Efficacy and safety of azithromycin versus benzylpenicillin or erythromycin in community-acquired pneumonia

Azithromycin, a recently introduced antibiotic, offers the potential advantages of short-course administration and lower toxicity compared to other macrolides. Approved for the treatment of mild pneumonia, this drug was investigated in a study of patients hospitalized for community-acquired pneumonia. In an open-labelled randomized study, oral azithromycin was compared with intravenous benzylpenicillin in patients suspected to have pneumonococcal pneumonia. Azithromycin was also compared with erythromycin, both administered orally, in all other patients. Three hundred thirty-four patients with community-acquired pneumonia were hospitalized, 108 of whom were randomized; 104 could be evaluated. A need for intravenous therapy was the most common reason for exclusion. In the pneumococcal group, 35 patients received azithromycin and 29 benzylpenicillin. The clinical and radiological success rate achieved with azithromycin (83 %) was considerably higher than that achieved with benzylpenicillin (66 %), though the difference was not significant. In the non-pneumococcal group, 19 patients received azithromycin and 21 erythromycin; no differences in the success rate were found (79 % and 76 %, respectively). Eight patients on azithromycin had a blood culture positive forStreptococcus pneumoniae; in three of these patients therapy was changed. None of the five patients with pneumococcal bacteraemia who received benzylpenicillin required a change in therapy. It is concluded that oral azithromycin, administered as short-course therapy, is an appropriate antibiotic for treating patients with community-acquired pneumonia. However, it is not yet certain that azithromycin is a good choice for patients with pneumococcal bacteraemia.     

Clarithromycin versus amoxicillin-clavulanic acid in the treatment of community-acquired pneumonia

In an open, prospective, randomised study, the clinical and bacteriological efficacy of intravenously administered clarithromycin was compared with that of amoxicillin-clavulanic acid in 112 patients with community-acquired pneumonia requiring hospitalisation. Clinical cure or improvement occurred in 86% (48/56) of the clarithromycin-treated patients and 84% (47/56) of the amoxicillin-clavulanic acid-treated patients. The rate of bacteriologie eradication was similar for the two drugs as were the rapidity of a clinical response and the rate of improvement of radiological signs. Clarithromycin had a slightly higher rate of side-effects mainly due to phlebitis caused by the intravenous treatment, but treatment could be continued in all cases. Clarithromycin should be used with caution in patients being treated with digoxin because of a significant risk of bradycardia resulting from drug interaction.     

Penicillin G/ofloxacin versus erythromycin/amoxicillin-clavulanate in the treatment of severe community-acquired pneumonia

In a prospective, randomized, multicenter trial, the efficacy of penicillin plus ofloxacin was compared to that of amoxicillin-clavulanate plus erythromycin in the treatment of community-acquired pneumonia. One hundred seventeen hospitalized patients presenting with severe community-acquired pneumonia received either penicillin 3 × 10⁶ U/6 h plus ofloxacin 200 mg twice daily (group A) or amoxicillin-clavulanate 1 g/6 h plus erythromycin 1 g/8 h (group B). Initial assessment included clinical examination, determination of simplified acute physiology score (SAPS), chest X-ray and evaluation of microbiological data obtained from blood, sputum and/or bronchoscopy. Follow-up was documented at 72 h and at 30 days. Both groups were comparable for age, sex, SAPS, chest X-ray, hypoxemia and microbiological data. The causative pathogen was identified in 54 cases (53 %),Streptococcus pneumoniae being most frequent isolate (54.7 %). All organisms cultured were susceptible to at least one of the antibiotics of each combination of the protocol, with the exception of two strains ofPseudomonas aeruginosa. A favorable outcome was observed in 76 % of the patients, equally distributed between the two groups. After completion of therapy there were 12 clinical failures in each group (20.5 %). Six patients in each group (10.3 %) died of infection. Tolerance was similar for both regimens, apart from an increased rate of superficial thrombophlebitis in patients receiving intravenous erythromycin. The combination of penicillin with ofloxacin is as effective and as safe as a previously recommended regimen combining amoxicillin-clavulanate and erythromycin in treating patients with community-acquired pneumonia.     

