The electrophysiological masking level difference: effects of age and mediation of hearing and cognition.

OBJECTIVE: Evaluate the conceptual framework that age effects on the electrophysiological binaural masking level difference (MLD) are partially mediated by age-related hearing loss and/or global cognitive function via mediation analysis. DESIGN: Participants underwent a series of audiometric tests. The MLD was measured via cortical auditory evoked potentials using a speech stimulus (/ɑ/) in speech-weighted background noise. We used mediation analyses to determine the total effect, natural direct effects, and natural indirect effects, which are displayed as regression coefficients ([95% CI]; p value). STUDY SAMPLE: Twenty-eight individuals aged 19-87 years (mean [SD]: 53.3 [25.2]), recruited from the community. RESULTS: Older age had a significant total effect on the MLD (-0.69 [95% CI: -0.96, -0.45]; p < 0.01). Neither pure tone average (-0.11 [95% CI: -0.43, 0.24; p = 0.54] nor global cognitive function (-0.02 [95% CI: -0.13, 0.02]; p = 0.55) mediated the relationship of age and the MLD and effect sizes were small. Results were insensitive to use of alternative hearing measures or inclusion of interaction terms. CONCLUSIONS: The electrophysiological MLD may be an age-sensitive measure of binaural temporal processing that is minimally affected by age-related hearing loss and global cognitive function.

Predicting hearing aid use in adults: the Beaver Dam Offspring Study.

OBJECTIVE: The purpose of this study was to (i) develop a model that predicts hearing aid (HA) use and (ii) determine if model fit is improved by adding factors not typically collected in audiological evaluations. DESIGN: Two models were created and evaluated. The "clinical" model used factors typically collected during audiologic clinical evaluations. The "expanded" model considered additional clinical, health and lifestyle factors to determine if the model fit could be improved (compared to clinical model). Models were created with least absolute shrinkage and selection operator (LASSO) logistic regression with 10-fold cross validation. Predictive ability was evaluated via receiver operating characteristic curves and concordance statistics (c-statistics). STUDY SAMPLE: This study included 275 participants from the Beaver Dam Offspring Study, a prospective longitudinal cohort study of aging, with a treatable level of hearing loss and no HA use at baseline. RESULTS: The clinical and expanded models report predictors important for HA use. The c-statistics of the clinical (0.80) and expanded (0.79) models were not significantly different (p = 0.41). CONCLUSIONS: Similar predictive abilities of models suggest audiological evaluations perform well in predicting HA use.

Vestibular Function and Motion Sickness Susceptibility: Videonystagmographic Evidence From Oculomotor and Caloric Tests.

Purpose Motion sickness (MS) is a common condition that affects millions of individuals. Although the condition is common and can be debilitating, little research has focused on the vestibular function associated with susceptibility to MS. One causal theory of MS is an asymmetry of vestibular function within or between ears. The purposes of this study, therefore, were (a) to determine if the vestibular system (oculomotor and caloric tests) in videonystagmography (VNG) is associated with susceptibility to MS and (b) to determine if these tests support the theory of an asymmetry between ears associated with MS susceptibility. Method VNG was used to measure oculomotor and caloric responses. Fifty young adults were recruited; 50 completed the oculomotor tests, and 31 completed the four caloric irrigations. MS susceptibility was evaluated with the Motion Sickness Susceptibility Questionnaire-Short Form; in this study, percent susceptibility ranged from 0% to 100% in the participants. Participants were divided into three susceptibility groups (Low, Mid, and High). Repeated-measures analyses of variance and pairwise comparisons determined significance among the groups on the VNG test results. Results Oculomotor test results revealed no significant differences among the MS susceptibility groups. Caloric stimuli elicited responses that were correlated positively with susceptibility to MS. Slow-phase velocity was slowest in the Low MS group compared to the Mid and High groups. There was no significant asymmetry between ears in any of the groups. Conclusions MS susceptibility was significantly and positively correlated with caloric slow-phase velocity. Although asymmetries between ears are purported to be associated with MS, asymmetries were not evident. Susceptibility to MS may contribute to interindividual variability of caloric responses within the normal range.

