaDHA-1, blaFOX, blaMOX, and blaACC) was analyzed by PCR/sequencing in ESBL-producer isolates, as well as the presence of other resistance genes (aac(6')-Ib-cr, tetA/B, dfrA, qnrA/B/S, sul1/2/3) or integron-related genes (int1/2/3). Multilocus-sequence-typing (MLST) was performed for selected isolates. ESBL activity was detected in 12 of the 22 CTX/CAZR K. pneumoniae isolates and 11 of them carried the blaCTX-M-15 gene (together with blaTEM), and the remaining isolate carried the blaSHV-106 gene. All the blaCTX-M-15 harboring isolates also contained a blaSHV gene (blaSHV-1, blaSHV-11 or blaSHV-27 variants). Both blaSHV-27 and blaSHV-106 genes correspond to ESBL-variants. Two of the CTX-M-15 producing isolates carried a carbapenemase gene (blaKPC2/3 and blaOXA-48) and showed imipenem resistance. The majority of the ESBL-producing isolates carried the int1 gene, as well as sulphonamide-resistance genes (sul2 and/or sul3); the tetA gene was detected in all eight tetracycline-resistant isolates. Three different genetic lineages were found in selected isolates: ST348 (one CTX-M-15/TEM/SHV-27/KPC-2/3-producer isolate), ST11 (two CTX-M-15/TEM/SHV-1- and CTX-M-15-TEM-SHV-11-OXA-48-producer isolates) and ST15 (one SHV-106/TEM-producer isolate). ESBL enzymes of CTX-M-15 or SHV-type are detected among blood K. pneumoniae isolates, in some cases in association with carbapenemases of KPC or OXA-48 type.

No significant difference between ceftriaxone and cefotaxime in the emergence of antibiotic resistance in the gut microbiota of hospitalized patients: A pilot study.

BACKGROUND: Ceftriaxone and cefotaxime share a similar antibacterial spectrum and similar indications but have different pharmacokinetic characteristics. Ceftriaxone is administered once daily and 40% of its clearance is by biliary elimination, whereas cefotaxime requires three administrations per day and shows less than 10% biliary elimination. The high biliary elimination of ceftriaxone suggests a greater impact of this antibiotic on the gut microbiota than cefotaxime. The objective of this study was to compare the impact of ceftriaxone and cefotaxime on the gut microbiota. METHODS: A prospective clinical trial was performed that included 55 patients treated with intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for at least 3 days. Three fresh stool samples were collected from each patient (days 0, 3, and 7 or at the end of intravenous treatment) to assess the emergence of third-generation cephalosporin (3GC)-resistant Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa, toxigenic Clostridioides difficile, and vancomycin-resistant enterococci. RESULTS: The emergence of 3GC-resistant gram-negative enteric bacilli (Enterobacteriaceae) (5.9% vs 4.7%, p > 0.99), Enterococcus spp, and non-commensal microorganisms did not differ significantly between the groups. Both antibiotics reduced the counts of total gram-negative enteric bacilli and decreased the cultivable diversity of the microbiota, but the differences between the groups were not significant. CONCLUSION: No significant difference was observed between ceftriaxone and cefotaxime in terms of the emergence of resistance.

High prevalence of multidrug resistant ESBL- and plasmid mediated AmpC-producing clinical isolates of Escherichia coli at Maputo Central Hospital, Mozambique.