Trovafloxacin versus amoxicillin/clavulanic acid in the treatment of acute exacerbations of chronic obstructive bronchitis

Treatments with once-daily trovafloxacin (200 or 100 mg) and amoxicillin/ clavulanic acid (500/125 mg three times daily) were compared in adults with acute exacerbations of chronic obstructive bronchitis. At end of treatment, 95% (113/119) of clinically evaluable patients receiving trovafloxacin 200 mg, 98% (113/115) of patients treated with trovafloxacin 100 mg and 97% (113/117) of patients receiving amoxicillin/clavulanic acid were cured or improved. At study end, 91%, 87% and 88%, respectively, were cured or improved. At end of treatment, trovafloxacin 200 mg eradicatedHaemophilus influenzae in 97% of patients,Streptococcus pneumoniae in 90% andChlamydia pneumoniae in 100%. The respective eradication rates for trovafloxacin 100 mg were 84%, 100% and 100%; those for amoxicillin/ clavulanic acid were 92%, 100% and 100%. At study end, trovafloxacin 200 mg totally eradicated all three pathogens. Trovafloxacin 100 mg eradicatedHaemophilus influenzae in 91% of patients,Streptococcus pneumoniae in 100% andChlamydia pneumoniae in 80%. Respective eradication rates for amoxicillin/clavulanic acid were 78%, 100% and 80%. Only 7% (10/144) of patients receiving trovafloxacin 200 mg reported treatment-related adverse events, as did 7% (10/135) of patients given trovafloxacin 100 mg and 12% (17/140) of patients given amoxicillin/clavulanic acid.     

Cefdinir versus amoxicillin/clavulanic acid in the treatment of suppurative acute otitis media in children

An investigator-blinded, randomized, multicenter study was conducted to compare the efficacy and safety of cefdinir and amoxicillin/clavulanate (amoxicillin/CA) in the treatment of pediatric patients with acute suppurative otitis media. Patients 6 months to 12 years of age were randomized in a 111 ratio to receive cefdinir 14 mg/kg once-daily, cefdinir 7 mg/kg b.i.d., or amoxicillin/CA 13.3 mg/kg t.i.d. Test-of-cure was determined 11 to 16 days post therapy. Of the 752 patients who entered the study, 665 (88%) completed treatment and 595 (79%) were evaluable. Response rates in the three treatment groups were similar. Overall rates of adverse events were statistically lower in the cefdinir once-daily group than in the amoxicillin/CA group. Diarrhea was the most common adverse event in all treatment groups. Cefdinir given either once-daily or twicedaily is a safe and effective treatment for pediatric patients with acute suppurative otitis media.     

Cefuroxime and cefuroxime axetil versus amoxicillin plus clavulanic acid in the treatment of lower respiratory tract infections

In a large multinational study, the clinical and bacteriological efficacy of intravenous cefuroxime 750 mg t.i.d. followed by oral cefuroxime axetil 500 mg b.i.d. was compared to that of amoxicillin plus clavulanic acid (CA) administered as 1.2 g intravenously t.i.d. followed by 625 mg orally t.i.d. in the treatment of lower respiratory tract infections in hospitalised patients. A total of 512 patients were entered (256 in each treatment group). All were suffering from pneumonia or acute exacerbations of chronic bronchitis or bronchiectasis and required initial parenteral antibiotic therapy. Parenteral therapy lasted 48 to 72 h and was followed by five days of oral therapy. The clinical responses in the two treatment groups were very similar: 223 of 256 (87.1 %) patients were cured or improved with cefuroxime/cefuroxime axetil compared to 220 of 256 (85.9 %) with amoxicillin/CA. Positive pre-treatment sputum samples were obtained from 44 % of the patients. Clearance rates obtained were again similar: 72.8 % with cefuroxime/cefuroxime axetil and 70 % with amoxicillin/CA. Ten percent of the isolates were beta-lactamase producers, similar numbers of which were cleared in both groups. Both regimens were generally well tolerated, with only 5 % of patients treated with the cefuroxime regimen and 4.3 % of patients treated with amoxicillin/CA experiencing drug-related adverse events. Cefuroxime/cefuroxime axetil follow-on therapy produces clinical and bacteriological efficacy equivalent to that of amoxicillin/CA, with the advantage of twice daily oral administration.     

