Microbiological Clearance Research Articles

Clinical Course of Children with Chronic Suppurative Lung Disease or Bronchiectasis Infected with Pseudomonas aeruginosa.

Children with chronic wet cough and without cystic fibrosis (non-CF) may suffer from chronic suppurative lung disease (CSLD) or bronchiectasis. Pseudomonas aeruginosa (Pa) can be one of the offending microbes in these children. The present study aimed to describe the clinical course of children with the above two conditions who were infected with Pa. Data of 54 children with CSLD/bronchiectasis who were diagnosed and attended in our department were retrospectively analysed through a Cox proportional hazard model, with age, presence of bronchiectasis, use of inhaled colistin, azithromycin, inhaled hypertonic saline as the covariates. In 42 of the 54 patients, there was no identifiable cause or underlying chronic disorder. Microbiological clearance was defined as the absence of daily wet cough for four months along with four negative cultures taken during the last four consecutive follow-up visits. Multivariate analysis was performed with a Cox proportional hazard model with time to microbiological clearance as the outcome. Results are described as Hazard Ratios (HR) with 95% Confidence Intervals (95%CI). Nebulised antibiotics and the presence of bronchiectasis were statistically significant predictors of remission (HR: 3.99; 95%CI: 1.12-14.14; p = 0.032, and HR: 0.24; 95%CI: 0.08-0.71; p = 0.010). In conclusion, the rate of microbiological clearance increases with the use of inhaled colistin and decreases when there is established bronchiectasis.

Model-Informed Rationale for Early Therapeutic Drug Monitoring of Colistin in Critically Ill Patients.

Adequate colistin exposure is important for microbiological clearance. This study was performed in critically ill patients >18 years old to develop a simplified nonparametric pharmacokinetic (PK) model of colistin for routine clinical use and to determine the role of dose optimization. The Non-Parametric Adaptive Grid algorithm within the Pmetrics software package for R was used to develop a PK model from 47 patients, and external validation of the final model was performed in 13 patients. A 1-compartment multiplicative gamma error model with 0-order input and first-order elimination of colistin was developed with creatinine clearance and serum albumin as covariates on elimination rate constant. An R2 for observed vs individual predicted colistin concentrations of 0.92 was obtained in the validation cohort. High interindividual variability in colistin steady-state area under the plasma concentration-time curve (AUC) from from 120 hours to 144 hours (coefficient of variation=80.1%) and a high interoccasion variability (median coefficient of variation of AUC from time 0 to hours predicted every 8hours for initial 96hours after starting colistin=23.8) was predicted in patients who received this antibiotic for a period of over 152hours (n=22). With the model-suggested dose regimen, only 20% of simulated profiles achieved AUC from time 0 to 24 hours in the range of 50 to 60mg• h/L due to high variability in population PK. In this group of patients, steady-state colistin concentrations were predicted to be achieved >96hours after initiation of colistimethate sodium. This study advocates the need for early and repeated therapeutic drug monitoring and dose optimization in critically ill patients to achieve adequate therapeutic concentration of colistin.

Raoultella Species Associated Sepsis in Children: A Case Series at a Tertiary Hospital, Karachi

To determine the clinical outcome and management options of gram-negative Raoultella species reported at a tertiary care pediatric Hospital in Karachi. Descriptive study. Pediatric and child Health department of The Aga Khan University Hospital from January 2017 to June 2020. A retrospective chart review was done. Data was extracted for 20 patients with culture-positive Raoultella species. Study variables included demographic features, infection site, antibiotic sensitivities, Hospital duration, clinical outcome, and management options. Data were summarised using descriptive statistics and Kaplan-Meier plots using SPSS version 22. A total of twenty-three site cultures positive with Raoultella species were isolated among 20 children with a wide array of clinical symptoms and disease severity. Predominantly the organism was isolated in blood with 12 positive cultures (60%). Eleven (55%) of the patients were females having a median age of 9.5 months. Multidrug-resistant (MDR) and extensively drug-resistant species (XDR) were isolated from eleven (47.8%) and ten (43.5%) culture sites respectively. Combination therapy of colistin or fosfomycin with carbapenem and tigecycline (triple regimen) was used in seven (35%) patients with severe sepsis. Microbiological clearance (sterility) was achieved in twelve (60%) children. Eight children (40%) died of MDR/XDR Raoultella associated sepsis. Highly resistant Raoultella species were associated with high mortality among reported cases, with a limited choice of antibiotics and combination therapy. The management of Raoultella species is required with a multi-specialty approach. Furthermore, strict antimicrobial stewardship measures are required to control an outbreak of MDR and XDR infections in Pakistan. Raoultella species, Enterobacteriaceae, Children, Multidrug-resistant, Antimicrobial resistance.

