Intravenous Fluoroquinolone Research Articles

Right-Sided Endocarditis Secondary to Aeromonas hydrophila: A Case Report

Right-sided endocarditis represents a distinct clinical condition observed in individuals with a history of parenteral drug use or those with implanted pacemakers or other intracardiac devices. Aeromonas infections, although uncommon in humans, particularly endocarditis cases, are exceedingly rare. Here, we report the case of a 72-year-old female with a medical history of arterial hypertension and chronic kidney disease undergoing hemodialysis via a tunneled permanent central venous catheter. She presented with chills and a fever of 38.3°C. Physical examination revealed a grade 3 protosystolic murmur at the tricuspid focus. Blood cultures from central and peripheral sites yielded growth of Aeromonas hydrophila. Transthoracic echocardiography demonstrated a fusiform, semi-mobile vegetation measuring 16 x 15 mm at the outlet of the superior vena cava, suggestive of endocarditis. Intravenous fluoroquinolones were initiated based on antibiogram results, leading to resolution of imaging findings after a 21-day treatment course.

31. Stepwise Expansion of Antimicrobial Stewardship Program and Its Impact on Antibiotic Use and Resistance Rates in a Tertiary Care Hospital in Korea

BackgroundThe U.S. Centers for Disease Control and Prevention released the core elements of antimicrobial stewardship program (ASP). In some countries, however, they may be difficult to apply in countries with limited resources. In this study, we evaluated the impact of successful ASP implementation on antibiotic use and resistance rates in an institution with limited infrastructural support.MethodsA series of ASP activities were reviewed according to the core elements of ASP. The retrospective data of all hospitalized patients at a tertiary care teaching hospital was collected from January 2010 to December 2019, including antibiotic prescription data and culture results of all clinical specimens. The trends of the antibiotic-resistant rates were compared with nationwide data in Korea. The trend analyses were performed with 2-sided correlated seasonal Mann-Kendall nonparametric tests.ResultsThe ASP activities over the past decade were summarized in Table. After activities such as preauthorization were achieved, other ASP activities were added one by one. Also, the infectious disease pharmacists, as ASP co-leaders, mainly carried out the following activities: reducing redundant anti-anaerobic antimicrobials and intravenous fluoroquinolones, and advised the physicians to discontinue the antibiotic prescription in cases when the intervention was plausible. After the ASP implementation, total antibacterial use significantly decreased (P < 0.01; Figure). The use of glycopeptides (P < 0.01) and fluoroquinolones (P < 0.01) gradually decreased, while the use of third-generation cephalosporines did not significantly change (P=0.48). There was no significant change in total carbapenems use, but ertapenem use increased (P=0.02). Compared with the nationwide data, methicillin-resistant Staphylococcus aureus was on a decreasing trend consistently. Although third-generation cephalosporin-resistant Escherichia coli increased, third-generation cephalosporin resistant-Klebsiella pneumoniae and carbapenem resistant-Pseudomonas aeruginosa did not increase.Table. Antimicrobial stewardship activities for hospitalized patients over the past decade in Seoul National University Bundang Hospital. ASP: antimicrobial stewardship; ID: infectious disease; CDSS: Clinical decision support system Figure. DOT per 1,000 patient-days in Seoul National University Bundang Hospital and implemented actions of antimicrobial stewardship program. DOT: days of therapy; ID: infectious disease; PCR: polymerase chain reaction; GPC: gram positive cocci; Group 1 carbapenem: ertapenem ConclusionA stepwise implementation of the core ASP elements was effective in improving the appropriate use of antibiotics and reducing the antibiotic resistant organisms, even with limited human resources.Disclosures All Authors: No reported disclosures