Trovafloxacin versus high-dose amoxicillin (1 g three times daily) in the treatment of community-acquired bacterial pneumonia

Once-daily trovafloxacin 200 mg was compared with high-dose amoxicillin, 1 g three times daily, given for 7 to 10 days. At end of treatment (day 10), the response was clinically successful (cure + improvement) in 93% of 152 clinically evaluable trovafloxacin patients and in 89% of 160 amoxicillin patients. At study end (day 35), respective rates were 91% and 81% (95% confidence interval: 1.6, 17.6; P=0.01). In evaluable patients with positive baseline radiographs, 93% of trovafloxacin and 88% of amoxicillin patients demonstrated radiological resolution at end of treatment.Streptococcus pneumoniae andHaemophilus influenzae eradication rates were comparable at end of treatment in both treatment groups, but at study endStreptococcus pneumoniae eradication rates were higher in trovafloxacin patients (100% vs 81%). At study end, all four trovafloxacin patients with baseline penicillinresistantStreptococcus pneumoniae were clinically cured with pathogen eradication, whereas two of five amoxicillin patients with baseline penicillin-resistantStreptococcus pneumoniae were clinical failures with pathogen persistence. For patients in whom no pathogen was identified, trovafloxacin was significantly more effective at end of treatment (P=0.096) and study end (P=0.013). Treatment-related adverse events were comparable; the most common were headache, vomiting and dizziness in trovafloxacin patients, and diarrhoea, headache and abdominal pain in amoxicillin patients.     

Initial empiric antibiotic therapy for community-acquired pneumonia in Chinese hospitals

ObjectivesStudies on treatment of community-acquired pneumonia (CAP) in China are scarce. We performed a study to investigate empiric antibiotic practices for patients hospitalized with CAP in China and the risk factors for treatment failure.MethodsData were collected from a national Chinese hospitalization database. Adult patients who were diagnosed with CAP between 1 October 2014 and 30 September 2015 were identified. We studied initial empiric antibiotic regimens, microbiologic sampling, treatment failure, in-hospital mortality and length of hospital stay.ResultsWe included 18 043 adult patients from 185 hospitals who met all the study inclusion criteria. The most common initial antibiotic regimen for CAP was monotherapy with a fluoroquinolone (14.8%, 2671/18 043). The most common initial antibiotic (used alone or in combination with other antibiotics) was levofloxacin (15.7%, 4597/29 278 (this denominator represents the total number of initial antibiotics)). The microbiologic sampling rate was 26.9% (4851/18 043). A total of 4050 (22.4%) of 18 043 patients experienced treatment failure. Multivariate logistic regression demonstrated that older age, male sex, coexisting lung cancer and use of regimens not covering atypical pathogens were risk factors for treatment failure. In-hospital mortality was 2.1% (380/18 043). The median hospital length of stay was 11 days (interquartile range, 8–15 days).ConclusionsPatients receiving Chinese guideline-adherent regimens had better outcomes, and atypical pathogen active regimens were associated with a lower treatment failure rate and shorter length of hospital stay.     

Comparative study of levofloxacin and amoxycillin/clavulanic acid in adults with mild-to-moderate community-acquired pneumonia

Objective: To compare the efficacy and safety of two different doses of levofloxacin with amoxycillin/clavulanic acid in the treatment of community-acquired pneumonia.
Methods: A double-blind, randomized (1:1:1), double-dummy, three-arm parallel design, multicenter study was conducted in adult patients with mild-to-moderate community-acquired pneumonia. In total, 518 patients were randomized to receive levofloxacin 500 mg once daily, levofloxacin 500 mg twice daily or amoxycillin/clavulanic acid 625 mg three times daily for 7–10 days.
Results: The clinical cure rates post-therapy (2–5 days after the end of treatment) in the intent-to-treat population were 84.2% (144/171) in the levofloxacin once-daily group, 80.2% (142/177) in the levofloxacin twice-daily group and 85.7% (144/168) in the amoxycillin/clavulanic acid group. In the per-protocol population, the clinical cure rates post-therapy were 95.2% (138/145), 93.8% (137/146) and 95.3% (141/148), respectively. The total pathogen eradication rates were 97.8%, 100% and 97.5%, respectively. Both drugs were equally well tolerated and no major adverse events were observed.
Conclusions: Levofloxacin was effective, safe and well tolerated in the treatment of mild-to-moderate community-acquired pneumonia. A complementary analysis indicated that there was no difference in therapeutic outcome between levofloxacin 500 mg once daily and twice daily. Levofloxacin 500 mg once daily, for 7–10 days, is an effective and safe treatment for mild-to-moderate community-acquired pneumonia in adults.     