Çoklu İlaca Dirençli Gram-negatif Bakteriyel Enfeksiyonların Tedavisinde Yükleme Dozlu veya Yüklemesiz Kolistin Tedavisinin Etkinliğinin Değerlendirilmesi

Aim: Colistin (Col) is an agent used in the treatment of multidrug-resistant gram-negative (MDRGN) bacterial infections. This drug has been administered with a loading dose in recent years to provide rapid clinical response and therapeutic blood levels. In our study, we aimed to evaluate whether there is a relationship between the efficacy of the loading dose of Col treatment, mortality, microbiological clearance during treatment, nephrotoxicity, and neurotoxicity side effects for the treatment of MDRGN bacterial infections. Material method: In this retrospective study, which included a control group, 6-years data was analyzed. Totally, 323 patients who received Col treatment with or without loading dose (LD) were included in the study. Patients were divided into two groups; I: without Col-LD regimen (those who were hospitalized in 2011-2014), II: with Col-LD regimen (those who were hospitalized in 2015-2017). Demographic characteristics such as age, gender, microbiological cultures, laboratory results, side effects, and mortality of the patients were evaluated. Results: A statistically significant relationship was found between with Col-LD regimen and nephrotoxicity. However, it was determined that there was no statistically significant relationship between microbiological clearance without a Col-LD regimen. Nephrotoxicity was found to be decreased with the Col-LD regimen. Neurotoxicity was observed more frequently (3.7%) in with Col-LD regimen. Initial and final C-reactive protein (CRP) and procalcitonin (PCT) levels were statistically significantly lower in with Col-LD regimen. Conclusion: It was found that with Col-LD regimen had a statistically significant effect on nephrotoxicity, neurotoxicity, and treatment outcome, but had no effect on microbiological clearance. In addition, with Col-LD regimen was effective in decreasing CRP and PCT values.

Lessons learned from the investigation and management of an outbreak of Shigella flexneri associated with a restaurant in London, 2019–2020

BackgroundFoodborne outbreaks of Shigella flexneri infection are uncommon in the UK. In November 2019, the United Kingdom Health Security Agency investigated an outbreak of S. flexneri associated with a fast-food restaurant in London. MethodsEpidemiological investigations included case ascertainment and interviewing suspected cases using enhanced surveillance questionnaires. Whole-genome sequencing (WGS) was used for characterisation of human isolates. Environmental investigations included a review of food safety processes at the implicated restaurant, administration of exposure questionnaires and stool sampling of staff. ResultsBetween November 2019 and February 2020, 17 cases were confirmed as part of the outbreak by WGS in London. Among these, 15 were linked to the implicated restaurant. A review of the food safety processes at the restaurant was satisfactory. Despite initial suboptimal coverage of stool screening of staff, all staff members working at the restaurant during the sampling period were screened and an asymptomatic food handler tested positive for S.flexneri with the outbreak WGS profile. The individual underwent microbiological clearance, and no further cases were reported. It was not possible to confirm the direction of transmission for the community cases or the staff member. ConclusionWe report an outbreak of S. flexneri in a fast-food restaurant in London with previous inspection ratings indicating good compliance with food safety and hygiene standards. WGS was crucial in identifying cases linked to the outbreak. This outbreak highlights the importance of prompt testing of food handlers in outbreaks suspected to be associated with food businesses.