101. Impact of an Integrated Tele-Antimicrobial Stewardship Program at a Rural Community Hospital

BackgroundSmall hospitals in the US may lack access to infectious diseases (ID) expertise despite similar rates of antimicrobial use and drug-resistant bacteria as larger hospitals. A tele-antimicrobial stewardship program (TASP) is a force multiplier, expanding access to specialty care, training, and guidance on appropriate resource utilization. Data on the impact of TASPs in community or rural inpatient settings is limited.MethodsWe established a TASP at a 160-bed hospital in Armstrong County, PA (population < 5000) in September 2020. Tele-ID consult services were already being used (Figure 1). A non-local ID pharmacist or ID physician performed prospective audits and provided feedback with 1 local pharmacist on a 30-minute video conference call daily. At TASP implementation, all patients receiving intravenous (IV) fluoroquinolones, metronidazole, and azithromycin were reviewed. Figure 1 shows the additional support following TASP implementation, including addition of ceftriaxone, carbapenems, IV vancomycin, and tocilizumab to daily reviews. A patient monitoring form was developed to track interventions and the local pharmacists were trained in documentation. Table 1 lists other TASP features implemented.Figure 1. TASP Timeline Table 1. TASP Accomplishments ResultsFrom 09/01/2020 to 04/30/2021, 304 stewardship opportunities were identified and 77% of interventions were accepted. Recommending a duration of therapy was accepted most frequently (93.5%) and de-escalation of therapy least frequently (69.6%) (Table 2). Recommending an ID consultation or diagnostic testing was always accepted but only comprised 6.2% of all interventions. Daily calls involved an average of 5 patient reviews. Monthly antimicrobial use declined on average from 673 DOT (days of therapy)/1000 PD (patient days) to 638 DOT/1000 PD (Figure 2). Daily calls were cancelled on 31/166 weekdays (18.7%) due to staffing shortages.Table 2. TASP Interventions (9/2020 - 4/2021) Figure 2. Monthly Antimicrobial Use in Days of Therapy (DOT) per 1000 Patient Days (4/2019 - 5/2021) ConclusionImplementation of TASP in a community hospital resulted in a high percentage of accepted stewardship interventions and lower antimicrobial usage. Success is dependent on robust educational efforts, establishing strong relationships with local providers, and involvement of key stakeholders. Lack of dedicated stewardship time for local pharmacists is a very significant barrier.Disclosures Erin K. McCreary, PharmD, BCPS, BCIDP, AbbVie (Consultant)Cidara (Consultant)Entasis (Consultant)Ferring (Consultant)Infectious Disease Connect, Inc (Other Financial or Material Support, Director of Stewardship Innovation)Merck (Consultant)Shionogi (Consultant)Summit (Consultant) Erin K. McCreary, PharmD, BCPS, BCIDP, AbbVie (Individual(s) Involved: Self): Consultant; Cidara (Individual(s) Involved: Self): Consultant; Entasis (Individual(s) Involved: Self): Consultant; Ferring (Individual(s) Involved: Self): Consultant; Infectious Disease Connect, Inc (Individual(s) Involved: Self): Director of Stewardship Innovation, Other Financial or Material Support; Merck (Individual(s) Involved: Self): Consultant; Shionogi (Individual(s) Involved: Self): Consultant; Summit (Individual(s) Involved: Self): Consultant Tina Khadem, PharmD, Infectious Disease Connect, Inc. (Employee) Nancy Zimmerman, RN, BSN, I’d connect (Employee) John Mellors, MD, Abound Bio, Inc. (Shareholder)Accelevir (Consultant)Co-Crystal Pharma, Inc. (Other Financial or Material Support, Share Options)Gilead Sciences, Inc. (Advisor or Review Panel member, Research Grant or Support)Infectious DIseases Connect (Other Financial or Material Support, Share Options)Janssen (Consultant)Merck (Consultant) Rima Abdel-Massih, MD, Infectious Disease Connect (Employee, Director of Clinical Operations) Rima Abdel-Massih, MD, Infectious Disease Connect (Individual(s) Involved: Self): Chief Medical Officer, Other Financial or Material Support, Other Financial or Material Support, Shareholder J Ryan. Bariola, MD, Infectious Disease Connect (Other Financial or Material Support, salary support)

Management of initial colonisations with Burkholderia species in France, with retrospective analysis in five cystic fibrosis Centres: a pilot study

