A phase 3, randomized, double-blind comparison of analgesic efficacy and tolerability of Q8003 vs oxycodone or morphine for moderate-to-severe postoperative pain following bunionectomy surgery.

OBJECTIVE: Compare the efficacy and tolerability of the dual-opioid, Q8003(®) (morphine/oxycodone combination) 12 mg/8 mg to morphine 12 mg or oxycodone 8 mg in subjects following bunionectomy surgery. DESIGN: This was a randomized, double-blind study. SETTING: Hospitalized patients. PATIENTS: Healthy men or women aged ≥18 years with moderate or severe pain (score ≥2 on a 4-point Likert scale) and ≥4 on the 11-point numerical pain rating scale following surgery. INTERVENTIONS: Study medication was initiated after surgery and was given for 48 hours. OUTCOMES: The primary efficacy variable was mean sum of the pain intensity difference (SPID) scores from the postsurgical baseline. RESULTS: Five hundred twenty-two subjects were randomized; 31 (5.9%) discontinued, including 19 (3.6%) for adverse events. The mean total morphine equivalent dose (MED) was 182.7 mg from Q8003 12 mg/8 mg, 92.4 mg for morphine 12 mg, and 92.1 mg for oxycodone 8 mg. SPID from baseline over 24 hours and SPID from baseline over 48 hours were significantly (P < 0.02) higher for Q8003 12 mg/8 mg vs morphine 12 mg or oxycodone 8 mg. Significantly (P < 0.015) fewer subjects in the Q8003 group required ibuprofen rescue medication, used lower doses of rescue medication, and had a longer median time to first use of rescue medication. Oxygen desaturation <90% occurred in 5.3% with Q8003, 2.8% with morphine 12 mg, and 2.3% with oxycodone 8 mg, and the cumulative median dose at first desaturation was twofold greater with Q8003. CONCLUSION: Q8003 provided superior efficacy to its individual components at twice the MED with only a modest increase in the incidence of adverse events.

Community and health worker perceptions and preferences regarding integration of other health services with routine vaccinations: four case studies.

BACKGROUND: Integration of routine vaccination and other maternal and child health services is becoming more common and the services being integrated more diverse. Yet knowledge gaps remain regarding community members and health workers acceptance, priorities, and concerns related to integration. METHODS: Qualitative health worker interviews and community focus groups were conducted in 4 African countries (Kenya, Mali, Ethiopia, and Cameroon). RESULTS: Integration was generally well accepted by both community members and health workers. Most integrated services were perceived positively by the communities, although perceptions around socially sensitive services (eg, family planning and human immunodeficiency virus) differed by country. Integration benefits reported by both community members and health workers across countries included opportunity to receive multiple services at one visit, time and transportation cost savings, increased service utilization, maximized health worker efficiency, and reduced reporting requirements. Concerns related to integration included being labor intensive, inadequate staff to implement, inadequately trained staff, in addition to a number of more broad health system issues (eg, stockouts, wait times). CONCLUSIONS: Communities generally supported integration, and integrated services may have the potential to increase service utilization and possibly even reduce the stigma of certain services. Some concerns expressed related to health system issues rather than integration, per se, and should be addressed as part of a wider approach to improve health services. Improved planning and patient flow and increasing the number and training of health staff may help to mitigate logistical challenges of integrating services.

A novel needle-free powder lidocaine delivery system for rapid local analgesia.

OBJECTIVE: To determine the analgesic effect and tolerability of a novel needle-free powder lidocaine delivery system in children undergoing venipuncture. STUDY DESIGN: In this double-blind, placebo-controlled, single-center trial, 306 children age 3 to 18 years were randomized to receive a needle-free powder lidocaine delivery system or matching sham placebo at the back of the hand 2 to 3 minutes before venipuncture. Venipuncture pain was self-reported using the Wong-Baker FACES scale (in 3- to 12-year-olds) and a 100-mm visual analog scale (in 8- to 18-year-olds). Safety was assessed by adverse events, investigator skin site assessments, and children's self-report of the administration comfort of study treatments. Effect sizes were compared by 2-sample t test and Glass's Delta approach. RESULTS: Subjects receiving the needle-free powder lidocaine delivery system exhibited mean pain reductions (effect size) of 33% to 46% relative to sham placebo. Pain reductions were statistically significant for all ages combined and also for the youngest and oldest age strata. Self-reported administration comfort levels were similar in the active system and sham placebo groups. Incidences of adverse events and dermal reactions were low; the most common dermal reaction was mild erythema. CONCLUSIONS: The needle-free powder lidocaine delivery system was well tolerated and provided effective local analgesia when administered 2 to 3 minutes before venipuncture.