BACKGROUND: Epidemiological data of cephalosporin-resistant Enterobacterales in Sub-Saharan Africa is still restricted, and in particular in Mozambique. The aim of this study was to detect and characterize extended-spectrum ß-lactamase (ESBL) - and plasmid-mediated AmpC (pAmpC)-producing clinical strains of Escherichia coli at Maputo Central Hospital (MCH), a 1000-bed reference hospital in Maputo, Mozambique. METHODS: A total of 230 clinical isolates of E. coli from urine (n = 199) and blood cultures (n = 31) were collected at MCH during August-November 2015. Antimicrobial susceptibility testing was performed by the disc diffusion method and interpreted according to EUCAST guidelines. Isolates with reduced susceptibility to 3rd generation cephalosporins were examined further; phenotypically for an ESBL-/AmpC-phenotype by combined disc methods and genetically for ESBL- and pAmpC-encoding genes by PCR and partial amplicon sequencing as well as genetic relatedness by ERIC-PCR. RESULTS: A total of 75 isolates with reduced susceptibility to cefotaxime and/or ceftazidime (n = 75) from urine (n = 58/199; 29%) and blood (n = 17/31; 55%) were detected. All 75 isolates were phenotypically ESBL-positive and 25/75 (33%) of those also expressed an AmpC-phenotype. ESBL-PCR and amplicon sequencing revealed a majority of blaCTX-M (n = 58/75; 77%) dominated by blaCTX-M-15. All AmpC-phenotype positive isolates (n = 25/75; 33%) scored positive for one or more pAmpC-genes dominated by blaMOX/FOX. Multidrug resistance (resistance ≥ three antibiotic classes) was observed in all the 75 ESBL-positive isolates dominated by resistance to trimethoprim-sulfamethoxazole, ciprofloxacin and gentamicin. ERIC-PCR revealed genetic diversity among strains with minor clusters indicating intra-hospital spread. CONCLUSION: We have observed a high prevalence of MDR pAmpC- and/or ESBL-producing clinical E. coli isolates with FOX/MOX and CTX-Ms as the major ß-lactamase types, respectively. ERIC-PCR analyses revealed genetic diversity and some clusters indicating within-hospital spread. The overall findings strongly support the urgent need for accurate and rapid diagnostic services to guide antibiotic treatment and improved infection control measures.

[A multicentric clinical study on clinical characteristics and drug sensitivity of children with pneumococcal meningitis in China].

Objective: To understand clinical characteristics of children with pneumococcal meningitis (PM) in China and to analyze the drug sensitivity of Streptococcus pneumoniae isolates and associated impacts on death and sequelae. Methods: The clinical data, follow-up results and antimicrobial sensitivity of isolated strains of 155 children (including 98 males and 57 females, age ranged from 2 months to 15 years) with PM in 10 tertiary-grade A class hospitals of Infectious Diseases Surveillance of Pediatrics (ISPED) from 2013 to 2017 were collected and analyzed retrospectively. Patients were divided into different groups according to the following standards: ≤1 year old group,>1-3 years old group and >3 years old group according to age; death group and non-death group according to the death within 30 days after PM diagnosis; complication group and non-complication group according to the abnormal cranial imaging diagnosis; sequelae group and no-sequelae group according to the follow-up results. Bonfereoni chi-square segmentation and Kruskal-Wallis H test were used for statistical analysis. Results: There were 64 cases (41.3%) in the ≤1 year old group, 39 cases in the >1-3 years old group (25.2%), and 52 cases (33.5%) in the >3 years old group. The most common clinical manifestation was fever (151 cases, 97.4%). The mortality was 16.8% (26/155) during hospitalization. The neurological complication rate was 49.7% (77/155) during hospitalization, including the most common complication, subdural effusion and (or) empyema in 50 cases (32.3%) and hearing impairment in 6 cases. During follow-up after discharge, no death was found and focal neurological deficits were found in 47 cases (30.3%), including the frequent neurological sequelae: cognitive and mental retardation of different degree in 22 cases and hearing impairment in 14 cases (9.0%). The rate of cure and improvement on discharge was 74.8% (116/155) and the lost to follow-up rate was 8.4% (13/155). The proportions of died cases, neurological complications during hospitalization and proportions of peripheral white blood cell count <12 × 10(9)/L before admission in ≤1 year old group were significantly higher than those in >3 years old group (25.0% (16/64) vs. 5.8% (3/52), 75.0% (48/64) vs. 25.0% (13/52), 48.4% (31/64) vs. 15.4% (8/52), χ(2)=7.747, 28.767, 14.044; P=0.005, 0.000, 0.000). The proportions of headache, vomiting, neck resistance and high risk factors of purulent meningitis in >3 years old group were significantly higher than those in ≤ 1 year old group (67.3%(35/52) vs. 1.6%(1/64), 80.8% (42/52) vs. 48.4% (31/64), 69.2% (36/52) vs. 37.5% (24/64), 55.8% (29/52) vs. 14.1%(9/64), χ(2)=57.940, 12.856, 11.568, 22.656; P=0.000, 0.000, 0.001, 0.000). Streptococcus pneumoniae isolates were completely sensitive to vancomycin (100.0%, 152/152), linezolid (100.0%, 126/126), moxifloxacin (100.0%, 93/93) and ofloxacin (100.0%,41/41); highly sensitive to levofloxacin (99.3%, 142/143) and ertapenem (84.6%, 66/78); moderately sensitive to ceftriaxone (48.4%, 45/93), cefotaxime (40.0%, 44/110) and meropenem (38.0%, 38/100); less sensitive to penicillin (19.6%, 27/138) and erythromycin (4.2%, 5/120). The proportions of non-sensitive strains of penicillin (21/21) and meropenem (17/18) in the death group were significantly higher than those (90/117, 45/82) in the survived group(χ(2)=4.648 and 9.808, P=0.031 and 0.002). Conclusions: The children's PM is mainly found in infants under 3 years old in China. Death and neurological complications are more common in PM children under 1 year old. The clinical manifestations and peripheral blood inflammatory markers of PM patients under 1 year old are not typical. Fever is the most common clinical manifestation and subdural effusion and (or) empyema is the most common complication. Long-term hearing impairment is common in PM and the follow-up time must be prolonged. The dead PM cases had high in sensitive rates to penicillin and meropenem.