Evaluation of central line salvage for mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) management practices in patients with hematologic malignancies

Patients with underlying hematologic malignancy (HM) and/or allogeneic hematopoietic stem cell transplant (HCT) recipients are at risk for mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) secondary to bacterial translocation. There is sparse data comparing MBI-LCBI management practices, in particular central venous catheter (CVC) salvage versus removal. We created a 22-item poll of Infectious Disease specialists at major US cancer centers on management controversies. Response rate was 44% (31/70). CVC salvage was a common practice among 87.5%. This was followed by a single center retrospective study (2017–2019) comparing outcomes related to CVC practices. We identified 115 patients, 52% (60/115) admitted for chemotherapy and 33% (38/115) for allogeneic HCT. The majority of patients (78%, 90/115) had their CVC removed. There was no difference in 72 h defervescence, microbiological clearance, in-hospital mortality, and 90-day recurrent infection between CVC salvage versus removal. CVC salvage is a safe approach in certain clinical scenarios.

Aminoglycoside or Polymyxin Monotherapy for Treating Complicated Urinary Tract Infections Caused by Extensively Drug-Resistant Pseudomonas aeruginosa: A Propensity Score-Adjusted and Matched Cohort Study.

IntroductionExtensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) infections are difficult to treat. We aimed to compare aminoglycosides or polymyxin monotherapy versus other antibiotic regimens (carbapenems, aztreonam, ceftazidime, cefepime, ceftolozane-tazobactam, or ceftazidime-avibactam) in complicated urinary tract infections (cUTI) caused by XDR-PA.MethodsStudy performed at a tertiary-care hospital from 2010 to 2019. All consecutive adult patients with XDR-PA urine cultures and diagnosed with cUTI were retrospectively reviewed. XDR phenotype was defined according to Magiorakos et al. A propensity score was used as a covariate in multivariate analyses and for matching. Primary outcome was early clinical failure and at end of treatment (EOT). Main secondary outcomes were 30- and 90-day mortality, microbiological clearance, and antibiotic-related side effects.ResultsOf the 465 episodes screened, 101 were included, 48% were treated with aminoglycoside or colistin monotherapy. Most XDR-PA were susceptible to colistin (100%) and amikacin (43%). Patients treated with antibiotic regimens other than aminoglycosides or polymyxin monotherapy were more likely to have hematologic malignancy (p < 0.001), higher SOFA score (p = 0.048), and bacteremia (p = 0.003). In multivariate models adjusted by propensity score, aminoglycoside or colistin monotherapy was not associated with worse outcomes. After propensity score matching, 28 episodes in each treatment group were matched. Adjusted ORs (95% CI) for early clinical failure and at EOT with aminoglycosides or polymyxin monotherapy were 0.53 (0.18–1.58) and 1.29 (0.34–4.83), respectively. Aminoglycoside or colistin monotherapy was not associated with higher 30-day (HR 0.93, 95% CI 0.17–5.08) or 90-day mortality (HR 0.68, 95% CI 0.20–2.31), nor with absence of microbiological clearance (OR 0.72, 95% CI 0.33–1.58). No statistically significant differences were found in terms of nephrotoxicity. Clostridioides difficile infection was observed only in the “other antibiotic regimens” group (n = 6, 11.3%).ConclusionsAminoglycosides or polymyxin monotherapy showed good efficacy and safety profile in treating cUTI caused by XDR-PA. These results may be useful for antibiotic stewardship activities.Electronic Supplementary MaterialThe online version of this article (10.1007/s40121-021-00570-z) contains supplementary material, which is available to authorized users.

Antibiotic Prophylaxis Prior to Urodynamic Study in Patients with Neurogenic Bladder and Asymptomatic Bacteriuria: A Randomized Controlled Trial