BackgroundWhereas Burkholderia infections are recognized to impair prognosis in cystic fibrosis (CF) patients, there is no recommendation to date for early eradication therapy. The aim of our study was to analyse the current management of initial colonisations with Burkholderia cepacia complex (BCC) or B. gladioli in French CF Centres and its impact on bacterial clearance and clinical outcome.MethodsWe performed a retrospective review of the primary colonisations (PC), defined as newly positive sputum cultures, observed between 2010 and 2018 in five CF Centres. Treatment regimens, microbiological and clinical data were collected.ResultsSeventeen patients (14 with BCC, and 3 with B. gladioli) were included. Eradication therapy, using heterogeneous combinations of intravenous, oral or nebulised antibiotics, was attempted in 11 patients. Six out of the 11 treated patients, and 4 out of the 6 untreated patients cleared the bacterium. Though not statistically significant, higher forced expiratory volume in 1 second and forced vital capacity at PC and consistency of treatment with in vitro antibiotic susceptibility tended to be associated with eradication. The management of PC was shown to be heterogeneous, thus impairing the statistical power of our study. Large prospective studies are needed to define whom to treat, when, and how.ConclusionsPending these studies, we propose, due to possible spontaneous clearance, to check the presence of Burkholderia 1 month after PC before starting antibiotics, at least in the milder cases, and to evaluate a combination of intravenous beta-lactam + oral or intravenous fluoroquinolone + inhaled aminoglycoside.

Delafloxacin: a novel fluoroquinolone with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa

ABSTRACTIntroduction: The resistance to current antimicrobial agents, including fluoroquinolones, has continued to grow among various pathogens indicating a need for new antimicrobials to combat multi-drug resistant (MDR) organisms. In June 2017, delafloxacin received approval by the US Food and Drug Administration for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) in adults caused by designated susceptible bacteria.Areas covered: This review describes the pharmacology, pharmacodynamics, pharmacokinetics, product information, efficacy, and safety of delafloxacin.Expert commentary: Delafloxacin is a novel oral and intravenous fluoroquinolone with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, offering a new option for the treatment of ABSSSI and potentially for complicated urinary tract infections and severe community-acquired bacterial pneumonia.

Necrotizing Clostridium difficile Enteritis Complicating Fulminant Colitis

Background:Clostridium difficile infections result from an imbalance in normal bacterial flora, allowing C. difficile bacteria overgrowth. Whereas such bacterial overgrowth is typically confined to the colon, there have been reports of an increasing prevalence of C. difficile infections involving the small bowel, with the majority of patients presenting with a history of partial or total colectomy. We present two rare cases of necrotizing C. difficile enteritis complicating fulminant C. difficile colitis. Case Presentations: A 74-year-old male presented with a two-week history of watery diarrhea and escalating abdominal pain without recent antibiotic use. Work-up was significant for leukocytosis, bandemia, lactic acidosis, and elevated creatinine. Initial diagnosis of C. difficile was treated with intravenous fluoroquinolone and metronidazole. He deteriorated and a total colectomy with small bowel resection was performed. Final pathology revealed pseudomembranous colitis with focal mucosal ischemia and pseudomembranous necrotizing enteritis. Post-operatively the patient's condition fluctuated, requiring re-initiation of antibiotics and vasopressor therapy; he ultimately recovered. A 72-year-old female presented with severe abdominal pain and septic shock two weeks after total abdominal colectomy with end ileostomy for severe C. difficile colitis. An exploratory laparotomy appeared normal, without an identifiable pathology source. Post-operatively she required vasopressor support and mechanical ventilation. She received intravenous metronidazole and vancomycin enemas. Clostridium difficile assays confirmed the diagnosis of relapsed pseudomembranous enteritis. Antibiotic therapy continued without further incident. Conclusion:Clostridium difficile enteritis presents a unique challenge because of its difficulty in diagnosis, a fact underscored by the high morbidity and mortality of small bowel of C. difficile infections. Clostridium difficile enteritis should be suspected in patients not improving after recent colectomy for C. difficile colitis. Continuation of antibiotics and total colectomy should be considered in patients with un-explained acute intra-abdominal pathology or persistent sepsis after colectomy for fulminant C. difficile colitis.

Impact of Intervention by an Antimicrobial Stewardship Team on Conversion from Intravenous to Oral Fluoroquinolones

BackgroundEarly conversion from intravenous to oral antibiotics plays an important role in lowering the risk of catheter-associated infections, reducing the workload of nurses, decreasing direct and indirect costs, and shortening hospital stays. In August 2015, an antimicrobial stewardship program (ASP) was implemented to facilitate conversion from intravenous to oral administration of fluoroquinolones in our institute. This study evaluated the clinical and economic impact of the intervention.Materials and MethodsData were retrospectively collected by reviewing electronic medical records. All hospitalized patients aged 18 and older who met the study inclusion criteria for the conversion were included between August and November 2015. We computed the physicians' adherence rate to the ASP recommendations. We also measured the total use of fluoroquinolones, length of hospital stay, and medication costs.ResultsDuring 4 months, 129 cases were enrolled in the study. The adherence rate was 79.8%. The average total prescription volume of intravenous fluoroquinolones, the length of hospital stay, and the total cost of the fluoroquinolones statistically significantly decreased in the intervention-adherent group.ConclusionIntervention to facilitate conversion from intravenous to oral administration has reduced excess use of intravenous fluoroquinolones and length of hospital stay. With these findings, further implementations of the ASP extending to other antibiotics may be warranted.