Electrophysiological Evidence for the Sources of the Masking Level Difference.

Purpose: The purpose of this review article is to review evidence from auditory evoked potential studies to describe the contributions of the auditory brainstem and cortex to the generation of the masking level difference (MLD). Method: A literature review was performed, focusing on the auditory brainstem, middle, and late latency responses used in protocols similar to those used to generate the behavioral MLD. Results: Temporal coding of the signals necessary for generating the MLD occurs in the auditory periphery and brainstem. Brainstem disorders up to wave III of the auditory brainstem response (ABR) can disrupt the MLD. The full MLD requires input to the generators of the auditory late latency potentials to produce all characteristics of the MLD; these characteristics include threshold differences for various binaural signal and noise conditions. Studies using central auditory lesions are beginning to identify the cortical effects on the MLD. Conclusions: The MLD requires auditory processing from the periphery to cortical areas. A healthy auditory periphery and brainstem codes temporal synchrony, which is essential for the ABR. Threshold differences require engaging cortical function beyond the primary auditory cortex. More studies using cortical lesions and evoked potentials or imaging should clarify the specific cortical areas involved in the MLD.

Hyperinsulinemia/diabetes, hearing, and aging in the University of Wisconsin calorie restriction monkeys.

The purpose of this study was to determine the effects of hyperinsulinemia/Type 2 diabetes mellitus (HI-T2DM) on hearing impairment using rhesus monkeys to obtain control over diet and lifestyle factors that confound human studies. The study is a retrospective evaluation of rhesus monkeys from the Wisconsin National Primate Research Center (WNPRC) study on caloric restriction and aging. The research questions were the following: 1. Is HI-T2DM related to hearing impairment? 2. If so, what is the site of lesion in the auditory system? and 3. What physiological factors affect the risk of hearing loss in HI-T2DM? Three groups of eight monkeys each were matched by sex and age; the caloric restricted (CR) monkeys had a reduced risk of diabetes, the normal control (NL) group had a normal risk, and the hyperinsulinemia/diabetes (HI-D) group had already developed HI-T2DM. Auditory testing included distortion product otoacoustic emissions (DPOAEs) with f2 frequencies from 2211 to 8837 Hz and auditory brainstem responses (ABRs) obtained with clicks and tone bursts (8, 16, and 32 kHz). DPOAEs had signal-to-noise ratios 8-17 dB larger in the NL group than in the HI-D and CR groups, signifying that cochlear function was best in the NL group. ABR thresholds were 5-8 dB better in the NL group than in the HI-D group, although no significant differences across the groups were evident for the thresholds, latencies, interwave intervals, or amplitudes. Correlations were significant for quadratic relations between body mass index (BMI) and DPOAE, with largest DPOAEs for animals in the middle of the BMI range. ABR thresholds elicited with 16 and 32 kHz signals were significantly correlated, positively with BMI and HbA1c, and negatively with KG (glucose tolerance), SI (insulin sensitivity index) and DI (disposition index). These findings suggest that the hearing loss associated with HI-T2DM is predominantly cochlear, and auditory structures underlying the higher frequencies are at risk with HI-T2DM. Loss of auditory function begins in the hyperinsulinemia, pre-diabetic state.

Effects of motion sickness severity on the vestibular-evoked myogenic potentials.