Background: Symptomatic urinary tract infection (UTI) is a common complication after urodynamic study (UDS). While the role of antibiotic prophylaxis before UDS is controversial. Objective: To compare the incidence rate of symptomatic UTI after UDS in patients with and without antibiotic prophylaxis. Materials and Methods: We conducted a randomized, open-label, noninferiority controlled trial in adults with asymptomatic bacteriuria who were undergoing UDS. The participants were randomly assigned (1:1) to receive either gentamicin 5 mg/kg plus ampicillin 1-gram intravenous (IV) infusion 1 hour before UDS or no prophylaxis. The primary outcome was an incidence rate of symptomatic UTI within 48 hours after UDS. Secondary outcomes were adverse effects and microbiological clearance of urine at 48 hours after UDS. The study was terminated early after the first interim analysis due to safety concerns. Results: 26 patients were enrolled, median age was 52 years (range, 25 to 75 years), 69.2% were male, and all had a neurogenic bladder as indication for UDS. Of these, 13 patients each were allocated to the antibiotic prophylaxis group and the non-antibiotic prophylaxis group. In the antibiotic prophylaxis group, 12/13 (92.3%) received gentamicin plus ampicillin and one received ceftriaxone. The incidence rate of symptomatic UTI after UDS was significantly higher in patients with no antibiotic prophylaxis (5/13; 38.5%) than those who received antibiotic prophylaxis (0%) (p=0.04). No adverse drug events were observed. The microbiological clearance in urine at 48 hours after UDS was significantly higher in patients who received antibiotic prophylaxis (8/11; 72.7%) compared to those without antibiotic prophylaxis (0/13; 0%) (p&lt;0.001). Conclusion: Antibiotic prophylaxis reduced the incidence of symptomatic UTI in patients with neurogenic bladder and asymptomatic bacteriuria who were undergoing UDS. A single-dose of antibiotics within an hour prior to UDS seems to be a proper option. Keywords: Antibiotic prophylaxis; Asymptomatic bacteriuria; Urodynamic study

Factors Associated with Microbiological Outcomes to Colistin in Patients with Multidrug-resistant Gram-Negative Bacterial Infections

Background: Multidrug-resistant (MDR) gram-negative bacterial infections continuously increases in prevalence, rate of ICU admission and mortality. Although, colistin has been used to treat MDR organisms, the controversial outcomes regarding its efficacy and safety were reported. Therefore, factors related with microbiological response to colistin should be determined. Objective: To evaluate the rate and related factors of microbiological outcome in patients who received intravenous colistin for treatment of MDR gram-negative bacterial infections. Materials and Methods: The retrospective cohort study was performed in adult patients between June 2015 and June 2017. Patient information, microbiology data, duration of colistin treatment and clinical outcomes were reviewed and analyzed. Microbiological responses were classified as either eradication or persistence of the initial MDR bacteria. Factors influencing microbiological response were determined by multiple logistic regression analysis. Results: 303 colistin-given patients were enrolled with the mean age of 62.8&plusmn;18.3 years. Pneumonia and soft tissue infections were the most two common sites of infection. Reports of culture revealed monomicrobial gram-negative bacteria 80.5%. Acinetobacter baumannii and Pseudomonas aeruginosa were the major organisms accounting for 79.9% and 17.2%, respectively. Microbiological clearance rate of colistin was 66%. Multivariate analysis demonstrated the factors related with poor microbiological response were (a) AKI before colistin treatment associated with higher severity of AKI (b) presence of pneumonia, (c) infection with P. aeruginosa and (d) mixed gram-negative bacterial infections. The overall mortality rate was 39.3% with no significant differences of mortality rate and incidence of AKI after colistin administration between the eradication and persistence groups. Conclusion: Colistin accomplished with rather good microbiological response in clearance of MDR gram-negative bacteria. AKI influenced the microbiological response therefore early and aggressive care to prevent AKI is mandatory. Additionally, because of high non-response rate in P. aeruginosa infection, combined antibiotics and surveillance may be crucial. Keywords: Colistin; Microbiological response; Factors for good and poor outcomes

Combination antibiotic therapy versus monotherapy in the treatment of acute exacerbations of chronic obstructive pulmonary disease: an open-label randomized trial