Long-term use of controlled-release oxycodone for noncancer pain: results of a 3-year registry study.

OBJECTIVE: To evaluate the outcomes associated with the use of controlled-release (CR) oxycodone for up to 3 years in the treatment of noncancer pain. METHODS: Adult patients who previously participated in controlled trials of CR oxycodone for osteoarthritis pain, diabetic neuropathy pain, or low back pain, and who continued to require opioid analgesia for moderate or severe pain, were enrolled in an open-label, uncontrolled, registry study. Data collected over time included dose, pain severity on a numeric scale, treatment acceptability, adverse events, and descriptions of problematic drug-related behavior. RESULTS: Two hundred thirty-three patients were enrolled. When the study closed, 141, 86, and 39 patients had taken CR oxycodone for at least 1, 2, and 3 years, respectively; mean duration of treatment was 541.5 days. Among the 219 intent-to-treat patients (received at least 1 dose and provided at least 1 postdose study observation), the mean (SD, range) daily dose was 52.5 (+/-38.5, 10.0 to 293.5) mg. Before the end of month 3, 44% required an increase in total daily dose; this dropped to 23% during months 4 to 6, to 17% during months 10 to 12, and remained at approximately 10% for each time interval thereafter (range 8% to 13%). Among the large majority of patients with stable or lower dose requirements after the initial 3 months of treatment, the average pain intensity ratings were unchanged or improved for approximately 70% to 80% of patients at all subsequent time points through month 33, and for 54% (7/13 patients) at month 36. A decrease in pain was initially seen by the end of month 3, and for the majority of patients, the Average Pain Intensity score remained the same, better, or minimally worse (<3 points) for the remainder of the 3-year study period. The most common adverse events were constipation and nausea, and the incidence of these events declined over time on treatment. Investigators reported 6 cases (2.6%) of possible drug misuse but no evidence of de novo addiction was observed. DISCUSSION: These registry data demonstrate that a subgroup of patients with noncancer pain experienced prolonged relief with tolerable side effects and modest need for dose escalation during long-term therapy with CR oxycodone.

The validity of the neuropathic pain scale for assessing diabetic neuropathic pain in a clinical trial.

OBJECTIVES: In controlled trials of analgesics for the treatment of neuropathic pain, the primary outcome variable is most often a measure of global pain intensity. However, because neuropathic pain is associated with a variety of pain sensations, the effects of analgesic treatments on different sensations could go undetected if specific pain qualities are not assessed. This study sought to evaluate the utility of assessing the multiple components of neuropathic pain in an analgesic clinical trial. METHODS: One hundred fifty-nine subjects with diabetes-related foot pain were randomly assigned to receive an active analgesic (controlled-release oxycodone) or matching placebo for 6 weeks. A multidimensional measure of neuropathic pain, the Neuropathic Pain Scale (NPS), was administered before, during, and after study treatment. RESULTS: Relative to placebo, the opioid analgesic produced statistically significantly greater decreases in global pain intensity, pain unpleasantness, and sharp, dull, and deep pain sensations. Responder analyses indicated a higher rate of responding to the opioid condition, relative to placebo, for intense, unpleasant, deep, and surface pain. The opioid analgesic did not significantly reduce hot, cold, itchy, or sensitive pain sensations compared with placebo in either analysis. CONCLUSIONS: These findings support the utility of the NPS for characterizing the multidimensional nature of the neuropathic pain experience and for detecting changes in neuropathic pain with treatment.

Treatment of persistent pain associated with osteoarthritis with controlled-release oxycodone tablets in a randomized controlled clinical trial.