Effective Oral Combination Treatment for Extended-Spectrum Beta-Lactamase-Producing Escherichia coli.

Background: Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) is increasing worldwide. The drugs of choice for treatment of ESBLs are parenteral carbapenems. The aim of this study was to evaluate the in vitro and in vivo efficacy of a new combination of oral cephalosporins and amoxicillin/clavulanate in treatment of ESBL-EC. Methods: A total of 150 ESBL-EC samples were collected over 1 year from two referral centers. Synergistic studies of cephalosporins and amoxicillin/clavulanate were performed in vitro using disk approximation and disk replacement methods. Combination treatment was assessed in vivo on 20 ESBL-EC urinary tract infection (UTI) patients. Results: ESBL-EC isolates were confirmed in 150 patients with a mean age of 46.67 years, 75.2% of them being women. Antibiotic susceptibility testing of isolates indicated high resistance rate to oral antibiotics. The frequency of positive synergy and mean distance of synergy between cephalosporins and amoxicillin/clavulanate was significantly higher with cefotaxime and cefixime compared with cefpodoxime, cefdinir, and ceftazidime using disk approximation and disk replacement methods (p < 0.05). Addition of amoxicillin/clavulanate enhanced the susceptibility rate with cefixime from 8.6% to 86.3%, significantly higher than with other cephalosporins (p < 0.0005). Cefixime and amoxicillin/clavulanate synergy was not affected by age, gender, hospital, department, sample type, or bacterial load. Eighteen of 20 ESBL-EC-positive UTI patients had a positive in vitro synergy test and complete clinical and microbiological resolution after completion of cefixime and amoxicillin/clavulanate oral treatment course. Conclusions: Cefixime and amoxicillin/clavulanate combination therapy could be an effective oral outpatient treatment option for ESBL-EC. In vitro synergistic testing is simple and predictive of successful treatment.

Premature Infant with Haemophilus parainfluenzae Sepsis: Case Report and Literature Review.

Haemophilus parainfluenzae is an unusual causative organism of invasive bacterial infection in adults and children. Mortality and morbidity secondary to Haemophilus parainfluenzae have been documented in the literature. We present a rare case of a premature infant with early onset sepsis caused by Haemophilus parainfluenzae, who was born to a primigravida with chorioamnionitis. The infant was successfully treated for 10 days with antibiotics with no complications.

Identifying the mechanism underlying treatment failure for Salmonella Paratyphi A infection using next-generation sequencing - a case report.

BACKGROUND: Salmonella is a notorious pathogen that causes gastroenteritis in humans and the emergence of resistance to third-generation cephalosporins and azithromycin have raised concern. There has been rare case of Salmonella Paratyphi A infection accompanied by spondylitis. Here, we report a case of initial antibiotic treatment failure in a Korean man with Salmonella Paratyphi A infection and conducted next-generation sequencing (NGS) to determine the cause of failure of initial treatment for Salmonella Paratyphi A infection. CASE PRESENTATION: A 70-year-old man was admitted to Chosun University Hospital with reported consistent low back pain with a history of having 5 days of chills and fever in another hospital a month ago. He was administered ceftriaxone (2 g daily) for 18 days including initial treatment to cover Salmonella enterica. The antimicrobial susceptibility test using MIC plate, found that the identified organism was resistant to ciprofloxacin and nalidixic acid. Moreover, the Salmonella Paratyphi A isolates were found to have an MIC > 16 mg/L for azithromycin, as he had resistance to both azithromycin and nalidixic acid, the treatment was switched to a combination of ciprofloxacin and cefotaxime. We carried out next-generation sequencing (NGS) to determine the cause of failure of initial treatment for Salmonella Paratyphi A infection. NGS showed that the amino acid substitution GyrA S83F and the expression of multiple RNA-family efflux pumps led to a high-level resistance to quinolone. No genes related to ceftriaxone resistance, such as CTX-M, CMY-2, or other extended-spectrum beta-lactamases were identified in Salmonella enterica Paratyphi A using NGS. The GyrA S83F mutation and the expression of multiple RNA-family efflux pumps may have contributed to the treatment failure of ceftriaxone, even though the MIC of the isolate to ceftriaxone was less than 1. CONCLUSION: This case involved a Salmonella Paratyphi A infection accompanied by spondylitis. To our knowledge, this is the first report to elucidate the mechanism underlying antimicrobial resistance using NGS.