Effect of clavulanic acid and/or polymorphonuclear neutrophils on amoxicillin bactericidal activity againstStreptococcus pneumoniae

The effects of polymorphonuclear neutrophils (PMNs) and/or clavulanic acid on the bactericidal activity of amoxicillin (at human serum achievable concentrations) against a serotype 3 penicillin-susceptibleStreptococcus pneumoniae strain [minimal inhibitory concentration /minimal bactericidal concentration (MIC/MBC) values of penicillin, amoxicillin, and amoxicillin/clavulanic acid (2:1)=0.01/0.01 g/ml] and a serotype 9 penicillin-resistant strain [MIC/MBC of penicillin, amoxicillin, and amoxicillin/clavulanic acid (2:1)=1/2 g/ml] were studied. Against the penicillin-resistant strain, subinhibitory concentrations of amoxicillin reduced the growth rate; this effect was increased by the addition of clavulanic acid. A reduction of the penicillin-resistant initial inocula (3 × 10⁶ cfu/ml) at subinhibitory concentrations was obtained only with amoxicillin plus clavulanic acid and PMNs. At suprainhibitory concentrations, both clavulanic acid and PMNs increased the bactericidal activity of amoxicillin, as evidenced by an increased reduction in the penicillin-resistant initial inocula. The combined effect of these antibiotics and immune defenses may help explain the maintenance of their clinical efficacy in respiratory tract infections, despite the increase in the incidence of penicillin-resistant pneumococci.     

Ceftriaxone versus ampicillin for the treatment of community-acquired pneumonia. A propensity matched cohort study

ObjectivesCeftriaxone is recommended as first-line antibiotic treatment (with the addition of macrolide) for hospitalised adults with community acquired pneumonia (CAP). Narrower-spectrum β-lactam as ampicillin, may be associated with comparable clinical outcomes, with less emergence of resistant pathogens or Clostridioides difficile infection (CDI). We aimed to examine whether ampicillin and ceftriaxone (with the addition of macrolides for both arms) are comparable for the treatment of hospitalized adults due to CAP.MethodsThis was a single center, observational cohort study. We included adult patients who were hospitalized in internal medicine wards due to CAP and were treated with either ceftriaxone or ampicillin with the addition of macrolide. A propensity-score model was used. The primary outcome was 30-day all-cause mortality. A multivariable logistic regression analysis and Kaplan-Meier survival analysis was performed. We performed subgroup analyses for the main outcome based on CURB-65 score and age.ResultsA total of 1586 patients fulfilled the inclusion criteria. There was no difference in 30-day mortality rate in the total cohort (28/233 vs. 208/1353 in ampicillin and ceftriaxone arm, respectively; p = 0.184). In the propensity matched cohort (197 in ampicillin and 394 in ceftriaxone arm), there was no significant difference in 30-day all-cause mortality between treatment groups in multivariable analysis of the main model (OR 0.67, 95% CI, 0.37–1.2; p = 0.189) and Kaplan-Meier survival analysis (p = 0.108). Thirty-day mortality rate was (19/197 vs. 57/394, in ampicillin and ceftriaxone arms, respectively; p = 0.108) Patients who were treated with ampicillin experienced significantly lower rates of CDI (0/197, 0% vs. 8/394, 2%; p = 0.044).DiscussionAmpicillin was associated with comparable clinical outcomes in comparison to ceftriaxone for patients who were hospitalized due to CAP. Ampicillin was associated with significantly lower rate of CDI. Results need to be confirmed by more robust study designs.     