OBJECTIVE: This study, lasting up to 90 days, was undertaken in patients with osteoarthritis with persistent moderate to severe pain uncontrolled by standard therapy (nonsteroidal anti-inflammatory drugs, acetaminophen, and/or short-acting opioids) to evaluate functional outcomes, as well as efficacy and safety, of controlled-release oxycodone versus placebo. METHODS: One hundred seven patients received either controlled-release oxycodone or placebo every 12 hours in this double blind, randomized, placebo-controlled, parallel-group study. Stable previous regimens of acetaminophen or nonsteroidal anti-inflammatory agents were allowed to continue. Primary efficacy variables included Brief Pain Inventory average pain intensity scores at completion of initial titration, Western Ontario and McMaster Universities Osteoarthritis Index scores at days 30 and 60, and the percentage of patients discontinuing due to inadequate pain control. RESULTS: Controlled-release oxycodone was significantly superior to placebo in decreasing average pain intensity and in reducing pain-induced interference with general activity, walking ability (except at day 30), and normal work, as well as mood, sleep, relations with people (at days 60 and 90), and enjoyment in life. Daily functioning, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index, was also significantly improved in the controlled-release oxycodone group. In the placebo group, a significantly greater percentage of patients discontinued due to inadequate pain control. Adverse events were consistent with opioid adverse events, and no safety concerns were noted. DISCUSSION: Treatment with controlled-release oxycodone of patients with osteoarthritis with persistent moderate to severe pain uncontrolled by standard therapy resulted in significant pain control and improvements in physical functioning.

Comparison of the efficacy and safety of dual-opioid treatment with morphine plus oxycodone versus oxycodone/acetaminophen for moderate to severe acute pain after total knee arthroplasty.

BACKGROUND: In acute pain models, coadministration of low doses of morphine and oxycodone markedly enhanced analgesia relative to either opioid given alone. Enhanced analgesia with coadministration of morphine and oxycodone has also been reported in acute and chronic moderate to severe pain conditions during double-blind studies. OBJECTIVE: The goal of this study was to compare the efficacy and tolerability of a flexible dose regimen of the morphine/oxycodone combination versus oxycodone/acetaminophen and fixed low-dose morphine/oxycodone. METHODS: This was a 5-center, randomized, open-label study of hospitalized patients (n = 44) with acute moderate to severe postoperative pain after total knee arthroplasty. Inpatients were randomized to a flexible dose regimen of morphine/oxycodone (3 mg/2 mg to 24 mg/16 mg), fixed low-dose morphine/oxycodone regimen (3 mg/2 mg), or oxycodone/acetaminophen (5 mg/325 mg). Treatment was initiated following surgery after intravenous (IV) morphine patient-controlled analgesia. An algorithm was evaluated for converting the patient-controlled analgesia morphine dose to an initial oral dose of morphine/oxycodone. The primary efficacy variable was the time-weighted sum of pain intensity difference from 0 to 48 hours. RESULTS: The median values for the sum of the pain intensity difference from 0 to 48 hours for the morphine/oxycodone flexible dose and oxycodone/acetaminophen were similar and approximately twice that of fixed morphine/oxycodone 3 mg/2 mg (148.0, 139.5, and 71.3, respectively). Moderate to severe gastrointestinal adverse events occurred in 50% of patients in the oxycodone/acetaminophen group compared with 15% of the equianalgesic morphine/oxycodone group. On several items of the Brief Pain Inventory (general activity, walking ability, and sleep), the morphine/oxycodone flexible dose produced greater benefit than oxycodone/acetaminophen. CONCLUSIONS: Flexible dose morphine/oxycodone was superior to low-dose morphine/oxycodone and comparable to oxycodone/acetaminophen. Flexible dose morphine/oxycodone-treated patients had a lower rate of moderate to severe nausea or vomiting than equianalgesic oxycodone/acetaminophen-treated patients. Thus, morphine/oxycodone offers an attractive alternative to oxycodone/acetaminophen for the management of moderate to severe postoperative pain.

Tolerability and efficacy of two synergistic ratios of oral morphine and oxycodone combinations versus morphine in patients with chronic noncancer pain.

OBJECTIVES: Analgesic synergy and improved tolerability have been reported for flexible dose morphine and oxycodone combinations. This report describes two studies with similar double-blind, randomized, 7-day crossover designs (up to 7 days per arm) conducted to 1) explore the analgesic and safety benefit offixed ratio of morphine (M) and oxycodone (0) combinations (MOX) and 2) define the optimal ratio for morphine and oxycodone combination. SETTING: Clinical study centers in Australia. PATIENTS: Patients with chronic noncancer pain. INTERVENTION: Eligible patients were randomly assigned to receive flexible doses of either M or fixed ratio of MOX (M3:02 in study A; M1:02 in study B). The starting doses of M or MOX were the morphine equivalent doses (MEDs) converted from the analgesics received before entering double-blind treatment. At each crossover period, the doses were titrated to achieve analgesia at steady state, which was defined as when the same total daily dose (+/-10 percent) had been given consecutively for 3 days. MAIN OUTCOME MEASURE: The primary endpoint was the study medication dose (MED), which produced adequate pain control at steady state. RESULTS: Analgesic synergy in MOX was observed in both studies. On an MED basis, 61.6 percent (study A, M:0 = 3:2) or 46.8 percent (study B, M:0 = 1:2) more MED were needed forM monotherapy to achieve steady-state pain control when compared with MOX. Patient tolerability profiles were also generally better in the MOX groups. CONCLUSION: A 3:2 or 1:2 fixed ratio combination of morphine and oxycodone (MOX) produced analgesic synergy and a tolerability profile improvement in patients with chronic noncancer pain.