BackgroundThe role of antibiotics in the treatment of chronic obstructive pulmonary disease (COPD) exacerbations and their effectiveness in combination have not been clearly established. To determine whether using a combination of fluoroquinolones and beta-lactams improves the clinical and microbiological efficacy of antibiotics on day 20 of treatment, we conducted an open-label randomized trial based on clinical outcomes, microbiological clearance, spirometry tests, and signs of systemic inflammation in patients hospitalized with acute exacerbations of COPD.MethodsWe enrolled 139 subjects with COPD exacerbations, defined as acute worsening of respiratory symptoms leading to additional treatment. Patients were divided randomly into two groups: 79 patients using beta-lactam antibiotics alone and 60 using beta-lactam antibiotics plus fluoroquinolones. Clinical and microbiological responses, spirometry tests, symptom scores, and serum C-reactive protein (CRP) levels were evaluated.ResultsClinical success, lung function, and symptoms were similar in patients with or without fluoroquinolone administration on days 10 and 20. Combination therapy was superior in terms of microbiological outcomes and reduction in serum CRP value. Although equivalent to monotherapy in terms of clinical success, the combination showed superiority in terms of microbiological success and a decrease in CRP. The combination therapy group had a higher microbiological success rate with gram-negative bacteria than the monotherapy group with Pseudomonas aeruginosa (100% vs. 33.3%, respectively) and Acinetobacter baumanii (100% vs. 20%, respectively) (P < 0.05).ConclusionsConcomitant use of fluoroquinolone and beta-lactam antibiotics for bacterial infections during COPD exacerbations caused by gram-negative bacteria appear to be effective and should be applied in clinical practice.

Safety and efficacy of colistin and fluoroquinolone in neonatal persistent late-onset sepsis

Growing resistance of microorganisms to antibiotics for the treatment of late-onset sepsis (LOS) in premature infants has led physicians to use antibiotics that are not well studied in neonatal populations. We aimed to determine the efficacy and safety of colistin and fluoroquinolone for the treatment of persistent LOS. We retrospectively reviewed infants with gram-negative LOS, who received either colistin or fluoroquinolone therapy, to determine if there was a significant difference in kidney and liver function tests and electrolyte levels before, during, and at the end of the treatment. Infants who received colistin and fluoroquinolone had 17 and 34 positive cultures with gram-negative organisms, respectively. Multi-drug resistant organisms were more common in infants who received colistin than in those who received fluoroquinolone. Microbiological clearance was found to be higher in infants treated with fluoroquinolone than in those treated with colistin. In both the groups, the median levels of kidney and liver function tests and electrolytes showed a significant increase during the treatment. The prescription of colistin and fluoroquinolones should be reserved for cases with no other safe and effective alternatives.

Time to resolution of genital symptoms for uncomplicated gonorrhoea: a prospective cohort study

ObjectivesTo determine the time to resolution of symptoms (TTR) following treatment of uncomplicated gonorrhoea and to identify factors associated with TTR in a cohort of sexual health clinic attendees.MethodsParticipants were...

Amikacin for the treatment of carbapenem-resistant Klebsiella pneumoniae infections: clinical efficacy and toxicity

Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) are an increasing global threat with limited therapeutic options. Our objective was to evaluate clinical and microbiological outcomes of patients treated with amikacin for CRKp infections. We did a retrospective cohort of patients > 18years old, with CRKp infections treated with amikacin in two tertiary care hospitals in Porto Alegre, Brazil. The impact of clinical factors, antibiotic treatment, and amikacin minimum inhibitory concentration (MIC) on patients' 30-day mortality was assessed. Microbiological clearance and nephrotoxicity (assessed by RIFLE score) were evaluated as secondary outcomes. A Cox regression analysis was done for mortality. We included 84 patients for analysis. Twenty-nine (34.5%) patients died in 30days. Amikacin MIC values ranged from 0.125 to 8μg/mL and did not influence on mortality, regardless of the prescribed dose of this antibiotic (P = 0.24). Bacterial clearance occurred in 17 (58.6%) of 29 patients who collected subsequent cultures. Two (16.6%) of the 12 persistently positive cultures changed the amikacin susceptibility profile from susceptible to intermediate. Twenty-nine (37.2%) patients developed acute kidney injury (AKI): risk 13, injury 11, and failure 5. Risk factors for AKI were higher baseline eGFR (P < 0.01) and combination therapy with colistin (P = 0.02). Comparing patients who received combination with colistin vs polymyxin B, AKI occurred in 60.0% vs 20.6%, respectively, P < 0.01. Fifteen of the 16 (16.6%) patients who developed renal injury or failure were receiving colistin. In conclusion, amikacin was an effective treatment for CRKp infections. Within susceptible range, amikacin MIC values did not influence on clinical outcomes. Combination therapy of amikacin and colistin was highly nephrotoxic and should be used with caution.