Increasing Antimicrobial Resistance in Nontyphoidal Salmonella Isolates in Australia from 1979 to 2015.

Australia has high and increasing rates of salmonellosis. To date, the serovar distribution and associated antimicrobial resistance (AMR) patterns of nontyphoidal Salmonella enterica (NTS) in Australia have not been assessed. Such information provides critical knowledge about AMR in the food chain and informs decisions about public health. We reviewed longitudinal data on NTS in two Australian states over a 37-year period, between 1979 and 2015, and antimicrobial resistance since 1984. Overall, 17% of isolates were nonsusceptible to at least one antimicrobial, 4.9% were nonsusceptible to ciprofloxacin, and 0.6% were nonsusceptible to cefotaxime. In total, 2.5% of isolates were from invasive infections, with no significant difference in AMR profiles between invasive and noninvasive isolates. Most isolates with clinically relevant AMR profiles were associated with travel, particularly to Southeast Asia, with multiple "incursions" of virulent and resistant clones into Australia. Our findings represent the largest longitudinal surveillance system for NTS in Australia and provide valuable public health knowledge on the trends and distribution of AMR in NTS. Ongoing surveillance is critical to identify local emergence of resistant isolates.

A Cohort Study of Risk Factors That Influence Empirical Treatment of Patients with Acute Pyelonephritis.

The aim of the current study was to compare community-acquired acute pyelonephritis (CA-APN) with health care-associated acute pyelonephritis (HCA-APN), describe the outcomes, and identify variables that could predict antimicrobial susceptibility. We conducted an observational study that included all consecutive episodes of acute pyelonephritis (APN) in adults during 2014 at a Spanish university hospital. From each episode, demographic data, comorbidities, clinical presentation, microbiological data, antimicrobial therapy, and outcome were recorded. A multivariable logistic regression model was performed to define the variables associated with antimicrobial resistance. A total of 607 patients, 503 (82.9%) with CA-APN and 104 (17.1%) with HCA-APN, were included in the study. Patients with HCA-APN were older than patients with CA-APN (70.4 versus 50.6 years; P < 0.001) and had higher rates of previous urinary tract infections (UTIs) (56.5% versus 24.5%; P < 0.001) and previous antibiotic use (56.8% versus 22.8%; P < 0.001). Escherichia coli was more frequently isolated from patients with CA-APN than from patients with HCA-APN (79.9% versus 50.5%; P < 0.001). The rates of resistance of Escherichia coli strains from CA-APN patients versus HCA-APN patients were as follows: amoxicillin-clavulanic acid, 22.4% versus 53.2% (P = 0.001); cefuroxime, 7.7% versus 43.5% (P = 0.001); cefotaxime, 4.3% versus 32.6% (P < 0.001); ciprofloxacin, 22.8% versus 74.5% (P < 0.001); and co-trimoxazole, 34.5% versus 58.7% (P = 0.003). The site of acquisition, recurrent UTIs, and previous antibiotic use were independent risk factors for antimicrobial resistance. Relapse rates were significantly higher when definitive antimicrobial treatment was not adequate (37.1% versus 9.3% when definitive antimicrobial treatment was adequate; P < 0.001). Our study reflects the rise of resistance to commonly used antibiotics in acute pyelonephritis. In order to choose the adequate empirical antibiotic therapy, risk factors for resistance should be considered.

Aggregatibacter actinomycetemcomitans osteomyelitis in a 12 year old boy: case report emphasizing the importance of tissue culture, and review of literature.