BACKGROUND: Motion sickness is a common debilitating condition associated with both actual and perceived motion. Despite the commonality, little is known about the underlying physiological mechanisms. One theory proposes that motion sickness arises from a mismatch between reality and past experience in vertical motions. Physiological tests of the vestibular system, however, have been inconclusive regarding the underlying pathogenesis. Cervical vestibular-evoked myogenic potentials (cVEMPs) arise from the saccule, which responds to vertical motion. If vertical motion elicits motion sickness, the cVEMP should be affected. PURPOSE: The purpose of this investigation was to determine if cVEMP characteristics differ among individuals with a range of motion sickness susceptibility from negligible to severe. The hypothesis was that individuals with high susceptibility would have larger cVEMP amplitudes and shorter cVEMP latencies relative to those who are resistant to motion sickness. RESEARCH DESIGN: The study had two parts. The first was quasi-experimental in which participants comprised three groups based on susceptibility to motion sickness (low, mild-moderate, high) as identified on the short version of the Motion Sickness Susceptibility Questionnaire (MSSQ-S). The second part of the study was correlational and evaluated the specific relationships between the degree of motion sickness susceptibility and characteristics of the VEMPs. STUDY SAMPLE: A total of 24 healthy young adults (ages 20-24 yr) were recruited from the university and the community without regard to motion sickness severity. DATA COLLECTION AND ANALYSIS: Participants took the MSSQ-S, which quantifies susceptibility to motion sickness. The participants had a range of motion sickness susceptibility with MSSQ raw scores from 0.0-36.6, which correspond to percent susceptibility from 0.0-99.3%. VEMPs were elicited by 500 Hz tone-bursts monaurally in both ears at 120 dB pSPL. MSSQ-S percent scores were used to divide the participants into low, mild-moderate, and high susceptibility groups. A fixed general linear model with repeated-measures analysis of variance tested cVEMP characteristics for the susceptibility groups (between participants) and ears (within participants). A univariate analysis of variance tested the cVEMP interaural amplitudes across groups. The second analysis was a regression of the severity of motion sickness in percent on cVEMP characteristics. Significance was defined as p < 0.05. RESULTS: Participants in the high susceptibility group had significantly higher cVEMP amplitudes than those in the low susceptibility group. cVEMP amplitudes did not differ between ears, and latencies did not differ between the two groups or between ears. Regression analysis on MSSQ-S percent susceptibility by VEMP amplitudes revealed a best-fit cubic function in both ears, with r(2) values of more than 42%. The interaural asymmetry ratio was negatively associated with motion sickness susceptibility (r(2) = 0.389). CONCLUSIONS: The current study is the first to report that greater susceptibility to motion sickness is associated with larger cVEMP amplitudes and lower interaural cVEMP asymmetries. Larger interaural asymmetries in cVEMPs did not promote motion sickness susceptibility. The cVEMP findings implicate the saccule and its neural pathways in the production of motion sickness and are consistent with the theory that vertical motions elicit motion sickness. Motion sickness susceptibility may contribute to the variability in normative cVEMP amplitudes.

Frequency dependence of binaural interaction in the auditory brainstem and middle latency responses.

PURPOSE: The primary purpose of this investigation was to determine the relative frequency representation of binaural function in the brainstem and cortex of adults. The secondary purpose was to compare adult responses to previously reported infant responses. METHODS: Simultaneous auditory brainstem responses and auditory middle responses were recorded monaurally and binaurally in 20 young women. The binaural (BIN) response was subtracted from the summed monaural waves (L+R) to obtain the binaural interaction components (BIC) from waves V (peak A) and Pa (BIC-Pa). Amplitude ratios were calculated as BIC/L+R. Repeated-measures analyses of variance evaluated responses to frequency (500 Hz vs. 4000 Hz), wave condition (L+R vs. BIN), and wave class (auditory brainstem response vs. auditory middle response). RESULTS: Waveforms were present for all conditions. The L+R responses were larger than the BIN responses, 500 Hz produced larger amplitudes than 4000 Hz, and Pa was larger than wave V. The largest response, overall, was the Pa(L+R) response to 500 Hz. For amplitude ratios, BIC-Pa/Pa(L+R) was larger than Peak A/[V(L+R)]. CONCLUSION: More neural resources are devoted to binaural function in the cortex than in the brainstem, and more resources are devoted to lower frequencies than to higher frequencies. The adult data confirm that previously recorded infant data reveal binaural immaturity. Longitudinal data should characterize developmental characteristics of binaural function.

Relationships among standard and wideband measures of middle ear function and distortion product otoacoustic emissions.

