Life-threatening infection with multiresistant Staphylococcus epidermidis in a patient with end-stage renal disease: cure with chloramphenicol and quinupristin/dalfopristin (RP 59500).

A 45-year-old man with end-stage renal disease underwent a cadaveric kidney transplantation. The allograft had to he removed 10 days after transplantation because of an acute vascular rejection. After explantation, the patient suffered from a life-threatening infection with Staphylococcus epidermidis involving lungs, eyes and liver for 11 months. Despite adequate therapy including vancomycin followed by teicoplanin, he developed spondylodiscitis requiring repeated surgical interventions. The definitive cure was achieved by a sequential therapy with chloramphenicol and quinupristin/dalfopristin.

Sulbactam in combination with mezlocillin, piperacillin or cefotaxime: clinical and bacteriological findings in the treatment of serious bacterial infections.

An open, multicentre study was performed in hospital in-patients at a total of 12 German hospitals to investigate the efficacy and tolerability of sulbactam combined with mezlocillin, piperacillin or cefotaxime in severe bacterial infections. A total of 155 patients were recruited into the study, of whom 48 were suffering from respiratory tract infections, 66 from intra-abdominal infections, 34 from skin/soft tissue infections including postoperative wound infections, and five from complicated urinary tract infections. Fifty-five patients intravenously received 4 g mezlocillin and 1 g sulbactam three times daily, 52 received 4 g piperacillin and 1 g sulbactam three times daily, and 48 received 2 g cefotaxime and 1 g sulbactam three times daily. The antibiotic and sulbactam combination was administered in all cases by rapid intravenous infusion of both components together, over 20 min. The mean duration of treatment was 20 days. The criteria used to define the outcome of treatment as successful were clinical cure (complete disappearance of the signs and symptoms of infection seen before the start of treatment) or improvement (appreciable diminution or partial resolution of the initial signs and symptoms, no further antibiotic therapy required) and the elimination of the organisms isolated before the start of the study. Of the 153 clinically evaluable patient, 141 (92%) were classed as responders (a cure was obtained in 98 cases and improvement in 43 cases). No response to the study medication was seen in 12 patients (7.8%). The response rates of the combined antibiotic-sulbactam preparations were 91% for mezlocillin/sulbactam, 92% for piperacillin/sulbactam, and 93% for cefotaxime/sulbactam. These response rates are almost identical. A total of 106 patients (68.4%) were bacteriologically evaluable; a total of 192 bacterial organisms were identified in these patients before the start of treatment. Mixed infection was present in 55 patients. The causative organism initially isolated was eliminated in 96 patients (90%), accounting for 180 of 192 strains (94%). Persistence of the causative organism (12 strains) was seen in eight patients (7.6%). Superinfection (four strains) was seen in two patients (1.9%). The study medication was well tolerated; adverse drug effects were seen in only five patients (3.3%). Treatment was discontinued in one patient because of the adverse effect (exanthema). The combination of the beta-lactamase inhibitor sulbactam and a ureidopenicillin or cefotaxime was highly effiacious in patients with severe bacterial infections investigated in this study. The availability of sulbactam as a single-agent preparation opens up new avenues for flexible and cost-effective antibiotic therapy and is a valuable contribution to the control of bacterial resistance.

Comparison of sulbactam/ampicillin and cefuroxime in infections of the lower respiratory tract: results of a prospective, randomized and comparative study.