Clinical Outcomes for Telavancin for Salvage Therapy in Methicillin-resistant Staphylococcus Aureus Bacteremia

Background Little evidence exists for the use of telavancin in methicillin-resistant Staphylococcus aureus (MRSA) bacteremia as salvage therapy. This study aims to evaluate the efficacy and safety of telavancin as salvage therapy in the treatment of MRSA bacteremia. Methods Electronic medical charts of patients who received telavancin for the treatment of MRSA bacteremia at an academic, tertiary care medical center in the United States between January 1, 2015, and May 31, 2019, were reviewed for clinical cure, reinfection, prior antibiotic use, source of infection, microbiological culture clearance, patient mortality, and adverse effects. The primary outcome was clinical cure. Results Thirty-eight charts were identified, and 11 met inclusion criteria for this analysis. Vancomycin or daptomycin was given for an average of 5.4 and 2.6 days, respectively, before the initiation of telavancin. The average telavancin dose used was 7.5 mg/kg. All patients achieved clinical cure, and there were no instances of 60-day mortality. Two patients experienced reinfection: 1 patient after 268 days and another after 467 days. Four patients experienced either QTc prolongation or acute renal failure. Conclusions The use of telavancin in MRSA bacteremia demonstrated microbiological cure, clinical cure, and minimal reinfection in the reviewed patient population. Telavancin may be a potential treatment option for patients with MRSA bacteremia as salvage therapy.

Mortality and microbiological clearance among critically ill patients receiving Polymyxin B in a Malaysian ICU: A 10 years retrospective study

Background: In the era of increasing bacterial resistance, Polymyxins became the choice to treat infection by multidrug resistant organism. This study aimed to observe the microbiological outcome and all-cause mortality among patients receiving Polymyxin B (PolyB) in Intensive Care Unit (ICU). Methods and materials: In this retrospective observational study, patients who were prescribed PolyB were identified from the hospital electronic prescribing system. Only patients who were prescribed in ICU were included. Culture and sensitivity (C&S) before and after initiation of PolyB therapy was retrieved to determine microbiological clearance. Results: Since year 2008 to 2018, a total of 572 patients were prescribed PolyB. After excluding non-ICU cases and missing data, 31 patients were included. The median age of patients was 59 (5–68) y old and 15 (48.4%) were female. The comorbidities were hypertension (14, 45.2%), diabetes mellitus (11,35.5%) and/or dyslipidemia (9, 29%). Almost all patients (96.8%) were on inotropes. The length of ICU stay was median 20 (15–25) d. The average weight were 73.7 ± 21.8 kg with a median cumulative dose of 750 (385–1225)mg or average 2.2 ± 0.6 mg/kg/day, given intravenously for the median duration of 7 (4–12) d. The documented indications were pneumonia (15, 48.4%) and sepsis (14; 45.2%). Common infection sites were respiratory tract (16; 51.6%) and bloodstream (7; 22.6%). Among all the bacteria isolated in 28 cultures, Acinetobacter baumannii was the most common (25, 80.6%), followed by Pseudomonas aeruginosa (3, 9.7%). Minimum inhibitory concentration (MIC) were determined in 61.3% of cases and found to be ≤2 mg/L. Cultures were repeated in 21 cases which showed microbiological clearance in 14 (66.7%) patients but not in 7 patients (33.3%). During therapy, acute rise of serum creatinine was observed in 14 (45.2%) patients. Since the initiation of PolyB, 18 (58.1%) patients died during therapy. Overall, 21 patients (67.7%) died within 14 d and 29 patients (93.5%) died within 30 d. The commonest documented cause of death was septic shock (25; 83.3%). Conclusion: There was a high rate of mortality seen among patients receiving PolyB in ICU despite microbiological clearance in two thirds of patients. Further investigations and interventions are warranted to improve these outcomes.