Cefaclor versus amoxicillin in the treatment of bacterial pneumonia: A comparative double-blind study

A randomized double-blind controlled trial was carried out to compare the effectiveness and side-effects of cefaclor with those of amoxicillin in the treatment of 34 patients hospitalized because of acute bacterial pulmonary infection. Cefaclor and amoxicillin were given three times daily before meals in a dosage of 500 and 750 mg respectively for seven days. The cure rate was 94 % in the group of patients treated with cefaclor and 89 % in the group treated with amoxicillin. According to all the parameters used to assess outcome, no significant difference was found between the two antibiotics tested. In this study, cefaclor and amoxicillin appeared to be of equal value in the treatment of bacterial pneumonia or bronchopneumonia.     

Comparative study of azithromycin and amoxicillin/clavulanic acid in the treatment of lower respiratory tract infections

Forty-eight patients with acute bronchitis and four with pneumonia were randomly assigned to receive five doses (500 mg on day 1, plus 250 mg/day on days 2–5) of azithromycin; 54 patients with acute bronchitis and four with pneumonia were assigned 30 doses (625 mg every eight hours for ten days) of amoxicillin/clavulanic acid (CA). The two regimens were equally effective, with clinical improvement or cure in 92 % and 87 % of patients respectively, bacteriological cure in 89 % and 86 %, with 91 % and 89 % of pathogens eliminated. Minor side effects occurred in 6 % and 12 % of patients in the two groups, respectively. No major abnormalities in laboratory safety parameters were seen in either group.     

Influence of amoxicillin combined with clavulanic acid on the fecal flora in children

The effect of an amoxycillin-clavulanic acid combination on the intestinal bacterial ecosystem was studied by differential quantitative analysis of the fecal flora in 11 hospitalized pediatric patients aged 8 months to 4 years. The antibiotic combination was given orally to 7 patients and intravenously to 4. The modifications in the intestinal flora are more important with oral route than intravenous route. After treatment, an increase in ampicillin-resistant E. coli with overgrowth of Klebsiella were found. Our previous studies have shown that this microbial overgrowth carries a risk of secondary septicemia. A strain of amoxycillin-resistant Serratia marcescens emerged but did not pullulate . The other aerobic or anaerobic bacteria were not significantly modified. Most strains which emerged after therapy remained susceptible to the combination. Yeasts emerged in two patients. Thus, the amoxycillin-clavulanic acid combination results in intestinal Klebsiella overgrowth, requiring monitoring of the intestinal bacterial ecosystem.     

Multicenter, randomized, double-blind comparison of erythromycin estolate versus amoxicillin for the treatment of acute otitis media in children

Erythromycin is frequently prescribed in Germany for acute otitis media, but well-designed clinical trials under present epidemiological conditions are lacking. Therefore, a double-blind, randomized, multicenter trial was performed to compare the clinical efficacy and safety of erythromycin estolate versus amoxicillin in children with acute otitis media and to identify the risk factors associated with clinical failure. Investigators from 19 centers throughout Germany recruited 302 children with clinical, otoscopic, and tympanometric evidence of acute otitis media. In a double-blind fashion, patients were allocated randomly to a 10-day course of erythromycin estolate at 40 mg/kg/day in two divided doses or amoxicillin at 50 mg/kg/day in two divided doses. Clinical examinations, otoscopy, and tympanometry were performed at baseline, day 3–5, day 9–11, and at 5 weeks. Clinical outcome was assessed on day 9–11. Two-hundred eighty children were evaluable for efficacy (erythromycin group, 141; amoxicillin group, 139). Both groups were comparable with respect to demographic data and severity of disease at entry. Treatment was successful in 94% of the erythromycin-treated patients and in 96% of the amoxicillin-treated patients. Clinical outcome was statistically equivalent between groups within a range of 7 percentage points. Clinical recurrence was seen in eight erythromycin-treated children (5.7%) and in seven amoxicillin-treated children (5.0%) (P=0.81). Patients with bilateral disease at entry were at higher risk of unfavourable outcome, whereas age and presence/absence of otorrhea at entry were not associated with outcome. Treatment-related adverse events were recorded in eight (5.3%) of 151 erythromycin-treated patients and in 11 (7.3%) of 151 amoxicillin-treated patients. In this study in an outpatient setting in Germany, erythromycin estolate was as safe and effective as amoxicillin in the treatment of acute otitis media. Both drugs can be administered in a convenient twice-daily dosage schedule.     