In a randomized, prospective study, ampicillin (AMP) in combination with the beta-lactamase-inhibitor sulbactam (SBT) was compared with cefuroxime (CXM) in 73 hospitalized patients with lower respiratory tract infections. Of these patients 36 received SBT/AMP 1 g/2 g tid and 37 received CXM 1.5 g tid - both in the form of intravenous infusion. The duration of treatment ranged from 5 to 12 days, with a median of 8 days in each group. In the SBT/AMP group, 23 patients (64%) had pneumonia, while 13 (36%) had acute purulent bronchitis; 13 of the patients (36%) received artificial respiration. In the CXM group, 23 patients (62%) had pneumonia and 14 (38%) acute purulent bronchitis; eight patients (22%) required artificial respiration. In 54 patients (SBT/AMP: 26; CXM: 28), initial culture yielded bacterial pathogens, mainly Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus and pneumococci. In each group, 35 patients were clinically evaluable. Of the patients receiving SBT/AMP, 31 (89%) responded to treatment and 28 patients (80%) responded to treatment with CXM. Four patients (11%) who received SBT/AMP failed to respond, as did seven patients on CXM. The bacteriological efficacy was assessed in 26 patients in the SBT/AMP group: in 22 cases (84%) baseline pathogens were eradicated, while in two patients (8%), there was persistent infection and a superinfection, respectively. In 23 patients (82%) of the CXM group (28 patients evaluated), the pathogens were eradicated, while three cases (11%) had persistent infection, and two (7%) superinfection. Apart from a case of exanthema under CXM, no adverse drug reactions were reported. No statistically significant differences were seen between the two groups. SBT/AMP proved to be a safe and effective alternative to CXM in the treatment of lower respiratory tract infections in hospitalized patients.

Which antibiotic is better for the treatment of infections of the lower respiratory tract?

The efficacy and tolerance of mezlocillin and ampicillin/sulbactam were investigated in an open, comparative, multicentre study involving 96 patients. The high levels of efficacy of both ampicillin/sulbactam and mezlocillin, as previously documented in comprehensive in vitro studies, were confirmed with regard to the wide range of pathogens examined in this study. Both therapies were also associated with high clinical success rates and were well tolerated. It is worth noting that the larger number of patients suffering from chronically obstructive bronchitis apparently had no negative effects on the clinical results of the ampicillin/sulbactam therapy. In cases of nosocomial respiratory tract infections, especially those with a high incidence of beta-lactamase-producing organisms, a combination including beta-lactamase inhibitors may be expected to be superior to any of the ureido penicillins. The present study demonstrates that in cases of community acquired infections of the lower respiratory tract, treatment with ampicillin/sulbactam can be regarded as a suitable therapeutic alternative to mezlocillin, combining high efficacy and tolerance.

Concentrations of ampicillin and sulbactam in serum and in various compartments of the respiratory tract of patients.

After infusion of 2 g ampicillin and 1 g sulbactam the concentrations of these two beta-lactams were determined in serum and various compartments of the respiratory tract of 22 patients. About 30 min after the end of the infusion in 15 patients the mean serum concentration of ampicillin was 97 +/- 9.5 mg/l and of sulbactam 37.6 +/- 3.8 mg/l; in the biopsy samples of bronchial mucosa the concentration of ampicillin was 38.6 +/- 7.2 mg/kg and of sulbactam 28.1 +/- 5.2 mg/kg; in bronchial fluid the concentration of ampicillin was 0.6 +/- 0.1 mg/l and of sulbactam 0.3 +/- 0.1 mg/l (n = 15). In a further seven patients serum and pleural empyema samples were analysed and compared. The mean values of Cmax attained 1 to 2 h after the end of the infusion in pleural empyema were 7.6 +/- 3.1 mg/l and 6.2 +/- 1.6 mg/l for ampicillin and sulbactam, respectively. The two beta-lactams were eliminated markedly more slowly from empyema than from serum. These results show that ampicillin and sulbactam rapidly penetrate into various compartments of the respiratory tract and reach therapeutically active concentrations. The ratio of their concentrations (2:1) is largely the same as that in serum. The pharmacokinetic data therefore support the use of ampicillin/sulbactam in the perioperative prophylaxis and the treatment of bacterial infections of the lower respiratory tract.

Penetration of ampicillin and sulbactam into human costal cartilage.