Association of Ct Values from Real-Time PCR with Culture in Microbiological Clearance Samples for Shiga Toxin-Producing Escherichia coli (STEC).

Shiga toxin-producing Escherichia coli (STEC) are associated with acute gastroenteritis worldwide, which induces a high economic burden on both healthcare and individuals. Culture-independent diagnostic tests (CIDT) in frontline microbiology laboratories have been implemented in Alberta since 2019. The objectives of this study were to determine the association between gene detection and culture positivity over time using STEC microbiological clearance samples and also to establish the frequency of specimen submission. Both stx genes’ amplification by real-time PCR was performed with DNA extracted from stool samples using the easyMAG system. Stools were inoculated onto chromogenic agar for culture. An association between gene detection and culture positivity was found to be independent of which stx gene was present. CIDT can provide rapid reporting with less hands-on time and technical expertise. However, culture is still important for surveillance and early cluster detection. In addition, stool submissions could be reduced from daily to every 3–5 days until a sample is negative by culture.

Intravenous push versus intravenous piggyback beta-lactams for the empiric management of gram-negative bacteremia.

Nationwide shortages of small-volume parenteral solutions (SVPS) compelled hospitals to develop strategies including the use of intravenous push (IVP) administration of antibiotics to reserve SVPS for absolute necessities. It is unknown if administration of beta-lactam antibiotics (BL) via IVP results in worse clinical outcomes compared to intravenous piggyback (IVPB) due to the potential inability to achieve pharmacodynamic targets. Our health-system implemented a mandatory IVP action plan for BL from October 2017 to September 2018. This was a retrospective study of adult patients with GNB who received empiric therapy with IVPB (30minutes) or IVP (5minutes) cefepime (FEP) or meropenem (MEM) for at least 2days. Endpoints included clinical response, microbiological clearance and mortality. All data are presented as n (%) or median (interquartile range). The final cohort included 213 patients (IVPB n=105, IVP n=108). The primary source of bacteremia was urinary, with Escherichia coli being the primary pathogen. Escalation of therapy was similar between groups (15 [14%] vs 11 [10%], P=.36) at a median of 3days (P=.68). No significant differences were observed in any secondary endpoints including microbiological clearance, bacteremia recurrence, time to defervescence, WBC normalization, vasopressor duration or in-hospital mortality. Our findings suggest no differences in clinical response with the use of IVP compared to IVPB FEP and MEM for treatment of GNB. This form of administration may be considered as a fluid conservation strategy in times of shortage.

Experience With Ceftolozane-Tazobactam for the Treatment of Serious Pseudomonas aeruginosa Infections in Saudi Tertiary Care Center.

Introduction:Multidrug-resistant Pseudomonas aeruginosa isolates have multiple resistance mechanisms, and there are insufficient therapeutic options to target them. Ceftolozane-tazobactam is a novel antipseudomonal agent that contains a combination of an oxyimino-aminothiazolyl cephalosporin (ceftolozane) and a β-lactamase inhibitor (tazobactam).Methods:A single-center retrospective observational study between January 2017 and December 2018 for patients who had been diagnosed with carbapenem-resistant P aeruginosa infections and treated with ceftolozane-tazobactam for more than 72 hours. We assessed clinical success based on microbiological clearance as well as the clinical resolution of signs and symptoms of infection.Results:A total of 19 patients fit the inclusion criteria, with a median age was 57 years, and 53% were female. The types of infections were nosocomial pneumonia, acute bacterial skin, and skin structure infections; complicated intra-abdominal infections; and central line–associated bloodstream infections. All of the isolates were resistant to both meropenem and imipenem. The duration of therapy was variable (average of 14 days). At day 14 of starting ceftolozane-tazobactam, 18 of 19 patients had a resolution of signs and symptoms of the infection. Only 14 of 19 patients (74%) had proven microbiological eradication observed at the end of therapy. During therapy, there was no adverse event secondary to ceftolozane-tazobactam, and no Clostridium difficile infection was identified. The 30-day mortality rate was 21% (4/19).Conclusions:Multidrug-resistant P aeruginosa infection is associated with high mortality, which would potentially be improved using a new antibiotic such as ceftolozane-tazobactam. Studies are required to explain the role of combination therapy, define adequate dosing, and identify the proper duration of treatment.