BACKGROUND: The overall goal of the current study was to examine the relationships among uncompensated admittance (Ya) at ambient pressure extracted from tympanograms, energy reflectance (ER) measures at ambient pressure from wideband acoustic transfer functions (WATF), and distortion product otoacoustic emissions (DPOAEs). If WATF measures of Ya are comparable to tympanometric measures of Ya at ambient pressure, it would be further evidence that the two systems provide comparable information at ambient pressure. Such a relationship could be used as a cross-check or validation for WATF measures and support the use of WATFs in lieu of tympanograms in some applications. Finally, if WATF measures of Ya and/or ER at DPOAE stimulus frequencies can account for some of the variability observed in DPOAE levels and/or signal-to-noise ratios (SNRs) in ears with normal hearing, the relationships could be used to improve hearing screening procedures. PURPOSE: The hypotheses were as follows: (1) measures of Ya at ambient pressure are significantly correlated as measured with tympanometric and WATF procedures and (2) measures of Ya and ER at DPOAE stimulus frequencies are significantly correlated with DPOAE level and SNR. RESEARCH DESIGN: Repeated measures in human adults. STUDY SAMPLE: Forty ears of 20 adults with normal hearing and middle ear function were included in the final sample. DATA COLLECTION AND ANALYSIS: Tympanograms were obtained using probe frequencies of 226, 678, and 1000 Hz; WATFs were obtained using a click probe, and DPOAEs were elicited with f2's of 1000, 2000, and 4000 Hz. A repeated measures analysis of variance (RM-ANOVA) was completed to identify significant differences between ears and among probe frequencies for Ya measured at ambient pressure from the Tympstar and for Ya measured at the three closest frequencies on the WATFs. Lines were fit to the comparison of Ya from the Tympstar and WATF, and percent variance accounted for (r2) was calculated. Ya and ER were extracted at all stimulus frequencies that were used to elicit DPOAEs and were compared to DPOAE levels and SNRs. RM-ANOVAs were completed to identify any significant differences in DPOAE level and SNR between ears and among f2 conditions. Lines were fit to the comparison of Ya and ER measures at f1 and f2 with the DPOAE levels and SNRs. The relationship between behavioral air conduction threshold at each f2 and DPOAE level (and SNR) was examined with regression analysis. RESULTS: Ya was significantly correlated between the tympanometric and WATF measures at all three probe-tone frequencies. Ya and ER at f1 and f2 were significantly correlated with DPOAE level for f2 = 4000 Hz. CONCLUSIONS: The implications are as follows: (1) WATFs, which can be obtained with the same probe microphone system as DPOAEs, could be used as a supplement to tympanometry in a diagnostic test battery, and the relationship between Ya measured on the two systems could be used for verification, and (2) Ya and ER measures from WATFs at both DPOAE stimulus frequencies account for some of the variability observed in DPOAE levels at f2 = 4000 Hz in normal ears.

Clinical breakpoints for voriconazole and Candida spp. revisited: review of microbiologic, molecular, pharmacodynamic, and clinical data as they pertain to the development of species-specific interpretive criteria.

We reassessed the Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) for voriconazole. We examined i) the essential (EA: ±2 dilutions) and categorical agreement between 24-h CLSI and EUCAST methods for voriconazole testing of Candida, ii) wild-type (WT) MICs and epidemiologic cutoff values (ECVs) for voriconazole by both CLSI and EUCAST methods, and iii) correlation of MICs with outcomes from previously published data using CLSI methods. We applied these findings to propose new 24-h species-specific CLSI CBPs. Adjusted 24-h CBPs for voriconazole and C. albicans, C. tropicalis, and C. parapsilosis (susceptible, ≤ 0.125 µg/mL; intermediate, 0.25-0.5 µg/mL; resistant, ≥ 1 µg/mL) should be more sensitive for detecting emerging resistance among common Candida species and provide consistency with EUCAST CBPs. In the absence of CBPs for voriconazole and C. glabrata (and less common species), we recommend that their respective ECVs be used to detect the emergence of non-WT strains.

Procalcitonin for triage of patients with respiratory tract symptoms: a case study in the trial design process for approval of a new diagnostic test for lower respiratory tract infections.