The question of whether ampicillin and sulbactam are able to penetrate sufficiently into costal cartilage tissue was investigated in 21 children undergoing surgery for funnel chest malformations. The concentrations of both compounds were determined in the core and mantle pieces of samples taken 45 min or 120 min after infusion of ampicillin/sulbactam (33.3/16.7 mg/kg bodyweight) preoperatively for antibiotic prophylaxis. Ampicillin was determined by bioassay and sulbactam was determined by gas-chromatography/mass spectrometry. Mean concentrations of ampicillin were 23.3 mg/kg and 10.4 mg/kg at 45 min and at 27.4 mg/kg and 7.8 mg/kg 120 min in the mantle and core piece, respectively. Mean concentrations of sulbactam were at the same time 21.3 mg/kg and 9.7 mg/kg and 17.5 mg/kg and 11.9 mg/kg, respectively. These values indicate that both compounds achieve high concentrations even in bradytrophic tissue such as cartilage. The concentrations exceed the MIC values of important bacterial pathogens involved in postoperative wound infections. Therefore ampicillin protected by sulbactam appears to be a well-suited agent for perioperative prophylaxis in thoracic surgery.

[Sulbactam/ampicillin in comparison with cefuroxime for infections of the lower respiratory tract. Results of a prospective, randomized comparative study]. / Sulbactam/Ampicillin im Vergleich zu Cefuroxim bei Infektionen der unteren Atemwege. Ergebnisse einer prospektiven, randomisierten Vergleichsstudie.

In a randomized prospective study, ampicillin (AMP) in combination with the beta-lactamase-inhibitor, sulbactam (SBT) was compared with cefuroxime (CXM) in 73 hospitalized patients with lower respiratory tract infections. 36 patients received SBT/AMP 1 g/2 g t.i.d. and 37 patients received CXM 1.5 g t.i.d.--both in the form of i.v. infusion. The duration of treatment ranged from five to twelve days, with a median of eight days in each group. 23 patients (64%) of the SBT/AMP group had pneumonia, while 13 (36%) had acute purulent bronchitis; 13 of the patients (36%) received artificial respiration. 23 patients (62%) of the CXM group had pneumonia and 14 (38%) acute purulent bronchitis; eight patients (22%) required artificial respiration. In 54 patients (SBT/AMP: 26; CXM: 28) initial culture yielded bacterial pathogens, mainly Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus and pneumococci. 35 patients in each group were clinically evaluable. 31 patients (89%) responded to treatment with SBT/AMP, and 28 patients (80%) to treatment with CXM. Four patients (11%) who received SBT/AMP failed to respond, as did seven patients on CXM. The bacteriological efficacy was assessed in 26 patients of the SBT/AMP group: in 22 cases (84%) baseline pathogens were eradicated, while in two patients (8%) each, there was persistent infection and a superinfection, respectively. In 23 patients (82%) of the CXM group (28 patients evaluated) the pathogens were eradicated, while three cases (11%) had persistent infection, and two (7%) superinfection. Apart from a case of exanthema under CXM, no adverse drug reactions were reported. No statistically significant differences were to be seen between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Sulbactam in combination with mezlocillin, piperacillin or cefotaxime. Clinical and bacteriological results in the treatment of severe bacterial infections]. / Sulbactam in Kombination mit Mezlocillin, Piperacillin oder Cefotaxim. Klinische und bakteriologische Ergebnisse bei der Behandlung schwerer bakterieller Infektionen.

An open multicenter study on inpatients of 12 german hospitals was performed to investigate efficacy and safety of sulbactam in combination with mezlocillin, piperacillin or cefotaxim in severe bacterial infections. In total 155 patients were enrolled. The following infections were diagnosed: 48 lower respiratory tract infections, 66 intraabdominal infections, 34 skin/soft tissue infections including post operative wound infections and 5 complicated urinary tract infections. 55 patients received 3 daily doses of 4 g mezlocillin + 1 g sulbactam, 52 patients received 3 daily doses of 4 g piperacillin + 1 g sulbactam and 48 patients received 3 daily doses of 2 g cefotaxim + 1 g sulbactam. Antibiotics and sulbactam were administered concomitantly via intravenous short infusion. Mean duration of therapy was 8 days. Endpoints for assessment of therapeutic efficacy were cure (complete resolution of pretreatment signs and symptoms of the infection) or improvement (marked reduction or partial disappearance or pretreatment signs and symptoms, no further antibiotic therapy required) as well as eradication of pretreatment pathogens. 141 (92%) of 153 evaluable patients were successfully treated (98 cures and 43 improvements), therapy failed in 12 patients (7.8%). Success rates of the 3 sulbactam combinations were almost identical: 91% for mezlocillin/sulbactam, 92% for piperacillin/sulbactam and 93% for cefotaxim/sulbactam. 106 patients (68.4%) were also bacteriologically evaluable. In these patients 192 bacterial pathogens were isolated prior to study therapy, 55 patients had mixed infections. In 96 patients (90%) pretreatment pathogens were eradicated (180 strains = 94%).(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of ampicillin and sulbactam in patients undergoing heart surgery.