Analgesic efficacy and tolerability of intravenous morphine versus combined intravenous morphine and oxycodone in a 2-center, randomized, double-blind, pilot trial of patients with moderate to severe pain after total hip replacement.

BACKGROUND: Results from studies with a combination of oral morphine and oxycodone in postsurgical patients demonstrate significant analgesia and a tolerability profile comparable to other pain medications at morphine-equivalent doses. However, an intravenous (IV) combination has not previously been studied. OBJECTIVE: This study evaluated the efficacy and tolerability of IV morphine versus a combination of IV morphine and IV oxycodone in a 1:1 ratio. METHODS: This was a 2-center, randomized, double-blind, active-controlled pilot trial of 40 patients who had undergone total hip replacement. After surgery, when pain levels reached ≥4 (on the 11-point Numerical Pain Rating Scale), patients were randomized to 1 of 2 treatment groups. In part 1 of the study, patients were dosed every 5 minutes for the first 65 minutes (up to 13 doses) with study drug, provided that vital signs criteria were met. After an initial loading dose of either morphine 1.5 mg coadministered with oxycodone 1.5 mg or morphine 3 mg alone, patients received IV morphine 1.5 mg or IV morphine 0.75 mg/IV oxycodone 0.75 mg every 5 minutes. If patients achieved a pain score of 2 or experienced intolerable adverse events to drug when stable, they were permitted to enter part 2. In part 2, patients received blinded study medication (IV morphine plus IV oxycodone [0.5 mg/0.5 mg] or 1 mg IV morphine alone) via patient-controlled analgesia (PCA) for 47 hours. RESULTS: At baseline, treatment groups were comparable except for a higher proportion of females in the IV morphine group. Baseline pain intensity averaged 7 on the Numerical Pain Rating Scale of 0 to 10. One patient in the morphine group and 2 patients in the morphine/oxycodone group discontinued the study. The sum of the pain intensity differences from baseline to 65 minutes during the dose-titration phase was 1.8 for morphine alone versus 2.7 for morphine/oxycodone (P = 0.12); these values occurred at the same median number of doses (12) for each group. In part 2 (PCA dosing) of the study, similar levels of analgesia were achieved. During the study, 24% of the IV morphine/oxycodone group and 37% of the IV morphine group experienced nausea, and 10% of the IV morphine/oxycodone group and 16% of the IV morphine group had emesis. Two patients in the IV morphine/oxycodone group and 4 in the IV morphine alone group experienced oxygen desaturation. CONCLUSIONS: The combination of IV morphine and oxycodone provided pain relief with an acceptable tolerability profile in these patients experiencing moderate to severe postoperative pain. However, as an explorative pilot study, the power was not adequate to demonstrate statistical significance for differences between IV morphine/oxycodone and IV morphine alone. European Clinical Trials Data Base registration code: EudraCT-No. 2008-008527-14.

Analgesic and adverse effects of a fixed-ratio morphine-oxycodone combination (MoxDuo) in the treatment of postoperative pain.