Insuffisance cardiaque

Meningitis due to infection with Bacillus anthracis is considered an infrequent manifestation of the disease but one associated with high mortality. The bioterrorism event in the USA in the autumn of 2001 demonstrated our need for a better understanding of anthrax meningitis, as well as management and antimicrobial therapy. However, human clinical trials are not possible and animal experiments to guide such therapy are limited. An approach to the treatment of anthrax meningitis, based on the pathogenicity of B anthracis, the pharmacokinetics and pharmacodynamics of individual antimicrobial agents, studies of anthrax post-exposure prophylaxis in non-human primates, experience with antimicrobial susceptibility patterns of the 2001 outbreak strain, and the clinical experience with inhalational anthrax cases during the 2001 outbreak is presented. These outbreak data, the failure of previous single-drug regimens, the concerns of resistance, and the need for coverage for other causes of bacterial mengingitis suggest initial treatment of suspected anthrax meningitis should anchor on an intravenous fluoroquinolone and should include one or two other agents with activity against B anthracis and good penetration into the central nervous system. Such other agents include penicillin, ampicillin, meropenem, vancomycin, and rifampicin.

Parenteral to Oral Conversion of Fluoroquinolones: Low-Hanging Fruit for Antimicrobial Stewardship Programs?

To estimate avoidable intravenous (IV) fluoroquinolone use in Veterans Affairs (VA) hospitals. A retrospective analysis of bar code medication administration (BCMA) data. Acute care wards of 128 VA hospitals throughout the United States. Data were analyzed for all medications administered on acute care wards between January 1, 2006, and December 31, 2010. Patient-days receiving therapy were expressed as fluoroquinolone-days (FD) and divided into intravenous (IV; all doses administered intravenously) and oral (PO; at least one dose administered per os) FD. We assumed IV fluoroquinolone use to be potentially avoidable on a given IV FD when there was at least 1 other medication administered via the enteral route. Over the entire study period, 884,740 IV and 830,572 PO FD were administered. Overall, avoidable IV fluoroquinolone use accounted for 46.8% of all FD and 90.9% of IV FD. Excluding the first 2 days of all IV fluoroquinolone courses and limiting the analysis to the non-ICU setting yielded more conservative estimates of avoidable IV use: 20.9% of all FD and 45.9% of IV FD. Avoidable IV use was more common for levofloxacin and more frequent in the ICU setting. There was a moderate correlation between avoidable IV FD and total systemic antibiotic use (r = 0.32). Unnecessary IV fluoroquinolone use seems to be common in the VA system, but important variations exist between facilities. Antibiotic stewardship programs could focus on this patient safety issue as a "low-hanging fruit" to increase awareness of appropriate antibiotic use.

Clinical efficacy of intravenous ciprofloxacin in patients with biliary tract infection: a randomized controlled trial with carbapenem as comparator

We conducted a randomized controlled trial (RCT) to evaluate the clinical efficacy of an intravenous fluoroquinolone, ciprofloxacin (CIP), in patients with biliary tract infection requiring biliary drainage using imipenem/cilastatin (IPM/CS) as a control. After the initial collection of bile, patients were randomly assigned to receive CIP at 300 mg twice daily by intravenous drip infusion or IPM/CS at 500 mg twice daily by intravenous drip infusion with the envelope method. The characteristics of the 104 patients evaluated for efficacy were well balanced. The clinical response rates were 100.0% (50/50 patients) in the CIP group and 94.4% (51/54) in the IPM/CS group. The difference in clinical response rate between groups (CIP, IPM/CS) was 5.56% (90% confidence interval: -0.26%, 13.95%), and the non-inferiority of CIP to IPM/CS was confirmed. Adverse events for which causal relationships with the study drugs could not be ruled out developed in 5.4% (3/56) of patients in the CIP group and 5.2% (3/58) of patients in the IPM/CS group, and none of them were serious. The clinical efficacy of CIP in treating biliary tract infection requiring drainage was comparable to that of IPM/CS. These findings suggest that CIP is useful as a new therapeutic option for biliary tract infection.