Developing a core outcome set for children with protracted bacterial bronchitis.

BackgroundProtracted bacterial bronchitis (PBB) is a chronic endobrochial infection and a leading cause of chronic wet cough in children. There is an urgent need for a randomised controlled trial to investigate the optimal treatment but there is no core outcome set (COS) to inform choice of outcomes. A COS is a standardised set of outcomes representing the minimum that should be measured and reported in clinical trials of a specific condition. We have developed a COS for PBB.MethodsPotential core outcomes were collated from a systematic review, interviews with parents and a clinician survey. A two-round Delphi survey of healthcare professionals identified which outcomes had consensus for inclusion. The final COS was agreed at a consensus meeting of parent representatives and clinicians.Results20 outcomes were identified for the Delphi survey. After two rounds, 10 reached consensus. These were combined and edited at the consensus meeting into the final six: 1) Resolution of cough assessed using a cough score/diary recorded daily by parent(s) during treatment; 2) relapse of chronic wet cough and/or cumulative antibiotic treatment during ≥12 months follow-up; 3) change in child's quality of life (parent-proxy reporting for young children); 4) emergence of antibiotic resistance; 5) development of bronchiectasis diagnosed on clinically indicated computed tomography scans; and 6) microbiological clearance of identified respiratory pathogen if samples readily available.ConclusionsWe have developed a COS for PBB which will reduce the outcome heterogeneity and bias of future clinical trials, as well as promoting comparison between studies.

1596. Impact of Vancomycin Area Under Curve on Persistent Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections (BSI)

BackgroundPersistent Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with significant morbidity, mortality, and healthcare expenditures. Vancomycin (VAN) remains the treatment of choice for invasive MRSA BSI. Current guidelines for the treatment of MRSA BSI recommend a VAN AUC24h/MIC ratio ≥400. The Detroit Medical Center (DMC) implemented an AUC guided dosing strategy. However, data on the association between AUC24h and clinical outcomes in MRSA BSI are limited. We aimed to evaluate the association between VAN AUC24h and persistent bacteremia (PB) among patients with BSI.MethodsMulti-center, retrospective cohort study from January 2015 to November 2018. We included adult patients with MRSA bacteremia treated with VAN for which AUC24h monitoring was performed. AUC was measured using 2-level guided dosing. The primary outcome was PB defined as continued positive cultures >72 hours after VAN initiation. Classification and Regression Tree (CART) analysis was performed to determine the AUC24h breakpoint (BP) most predictive of PB in the cohort. Mann–Whitney and Fischer exact tests were used for univariate analysis. The independent association between AUC24h, dichotomized at the CART-derived cut-point, was then examined through multivariable logistic regression analysis.ResultsOverall, 137 patients were included. The median age was 59 (18–85) years, 69.3% male, and 75.2% African American predominance. Most common sources of BSI were skin/soft tissue (39.4%), pneumonia (25.5%), and osteoarticular (16.8%). The median APACHE II score was 13 (8–20). Median time to microbiological clearance was 2.5 days (0.5–12). Patients with AUC24h ≤ 406.25 were more likely to have PB compared with those with AUC24h > 406.25 (59.4% and 35.2%, respectively; P = 0.002). After controlling for age, intensive care stay, and concomitant β-lactam therapy; AUC of ≤ 406.25 (aOR 2.767, 95% CI 1.212–6.318) and endocarditis (aOR 2.87, 95% CI 1.079–7.638) were independently associated with PB.ConclusionVAN AUC24h BP of <406.25 was independently associated with PB in patients with MRSA BSI. Our findings underscore the importance of VAN dose optimization to achieve timely bacterial clearance in MRSA bacteremia.Disclosures All authors: No reported disclosures.