BACKGROUND: Aggregatibacter actinomycetemcomitans most commonly causes periodontitis but has been reported to infect heart valves, soft tissue, brain and lungs, and distal bones. Osteomyelitis distal to the jaw is rarely described. CASE PRESENTATION: We report an unusual and rare case of chronic osteomyelitis caused by A. actinomycetemcomitans in the toe of a paediatric patient, and review the available literature. The infection was managed with intravenous antibiotics followed by oral antibiotics. CONCLUSION: This is an unusual presentation of A. actinomycetemcomitans causing chronic osteomyelitis presumed due to nidation in a minimally damaged bone, associated with bacteraemia of an oral commensal. It occurred in the toe, without obvious dental predisposition; associated with minimal clinical disturbance and with muted immune response.

Método rápido para la detección de la sensibilidad a cefotaxima en enterobacterias / Rapid test for detection of susceptibility to cefotaxime in Enterobacteriaceae

En este trabajo se evalúa una prueba rápida in house para la detección de enterobacterias sensibles a cefotaxima, basada en el cambio de pH del rojo fenol debido a la hidrólisis de este antibiótico. Las cepas de enterobacterias procedentes de 1.947 urocultivos se evaluaron mediante los paneles MicroScan y esta prueba in house. Mediante los paneles de MicroScan se estudiaron 499 aislados de enterobacterias, entre los cuales había 27 aislados de Escherichia coli productora de β-lactamasa de espectro extendido (BLEE), 16 de Klebsiella pneumoniae BLEE y una de Klebsiella oxytoca BLEE. La prueba in house mostró una sensibilidad del 98% y una especificidad del 97%, con un valor predictivo negativo del 100% y un valor predictivo positivo del 78%. La prueba in house basada en el cambio de pH es útil en nuestro medio para detectar presuntivamente de forma rápida cepas de enterobacterias con cierta resistencia a cefotaxima.

In this work an "in house" rapid test based on the change in pH that is due to hydrolysis for detecting Enterobacteriaceae susceptible to cefotaxime is evaluated. The strains of Enterobacteriaceae from 1947 urine cultures were assessed using MicroScan panels and the "in house" test. This rapid test includes red phenol solution and cefotaxime. Using MicroScan panels, 499 Enterobacteriaceae isolates were evaluated, which included 27 isolates of Escherichia coli producing extended-spectrum beta-lactamases (ESBL), 16 isolates of Klebsiella pneumoniae ESBL and 1 isolate of Klebsiella oxytoca ESBL. The "in house" test offers the following values: sensitivity 98% and specificity 97%, with negative predictive value 100% and positive predictive value 78%. The "in house" test based on the change of pH is useful in our area for detecting presumptively cefotaxime-resistant Enterobacteriaceae strains.

Neonate with Mycoplasma hominis meningoencephalitis given moxifloxacin.

Mycoplasma hominis is a commensal organism in the genitourinary tract that can cause life-threatening CNS infections in neonates after intrauterine infection or through vertical transmission during birth. We present a case of an 11-day-old neonate presenting with fever and supporting laboratory evidence of a CNS infection. No systemic maternal infection or maternal genitourinary tract infection occurred at the time of delivery. Empirical treatment was initiated, consisting of amoxicillin, cefotaxime, and aciclovir. After clinical deterioration, 16S ribosomal DNA PCR in cerebrospinal fluid detected M hominis, antibiotic treatment was switched to moxifloxacin, and pharmacokinetic data were obtained. This Grand Round illustrates the challenges that exist in the diagnosis and treatment of M hominis meningoencephalitis: bacterial cultures are often negative and recommended empirical antimicrobials do not provide adequate antimicrobial coverage. Optimal antimicrobial treatment regimens for M hominis meningoencephalitis are unknown. Although we describe successful treatment of a neonate with a complicated M hominis meningoencephalitis with moxifloxacin, caution with fluoroquinolone monotherapy (including moxifloxacin) has to be taken into account because resistance to fluoroquinolones has previously been described.

An antimicrobial stewardship program reduces antimicrobial therapy duration and hospital stay in surgical wards / Un programa de uso de antimicrobianos reduce la duración de la terapia antimicrobiana y la estancia hospitalaria en salas de cirugía

We report a quasi-experimental study of the implementation of an antimicrobial stewardship program in two surgical wards, with a pre-intervention period with just assessment of prescription and an intervention period with a prospective audit on antibiotic prescription model. There was a significant reduction of length of stay and the total days of antimicrobial administration. There were no differences in mortality between groups. The antimicrobial stewardship program led to the early detection of inappropriate empirical antibiotic treatment and was associated with a significant reduction in length of stay and the total duration of antimicrobial therapy (AU)