OBJECTIVE: To compare efficacy and safety profiles of an immediate-release morphine and oxycodone Dual-Opioid combination (MoxDuo) versus its individual components and versus its morphine-equivalent doses in moderate to severe postoperative pain patients. DESIGN: Randomized, double-blind, 48-hour, parallel-treatment, multicenter, six-arm study of MoxDuo. SETTING: Six US centers. PATIENTS: Within 6 hours after bunionectomy surgery, patients were eligible if they reported pain intensity > or = 2 on the 4-point Likert scale and > or = 4 on an 11-point Numerical Pain Rating Scale (197 randomly assigned; 175 completers). INTERVENTIONS: MoxDuo 12 mg/8 mg, MoxDuo 6 mg/4 mg, morphine 12 mg, oxycodone 8 mg, morphine 6 mg, or oxycodone 4 mg (all administered q6h). MAIN OUTCOME MEASURE: Sum of pain intensity differences 0-24 hours after the first dose of study medication (SPID24) and percentage of patients with moderate to severe nausea, emesis, or dizziness. RESULTS: SPID24 was significantly better in the MoxDuo 12 mg/8 mg group when compared with its individual components (morphine 12 mg [p = 0.009] and oxycodone 8 mg [p = 0.037]), and when compared with MoxDuo 6 mg/4 mg (p = 0.011; 54.3 vs 28.5, 35.7, and 30.0, respectively). MoxDuo6 mg/4 mg and its morphine-equivalent doses (morphine 12 mg and oxycodone 8 mg) had comparable analgesic effects. There was a 50-75 percent reduction in moderate to severe adverse events (AEs) commonly associated with opioids (ie, nausea, vomiting, and dizziness) in the MoxDuo 6 mg/4 mg group when compared with its morphine-equivalent dose groups. CONCLUSIONS: MoxDuo produced superior analgesic effects when compared with its individual components, but comparable efficacy when compared with its morphine-equivalent doses. Common AEs were reduced at least 50 percent with MoxDuo when compared with its morphine-equivalent doses. MoxDuo may be an improved intervention in the management of moderate to severe acute pain.

A double-blind, placebo-controlled study of dual-opioid treatment with the combination of morphine plus oxycodone in patients with acute postoperative pain.

OBJECTIVE: animal and human studies suggest that coadministration of two opioids with different receptor binding properties may result in enhanced analgesia and fewer opioid-related adverse events (AEs). Q8003 (MoxDuo), an oral dual-opioid formulation with a fixed ratio (3:2) of morphine and oxycodone, was evaluated for analgesic effects and safety in the management of acute moderate to severe pain. DESIGN: randomized, double-blind, placebo-controlled, ascending-dose cohort, dose-response study with flexible dosing. SETTING: private clinic. PATIENTS: adults undergoing unilateral bunionectomy surgery. Following surgery, patients were required to have moderate or severe intensity pain on a 4-point Likert scale and >or= 4 on an 11-point Numerical Pain Rating Scale to continue in the study. INTERVENTIONS: Q8003 was administered in four ascending-dose cohorts of 3/2, 6/4, 12/8, and 18/12 mg during the 48-hour period following surgery. MAIN OUTCOME MEASURES: sum of the pain intensity differences from baseline over 48 hours (SPID48), percentage of responders, and use of ibuprofen. RESULTS: Of 263 patients, 256 were randomly assigned to treatment. In patients treated with Q8003, 12 to 18 percent withdrew before study completion versus 30 percent on placebo. The mean dose of morphine/oxycodone per 6-hour period and the mean interdose interval (hours) was 6/4 mg (2.9), 9.8/6.5 mg (4.1), 11/7.5 mg (6.8), and 15/10 mg (6.6) for the 3/2-, 6/4-, 12/8-, and 18/12-mg groups, respectively. The mean SPID48 was significantly greater with each Q8003 dose when compared with placebo (p - 0.0017 for all doses versus placebo). The 12/8-mg group (11/7.5 mg/6 h) had the greatest percentage of patient responders (76 percent; p < 0.001 versus placebo) and required the fewest daily doses of ibuprofen. AEs were typical of those associated with opioid use, with the highest occurrence for nausea (38-65 percent) and low rates of somnolence (2-8 percent). Minimal or no changes in respiration and blood oxygenation were observed and euphoria was not reported. CONCLUSIONS: the 12/8 mg dose of Q8003, an immediate-release formulation, provided the optimal combination of analgesic efficacy and tolerability, with the 3/2 and the 6/4 mg doses being an effective alternative for treatment.

Needle-free powder lidocaine delivery system provides rapid effective analgesia for venipuncture or cannulation pain in children: randomized, double-blind Comparison of Venipuncture and Venous Cannulation Pain After Fast-Onset Needle-Free Powder Lidocaine or Placebo Treatment trial.