Symptoms of cough, fever, chest pain, and shortness of breath are common reasons that patients seek medical care, and they can be due to a variety of medical conditions, including lower respiratory tract infection (LRTI). Only a small proportion of these patients will actually have a bacterial etiology, but many will receive antibiotic treatment because physicians cannot readily determine the etiology at the time of presentation. Current diagnostic methodologies are not sensitive or specific enough to reliably distinguish bacterial from viral or noninfectious etiologies. Procalcitonin (PCT) is a marker of host response. PCT serum levels are elevated in patients with bacterial infection, compared with levels in those with viral infections or other inflammatory pulmonary conditions. Studies have suggested that the determination of PCT levels can identify a subset of patients with LRTI symptoms who can safely avoid antibiotic treatment. As with any new test, clinical trials are necessary to demonstrate the safety and efficacy of the test to obtain U.S. Food and Drug Administration clearance. However, in the absence of standard reference methods for comparison that are reliably sensitive and specific, meeting the regulatory requirements for proof of safety and efficacy is a major challenge. Additional challenges include the choice of study design, the definition and determination of end points, and the justification of statistical analysis.

Auditory function in rhesus monkeys: effects of aging and caloric restriction in the Wisconsin monkeys five years later.

Caloric restriction (CR) slows aging in many species and protects some animals from age-related hearing loss (ARHL), but the effect on humans is not yet known. Because rhesus monkeys are long-lived primates that are phylogenically closer to humans than other research animals are, they provide a better model for studying the effects of CR in aging and ARHL. Subjects were from the pool of 55 rhesus monkeys aged 15-28 years who had been in the Wisconsin study on CR and aging for 8-13.5 years. Distortion product otoacoustic emissions (DPOAE) with f2 frequencies from 2211 to 8837 Hz and auditory brainstem response (ABR) thresholds from clicks and 8, 16, and 32 kHz tone bursts were obtained. DPOAE levels declined linearly at approximately 1 dB/year, but that rate doubled for the highest frequencies in the oldest monkeys. There were no interactions for diet condition or sex. ABR thresholds to clicks and tone bursts showed increases with aging. Borderline significance was shown for diet in the thresholds at 8 kHz stimuli, with monkeys on caloric restriction having lower thresholds. Because the rhesus monkeys have a maximum longevity of 40 years, the full benefits of CR may not yet be realized.

Tympanometry in rhesus monkeys: effects of aging and caloric restriction.

Caloric restriction is the only known method of increasing lifespan in laboratory animals. The present study was conducted as part of a larger investigation into the effect of caloric restriction on longevity of rhesus monkeys as a model for human aging. This study focused on the effects of caloric restriction and aging on measures of middle-ear function measured with tympanometry. Peak compensated static acoustic admittance (peak Y(tm)) tended to be reduced with aging. For tympanometric width (TW), the effect of age was significant with TW increasing with age. Males had a trend of narrower TW than females. A significant age by sex interaction indicated that TW for males stays relatively constant, whereas TW for females increases with age. The equivalent ear canal volume (V(ea)) was significantly larger in male monkeys than in female monkeys, and marginally larger for the control monkeys than for the caloric restricted monkeys. These results parallel many findings in middle-ear function in aging humans. Longitudinal studies are planned.

The reciprocal effects of eating disorders and the postpartum period: a review of the literature and recommendations for clinical care.

This paper examines the areas of psychological and physiological concern when working with patients who have eating disorders as they move through the postpartum period. These concerns include infant feeding, maternal-child bonding, and postpartum adjustment. The combination of psychological stressors of new motherhood and body image concerns intensified by the residual bodily changes of pregnancy may predispose women to have an exacerbation in eating disordered symptoms as well as the development of postpartum mood disorders. Depression can lead mothers to be nonresponsive, inconsistent, or rejecting of the infant, placing the mother-baby attachment at risk. The added existence of an eating disorder compounds these risks, with medical and psychological risks becoming increasingly apparent. Healthcare providers (e.g., primary care physician, obstetric provider) are more likely to have contact with women during the postpartum period, making such providers instrumental in the screening and referral process. A multidisciplinary approach is recommended for treating eating disorders and related conditions. Unfortunately, there is little information about the efficacy and appropriateness of standard eating disorder treatments for women in the postpartum period. In addition to reviewing the literature, guidance is offered on how to assess and treat patients with eating disorders in general as well as considerations specific to the postpartum period.