Presentamos un estudio cuasi-experimental de la aplicación de un programa de uso de terapia antimicrobiana en dos salas quirúrgicas, con un período de pre-intervención en que se realizó evaluación de la prescripción y un período de intervención con una auditoría prospectiva sobre la prescripción antibiótica siguiendo un modelo de recomendación. Hubo una reducción significativa de la estancia media y del total de días de tratamiento antibiótico. No hubo diferencias en la mortalidad entre los grupos. El programa de uso de terapia antimicrobiana condujo a la detección precoz de tratamiento antibiótico empírico inadecuado y se asoció con una reducción significativa de la estancia media y la duración total de la terapia antimicrobiana (AU)

Empirical third-generation cephalosporin therapy for adults with community-onset Enterobacteriaceae bacteraemia: Impact of revised CLSI breakpoints.

Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. Clinical information was collected from medical records and CTX MICs were determined using the broth microdilution method. Eligible patients (n=409) were categorised into de-escalation (260; 63.6%), no switch (115; 28.1%) and escalation (34; 8.3%) groups according to the type of definitive antibiotics. Multivariate regression revealed five independent predictors of 28-day mortality: fatal co-morbidities based on McCabe classification [odds ratio (OR)=19.96; P<0.001]; high Pitt bacteraemia score (≥4) at bacteraemia onset (OR=13.91; P<0.001); bacteraemia because of pneumonia (OR=5.45; P=0.007); de-escalation after empirical therapy (OR=0.28; P=0.03); and isolates with a CTX MIC≤1mg/L (OR=0.17; P=0.02). Of note, isolates with a CTX MIC≤8mg/L (indicated as susceptible by previous CLSI breakpoints) were not associated with mortality. Furthermore, clinical failure and 28-day mortality rates had a tendency to increase with increasing CTX MIC (γ=1.00; P=0.01). Conclusively, focusing on patients with community-onset Enterobacteriaceae bacteraemia receiving empirical 3GC therapy, the present study provides clinically critical evidence to validate the proposed reduction in the susceptibility breakpoint of CTX to MIC≤1mg/L.

Microbiological Characteristics of Unresolved Acute Uncomplicated Cystitis.

This study sought to compare the antimicrobial susceptibility rates between acute uncomplicated cystitis patients with failed initial antimicrobial treatment, who were considered unresolved cases, and newly presenting acute uncomplicated cystitis patients without recent antimicrobial use within 3 months and to determine whether different treatment strategies should be applied according to recent antimicrobial exposure (RAE). Female acute uncomplicated cystitis patients with Escherichia coli growth, who visited our hospital's urology department from 2010 to 2014, were divided according to RAE. The antimicrobial susceptibility of E. coli was compared between the group with RAE and the group with no antimicrobial exposure (NAE) within 3 months. The total number of acute uncomplicated cystitis patients with E. coli growth was 259: 40 patients comprised the RAE group and 219 patients formed the NAE group. The mean age was significantly older and previous recurrent cystitis history was higher in the RAE group (p < 0.05). Furthermore, the antimicrobial susceptibility of E. coli to amoxicillin-clavulanic acid, cefotaxime, cefoxitin, ciprofloxacin, and trimethoprim-sulfamethoxazole was significantly lower in the RAE group, with susceptibility results of 64.7%/88.0% (RAE/NAE), 77.5%/89.0%, 79.4%/95.3%, 31.3%/64.2%, and 42.5%/70.6%, respectively. RAE was an independent factor for antimicrobial resistance. This study showed that antimicrobial susceptibilities were significantly lower in acute uncomplicated cystitis patients with failed initial antimicrobial treatment, who are defined as unresolved cases. Our results suggest that first-line antimicrobials might show poor efficacy in cases of unresolved, acute uncomplicated cystitis and alternative or secondary antimicrobials should be considered in these cases.

Nontyphoidal Salmonella septic arthritis of the elbow in a healthy infant.

A case of rarely encountered nontyphoidal Salmonella septic arthritis of the elbow in an infant with no preexisting disease is reported. Salmonella etiology was not suspected in this case, and the diagnosis was made only after bacterial isolation. Aspiration of the infected joint with radiological guidance initially failed to give a good clinical response. Arthrotomy was done with intravenous cefotaxime for 4 weeks followed by 2 weeks oral ciprofloxacin therapy to which the child responded favorably. Up to our knowledge this is the first case of nontyphoidal salmonella elbow septic arthritis in an infant in Saudi Arabia to be reported in the English literature.