OBJECTIVE: The Comparison of Venipuncture and Venous Cannulation Pain After Fast-Onset Needle-Free Powder Lidocaine or Placebo Treatment trial was a randomized, single-dose, double-blind, phase 3 study investigating whether a needle-free powder lidocaine delivery system (a sterile, prefilled, disposable system that delivers lidocaine powder into the epidermis) produces effective local analgesia within 1 to 3 minutes for venipuncture and peripheral venous cannulation procedures in children. METHODS: Pediatric patients (3-18 years of age) were randomly assigned to treatment with the needle-free powder lidocaine delivery system (0.5 mg of lidocaine and 21 +/- 1 bar of pressure; n = 292) or a sham placebo system (n = 287) at the antecubital fossa or the back of the hand 1 to 3 minutes before venipuncture or cannulation. All patients rated the administration comfort of the needle-free systems and the pain of the subsequent venous access procedures with the Wong-Baker Faces Pain Rating Scale (from 0 to 5). Patients 8 to 18 years of age also provided self-reports with a visual analog scale, and parents provided observational visual analog scale scores for their child's venous access pain. Safety also was assessed. RESULTS: Immediately after administration, mean Wong-Baker Faces scale scores were 0.54 and 0.24 in the active system and sham placebo system groups, respectively. After venipuncture or cannulation, mean Wong-Baker Faces scale scores were 1.77 +/- 0.09 and 2.10 +/- 0.09 and mean visual analog scale scores were 22.62 +/- 1.80 mm and 31.97 +/- 1.82 mm in the active system and sham placebo system groups, respectively. Parents' assessments of their child's procedural pain were also lower in the active system group (21.35 +/- 1.43 vs 28.67 +/- 1.66). Treatment-related adverse events were generally mild and resolved without sequelae. Erythema and petechiae were more frequent in the active system group. CONCLUSIONS: The needle-free powder lidocaine delivery system was well tolerated and produced significant analgesia within 1 to 3 minutes.

Controlled-release oxycodone for pain in diabetic neuropathy: a randomized controlled trial.

BACKGROUND AND OBJECTIVE: Opioid treatment has played a limited role in the management of diabetic neuropathy, in part because of concerns about the responsiveness of neuropathic pain to opioid treatment. This controlled study evaluated the efficacy and safety of controlled-release (CR) oxycodone in subjects with moderate to severe pain due to diabetic neuropathy. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study included 159 subjects with moderate to severe pain due to diabetic neuropathy. Treatment began with either one 10-mg tablet of CR oxycodone (n = 82) or identical placebo (n = 77) every 12 hours. Doses could be increased every 3 days to a maximum of 6 tablets (60 mg CR oxycodone) every 12 hours. Treatment lasted up to 6 weeks. The primary efficacy variable was overall average daily pain intensity during study days 28 to 42. RESULTS: At an average (SD) dose of 37 (21) mg per day (range 10 to 99 mg/d), CR oxycodone provided more analgesia than placebo (p= 0.002) in the intent-to-treat cohort. From days 28 to 42, overall average daily pain intensity (least squares mean +/-SE), rated in subject diaries on a numeric scale of 0 (no pain) to 10 (pain as bad as you can imagine), was 4.1 +/- 0.3 in subjects given CR oxycodone and 5.3 +/- 0.3 in placebo-treated subjects. Overall, 80 (96%) of 82 subjects given CR oxycodone and 52 (68%) of 77 subjects who received placebo reported adverse events. The most common adverse events in the CR oxycodone group were opioid related. CONCLUSIONS: In this 6-week trial, CR oxycodone was effective for the treatment of moderate to severe pain due to diabetic neuropathy. Adverse events were typical of opioid-related side effects.

A novel lectin, DltA, is required for expression of a full serum resistance phenotype in Haemophilus ducreyi.

Haemophilus ducreyi, the causative agent of chancroid, is highly resistant to the complement-mediated bactericidal activity of normal human serum (NHS). Previously, we identified DsrA (for ducreyi serum resistance A), a major factor required for expression of the serum resistance phenotype in H. ducreyi. We describe here a second outer membrane protein, DltA (for ducreyi lectin A), which also contributes to serum resistance in H. ducreyi. Isogenic dltA mutants, constructed in 35000HP wild-type and FX517 dsrA backgrounds, were more susceptible to the bactericidal effects of NHS than each respective parent, demonstrating the additive effect of the mutations. Furthermore, expression of dltA in H. influenzae strain Rd rendered this highly susceptible strain partially resistant to 5% NHS compared to a vector-control strain. Although primary basic local alignment search tool analysis of the dltA open reading frame revealed no close bacterial homologue, similarity to the beta-chain of the eukaryotic lectin ricin was noted. DltA shares highly conserved structural motifs with the ricin beta chain, such as cysteines and lectin-binding domains. To determine whether dltA was a lectin, ligand blots and affinity chromatography experiments were performed. DltA was affinity purified on immobilized lactose and N-acetylgalactosamine, and N-glycosylated but not glycosidase-treated model glycoproteins bound DltA. These data indicate that DltA is a lectin with specificity for lactose-related carbohydrates (CHO) and is important for H. ducreyi serum resistance.