Sudden bilateral sensorineural hearing loss following speedballing.

BACKGROUND: Hearing loss is an infrequently-reported consequence of recreational drug abuse. Although there are sporadic reports of hearing loss from heroin and cocaine ingested separately, there are no reports of hearing loss resulting from the combination of both drugs ingested simultaneously in the form of speedballing. PURPOSE: The purpose of this report is to document a case of bilateral sensorineural hearing loss associated with an episode of speedballing. RESEARCH DESIGN: Case Report. DATA COLLECTION AND ANALYSIS: The subject of this report was a 40-year-old man with a 20-year history of substance abuse. Data collected included a case history, pure tone audiometry, tympanometry and acoustic reflexes, and transient evoked otoacoustic emissions. RESULTS: The audiologic evaluation indicated a mild to moderate, relatively flat, bilateral sensorineural hearing loss that was worse in the right ear. CONCLUSIONS: A bilateral sensorineural hearing loss involving both cochlear and neural pathology may be a rare complication of cocaine, heroin, or the combination of the two drugs.

Amplitude-modulated auditory steady-state responses in younger and older listeners.

The primary purpose of this investigation was to determine whether temporal coding in the auditory system was the same for younger and older listeners. Temporal coding was assessed by amplitude-modulated auditory steady-state responses (AM ASSRs) as a physiologic measure of phase-locking capability. The secondary purpose of this study was to determine whether AM ASSRs were related to behavioral speech understanding ability. AM ASSRs showed that the ability of the auditory system to phase lock to a temporally altered signal is dependent on modulation rate, carrier frequency, and age of the listener. Specifically, the interaction of frequency and age showed that younger listeners had more phase locking than old listeners at 500 Hz. The number of phase-locked responses for the 500 Hz carrier frequency was significantly correlated to word-recognition performance. In conclusion, the effect of aging on temporal processing, as measured by phase locking with AM ASSRs, was found for low-frequency stimuli where phase locking in the auditory system should be optimal. The exploration, and use, of electrophysiologic responses to measure auditory timing analysis in humans has the potential to facilitate the understanding of speech perception difficulties in older listeners.

Assessment of auditory function in rhesus monkeys (Macaca mulatta): effects of age and calorie restriction.

Age-related alterations in auditory function were evaluated in adult male rhesus monkeys (Macaca mulatta) involved in a long-term study evaluating the effects of caloric restriction (CR) on aging. We assessed 26 monkeys in a control group fed a low fat, high fiber diet at approximately ad libitum levels and 24 monkeys in a CR group that were fed the same diet reduced in amount by 30% compared to age- and weight-matched controls. The following measures of auditory function were obtained while monkeys were maintained under anesthesia: (1) distortion product otoacoustic emissions (DPOAEs); (2) auditory brainstem responses (ABRs); and (3) middle latency responses (MLRs). All DPOAE measures and peak II amplitude significantly decreased with age, while peak IV latency and ABR threshold significantly increased with age. We found no significant effects of CR on any auditory parameters examined.

Relationship between fluoroquinolone area under the curve: minimum inhibitory concentration ratio and the probability of eradication of the infecting pathogen, in patients with nosocomial pneumonia.

Our objective was to prospectively determine the factors influencing the probability of a good microbiological or clinical outcome in patients with nosocomial pneumonia treated with a fluoroquinolone. Levofloxacin was administered as an infusion of 500 mg/h for 1.5 h (total dose, 750 mg). For patients with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus, a second drug was added (ceftazidime or piperacillin/tazobactam for P. aeruginosa and vancomycin for methicillin-resistant S. aureus). Population pharmacokinetic studies of 58 patients demonstrated that this population handled the drug differently from populations of volunteers. Multivariate logistic regression analysis (n=47 patients) demonstrated that only the age of the patient and the achievement of an area under the curve: minimum inhibitory concentration ratio of > or =87 had a significant effect on eradication of the pathogen (P<.001). Achieving the breakpoint made the patient 4 times more likely to achieve eradication. The effect was greatest in patients > or =67 years old.