In vitro activity of amoxicillin plus clavulanic acid againstHaemophilus influenzae andBranhamella catarrhalis

The in vitro activity of amoxicillin in the presence of clavulanic acid against clinical isolates of Haemophilus influenzae and Branhamella catarrhalis was assessed in comparison with ampicillin, amoxicillin, cefaclor and erythromycin. The isolates were selected so as to yield equal numbers of beta-lactamase producing and non-beta-lactamase producing strains of the two species. MICs obtained by agar dilution indicated that amoxicillin in the presence of clavulanic acid was the most active of the drugs tested. Clavulanic acid potentiated the activity of amoxicillin against beta-lactamase-producing strains of both Haemophilus influenzae and Branhamella catarrhalis.Further studies on a few strains of each species revealed that the beta-lactamase of Haemophilus influenzae (TEM-1) rapidly inactivated ampicillin and slowly inactivated cefaclor but not cefuroxime. The Branhamella catarrhalis enzyme rapidly inactivated cefaclor, ampicillin and to some extent cefuroxime. Clavulanic acid afforded protection against the beta-lactamase action of both species when beta-lactam antibiotics were added to bacterial cultures.     

Clinical and microbiological efficacy of moxifloxacin versus amoxicillin/clavulanic acid in severe odontogenic abscesses: a pilot study

The aim of this study targeted the evaluation of the in vivo effect of moxifloxacin in the treatment of patients with severe odontogenic abscesses. This was a prospective, two-armed, randomised, unblinded, monocentric pilot study, which enrolled 21 hospitalized patients with severe odontogenic abscesses. After extraoral incision, patients were either treated with moxifloxacin 400 mg i.v. once daily or amoxicillin/clavulanic acid 2.2 g i.v. three times daily. Primary clinical endpoint was the time until clinical remission, represented by simultaneous assertion of the following criteria: body temperature <38.5°C, no pain at palpation, and mouth opening similar or better than preoperatively. White blood cell count, C-reactive protein, pain, health related quality of life (HR-QoL) and length of hospital stay were recorded as secondary outcome criteria. The mean duration until reaching the primary end point was 6.6 (range, 4.3–8.8) days in the moxifloxacin group and 6.0 (range, 3.8–8.2) days in the amoxicillin/clavulanic acid group. Median days of in-house treatment ranged between five and six days for both groups. HR-QoL was highly impaired in both groups preoperatively and reached near normal on days three and four in both samples. In this pilot investigation, moxifloxacin showed promising results as compared to amoxicillin/clavulanic acid. Therefore, a larger prospective clinical trial using moxifloxacin in severe odontogenic abscesses appears encouraging. We suggest a combination of body temperature, palpatory pain, and subjective pain as a parameter for successful intervention; however, both findings need prospective validation by means of a phase III evaluation.     

Bactericidal effect of cefadroxil, amoxicillin alone or in combination with clavulanic acid in sera of healthy volunteers]

Determination of minimal inhibitory concentrations (MICs) provides data on the susceptibility or resistance of a bacteria; however, in susceptible bacteria this parameter is not predictive of effectiveness of the antimicrobial agent. Bactericidal activities of cefadroxil, of amoxicillin, and of the amoxicillin-clavulanic acid combination on bacteria commonly found in ENT and lower respiratory tract disease were studied comparatively. The antibiotics were given by the oral route to six healthy volunteers. With beta-lactamase-producing and non-beta-lactamase-producing strains of Escherichia coli, amoxicillin produced MICs consistent with susceptibility but failed to exhibit a bactericidal effect, whereas cefadroxil was bactericidal. Combination of amoxicillin with an inhibitor did not modify this activity on E. coli and failed to produce a bactericidal effect on Klebsiella pneumoniae similar to that seen with cefadroxil. Amoxicillin with and without clavulanic acid exhibited comparable effectiveness on Streptococcus pyogenes and S. Pneumoniae. The bactericidal effect of cefadroxil on S. pneumoniae was of similar magnitude but shorter duration than that of amoxicillin. Cefadroxil and the amoxicillin-clavulanic acid combination had similar bactericidal effects against Staphylococcus aureus. These antibiotics exhibited a time-dependent effect on Gram positive microorganisms. These pharmacodynamic data, together with measures of bactericidal activity, may be very helpful for selecting the appropriate antibiotic and dosage.