Méningoencéphalite à Chlamydiae pneumoniae ?

Meningoencephalitis attributed to Chlamydiae pneumoniae has rarely been reported in the literature. We describe the case of a 21-year-old-man admitted for a meningeal syndrome and fever associated with respiratory symptoms and a temporal syndrome. Even though the clinical presentation and certain serological results suggested Chlamydiae infection, some of the biological data raised the possibility of Epstein Barr Virus infection. Intravenous fluoroquinolone therapy led to a successful outcome. Meningoencephalitis associated with non neurological symptoms, especially respiratory symptoms, is suggestive of Chlamydia pneumoniae infection. A broad spectrum antibiotic should be prescribed.

An interventional program to improve antibiotic use.

Large volume and often inappropriate use of specific antimicrobial agents increase selective pressure for emergence of resistant bacteria and place strain on the pharmacy budget. To initiate a multidisciplinary program designed to align intravenous vancomycin and fluoroquinolone prescribing practices with guidelines for appropriate use of these agents. A multidisciplinary, prospective interventional program was implemented to encourage early discontinuation of inappropriate vancomycin and fluoroquinolone therapy and decrease inappropriate duplicative gram-negative coverage using fluoroquinolones. A computerized review was performed for patients receiving intravenous vancomycin and fluoroquinolones for 1998 in a Veterans Affairs Medical Center. In June 1999, guidelines were disseminated and an interventional program was initiated, with a monthly conference for medical residents regarding antimicrobial resistance and local hospital practices. Concurrently, a prospective review of new orders was assessed by the clinical pharmacist and interventions performed when inappropriate use occurred. The interventional program was successful in reducing unnecessary duplicative gram-negative coverage with intravenous fluoroquinolones by 26% (p < 0.001) from 1998 to 2001. Overall, a 43% reduction in the number of courses of intravenous fluoroquinolones was seen during these 4 years. Courses lasting >5 days were reduced by 22% (p < 0.001). Vancomycin prescriptions deemed inappropriate that were administered >5 days were reduced by 16% (p < 0.001) during the same time period. The interventions performed by the clinical pharmacist were deemed successful, with a 76% acceptance rate by providers. Education of physicians through monthly conferences and personal interventions resulted in an increase in appropriate empiric antibiotic use, a decrease in the duration of inappropriate use, and a decrease in duplicate gram-negative coverage.

Diagnosis and treatment of legionella pneumonia

Legionellosis is a relatively rare condition but nevertheless is associated more frequently than many other pathogens with a severe course. Therefore, establishing a diagnosis of Legionellosis remains a challenge. The most significant progress in the diagnosis of Legionellosis is antigen-testing in urine by a rapid immunochromatographic test (ICT). This is an easy to handle bedside test which provides a result within 15 minutes. Sensitivity and specificity reach 80 % and 100 %, respectively. However, the exact place of this test within algorithms of clinical decision making still remains unsettled. Macrolides, doxycycline, fluoroquinolones and ketolides, and possibly also streptogramins are drugs with definitely or most probably sufficient activity against Legionella spp. and, therefore, are appropriate candidates within empirical initial antimicrobial treatment regimen of community-acquired pneumonia. Macrolides and fluoroquinolones should be the drugs of choice for the treatment of established Legionellosis. Oral macrolides should be prefered in patients with mild to moderate pneumonia; within the macrolides, azithromycin has the most favourable profile of activity. Alternatively, ciprofloxacin, levofloxacin and moxifloxacin may be selected. In severe Legionellosis as well as independently of severity in nosocomial legionellosis and immunosuppressed patients, intravenous fluoroquinolones are first choice drugs. Alternatively, azithromycin may be used. Whether a combination treatment including azithromycin or fluoroquinolones with rifampin or azithromycin with fluoroquinolone exert superior activity remains currently unknown.