Levofloxacin compared with imipenem/cilastatin followed by ciprofloxacin in adult patients with nosocomial pneumonia: a multicenter, prospective, randomized, open-label study.

BACKGROUND: Therapy of nosocomial pneumonia is usually empiric and includes > or = 1 broad-spectrum antimicrobial agent. When considering the use of fluoroquinolones in these difficult-to-treat infections--in which drug delivery to the site of infection may be impaired or organisms with higher minimum inhibitory concentrations may be present--an agent should be chosen whose pharmacodynamics ensure maximal drug exposure. Use of the 750-mg dose of levofloxacin should enhance therapeutic benefit in patients with nosocomial pneumonia. OBJECTIVE: The goal of this study was to compare the efficacy and safety of levofloxacin 750 mg and imipenem/cilastatin followed by ciprofloxacin in adult patients with nosocomial pneumonia. METHODS: This was a multicenter, prospective, randomized, open-label trial conducted in North America. Patients were randomly assigned to 1 of 2 treatment arms: levofloxacin 750 mg QD given i.v. and then orally for 7 to 15 days or imipenem/cilastatin 500 mg to 1 g i.v. every 6 to 8 hours, followed by oral ciprofloxacin 750 mg every 12 hours for 7 to 15 days. Adjunctive antibacterial therapy was mandatory in patients with documented or suspected Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus infection. The primary predefined outcome measure was the clinical response (cure, improvement, failure, or unable to evaluate) in microbiologically evaluable patients 3 to 15 days after the end of therapy. RESULTS: The study enrolled 438 adult patients (315 men, 123 women; mean [SD] age, 55.7 [20.04] years). Two hundred twenty patients received levofloxacin, and 218 received the comparator regimen. Demographic and baseline clinical characteristics were similar in the intent-to-treat and clinically evaluable populations. In patients evaluable for microbiologic efficacy, clinical success (cure or improvement) was achieved in 58.1% (54/93) of patients who received levofloxacin, compared with 60.6% (57/94) of patients who received the comparator regimen (95% CI, -12.0 to 17.2). Similar clinical results were seen in patients evaluable for clinical efficacy and in the intent-to-treat population. In the 187 patients evaluable for microbiologic efficacy, eradication was achieved in 66.7% (62/93) of patients receiving levofloxacin and 60.6% (57/94) of patients receiving the comparator regimen (95% CI, -20.3 to 8.3). CONCLUSION: In this study, levofloxacin was at least as effective and was as well tolerated as imipenem/cilastatin followed by ciprofloxacin in adult patients with nosocomial pneumonia, as demonstrated by comparable clinical and microbiologic success rates.

Once-daily, high-dose levofloxacin versus ticarcillin-clavulanate alone or followed by amoxicillin-clavulanate for complicated skin and skin-structure infections: a randomized, open-label trial.

This study tested whether levofloxacin, at a new high dose of 750 mg, was effective for the treatment of complicated skin and skin-structure infections (SSSIs). Patients with complicated SSSIs (n=399) were randomly assigned in a ratio of 1:1 to 2 treatment arms: levofloxacin (750 mg given once per day intravenously [iv], orally, or iv/orally) or ticarcillin-clavulanate (TC; 3.1 g given iv every 4-6 hours) followed, at the investigator's discretion, by amoxicillin-clavulanate (AC; 875 mg given orally every 12 hours). In the clinically evaluable population, therapeutic equivalence was demonstrated between the levofloxacin and TC/AC regimens (success rates of 84.1% and 80.3%, respectively). In the microbiologically evaluable population, the overall rate of eradication was 83.7% in the levofloxacin treatment group and 71.4% in the TC/AC treatment group (95% confidence interval, -24.3 to -0.2). Both levofloxacin and TC/AC were well tolerated. These data demonstrate that levofloxacin (750 mg once per day) is safe and at least as effective as TC/AC for complicated SSSIs.