High-Dose Intravenous Fluoroquinolones in the Treatment of Severe Infections

A bacterial infection should be considered “serious” in case of underlying disease, nosocomial origin, antibiotic resistant pathogen, and/or poor delivery of antibiotics at the site of infection. Treatment of most serious infections requires parenteral administration of antimicrobial agents. Intravenous fluoroquinolones are a class of antimicrobial agents from which physicians must choose when treating nosocomial infections. Fluoroquinolones are bactericidal antimicrobial agents that act by inhibiting DNA gyrase. They are active in vitro against most Gram-negative bacteria and methicillin-susceptible staphylococci. Activity against anaerobic bacteria and streptococci is poor. The rapid development of bacterial resistance in centers with high quinolone usage is of great concern. Resistance develops most commonly in Pseudomonas aeruginosa and staphylococci. Most clinical trials with ciprofloxacin, ofloxacin, pefloxacin, the fluroquinolones currently available in France for parenteral use, are almost 10 years old. There are few studies with higher dosage and most of them have been carried out with ciprofloxacin. The findings of these studies indicate that higher dosage regimens of i.v. ciprofloxacin are much more effective against severe nososcomial infections than is the dosage of 200 mg twice daily. The higher dosage regimens resulted in greater rates of clinical cure and improvement in both monomicrobial and polymicrobial infections. Although the overall frequency of side effects to fluoroquinolones is low, seizures and allergic reactions have been attributed to their use.

Nosocomial Acinetobacter baumannii infections: microbiological and clinical epidemiology.

Acinetobacter baumannii is an important opportunistic pathogen that is rapidly evolving toward multidrug resistance and is involved in various nosocomial infections that are often severe. It is difficult to prevent A. baumannii infection because A. baumannii is ubiquitous and the epidemiology of the infections it causes is complex. To study the epidemiology of A. baumannii infections and assess the relation between fluoroquinolone use and the persistence of multidrug-resistant clones. Three case-control studies and a retrospective cohort study. A 20-bed medical and surgical intensive care unit. Acinetobacter baumannii was isolated from 45 patients in urine (31%), the lower respiratory tract (26.7%), wounds (17.8%), blood (11.1%), skin (6.7%), cerebrospinal fluid (4.4%), and sinus specimens (2.2%). One death was due to A. baumannii infection. Antimicrobial resistance pattern and molecular typing were used to characterize isolates. The incidence of A. baumannii infection and the use of fluoroquinolones were calculated annually. Initially, 28 patients developed A. baumannii infection. Eleven isolates had the same antimicrobial susceptibility profile, genotypic profile, or both (epidemic cases), and 17 were heterogeneous (endemic cases). A surgical procedure done in an emergency operating room was the main risk factor for epidemic cases, whereas previous receipt of a fluoroquinolone was the only risk factor for endemic cases. The opening of a new operating room combined with the restriction of fluoroquinolone use contributed to a transitory reduction in the incidence of infection. When a third epidemiologic study was done, previous receipt of a fluoroquinolone was again an independent risk factor and a parallel was seen between the amount of intravenous fluoroquinolones prescribed and the incidence of endemic infection. Epidemic infections coexisted with endemic infections favored by the selection pressure of intravenous fluoroquinolones.

Assessment of the synergistic interactions of levofloxacin and ampicillin against Enterococcus faecium by the checkerboard agar dilution and time-kill methods

Multidrug-resistant enterococci have become increasingly difficult to eradicate in a growing number of nosocomial infections. With the emergence of vancomycin-resistant enterococci, the use of synergistic antibiotic combinations has become one of the only remaining therapeutic options. Levofloxacin, the active l-isomer of ofloxacin, is a new oral and intravenous fluoroquinolone with a broad spectrum of activity against numerous Gram-positive, Gram-negative, and atypical organisms. The in vitro activity of levofloxacin, alone and in combination with ampicillin, against recent clinical isolates of Enterococcus faecium was assessed for synergistic interactions using the checkerboard agar dilution technique and time-kill methodology. Against all strains, the static technique of checkerboard agar dilution demonstrated indifferent or additive effects for the ampicillin + levofloxacin combination. With the dynamic time-kill technique, synergy was demonstrated for ampicillin (16 μg/ml) + levofloxacin (2 μg/ml) combination against three levofloxacin-sensitive, ampicillin-resistant isolates. At 24 h, the combination yielded a ≥2-log 10 decrease in CFU/ml compared to levofloxacin alone, while ampicillin had negligible effects. Against both a levofloxacin-intermediate, ampicillin-resistant isolate, and a highly levofloxacin-resistant, ampicillin-resistant isolate, none of the ampicillin + levofloxacin combinations tested demonstrated a synergistic interaction. The time-kill method suggested synergy for the ampicillin + levofloxacin combination against some strains of E. faecium.