The pharmacokinetics of ampicillin and sulbactam, a new beta-lactamase inhibitor, were investigated in 16 patients undergoing prosthetic cardiac valve insertion. The combination of 2 g of ampicillin and 1 g of sulbactam was administered as perioperative prophylaxis intravenously over 3 to 6 days. Several serum pharmacokinetic parameters were similar for the two drugs after three intravenous doses were given to patients following surgery. The half-lives of elimination of ampicillin and sulbactam were 79 +/- 4.9 and 88 +/- 5.9 min, the volumes of distribution were 15.6 +/- 1.4 and 17.7 +/- 1.2 liters/70 kg, and the total plasma clearances were 144.4 +/- 14.5 and 147.2 +/- 14.5 ml/min, respectively. The peak concentrations of ampicillin and sulbactam in serum were calculated to be 134.3 +/- 1.3 and 58.3 +/- 1.2 micrograms/ml, respectively. Ampicillin and sulbactam rapidly penetrated from the blood into various tissues collected during heart surgery, such as sternum, pericardium, myocardium, and endocardium. The concentrations of ampicillin in tissue ranged from 17.8 +/- 9.9 to 50 +/- 29.5 micrograms/g, and those of sulbactam in tissue ranged from 8.8 +/- 6.2 to 19.6 +/- 10.1 micrograms/g. The concentrations of ampicillin and sulbactam in serum and tissue also apparently exceeded the MICs against most beta-lactamase-producing bacteria usually involved in postoperative wound infections and prosthetic valve endocarditis. The ratio of the two compounds was approximately 2:1 in serum and in the various tissues affected by the operation. The pharmacokinetics of ampicillin and sulbactam in serum and investigated tissues suggest that the combination of the two beta-lactams will be effective in the perioperative prophylaxis of patients undergoing heart surgery.

Concentrations of ampicillin and sulbactam in serum and tissues of patients undergoing ENT surgery.

2 g ampicillin and 1 g sulbactam were given by infusion to 24 patients who were to be operated on in the ENT region. About 1 hour later during the operation samples of serum and of various tissues were taken and analysed for ampicillin and sulbactam. The mean serum concentrations of ampicillin and sulbactam were 59.2 mg/l and 31.6 mg/l, respectively. At the same time the concentrations of the two drugs were usually lower in the tissues than in serum. About 1 hour after the infusion the mean tissue concentration of ampicillin was 33.5 mg/kg and of sulbactam 19.5 mg/kg. The results show that ampicillin and sulbactam penetrate within an hour into the different tissues affected by the operation and maintain about the same ratio as in serum (2:1). The concentrations of ampicillin and sulbactam measured in the different compartments are capable of inhibiting the bacteria most frequently involved in ENT infections. These measurements unequivocally support the use of the ampicillin/sulbactam combination in the treatment and perioperative prophylaxis of bacterial infections of the ENT tract.

[Clinical results with sulbactam/ampicillin in a multicenter study of 425 patients]. / Klinische Ergebnisse mit Sulbactam/Ampicillin in einer multizentrischen Studie an 425 Patienten.

In an open, non-comparative multicenter study, efficacy and toleration of sulbactam/ampicillin for therapy of various infections were investigated. 42 centers in the Federal Republic of Germany and West-Berlin participated in this study. In total, 425 patients were included, 112 of whom suffered from renal/urinary tract infections, 103 from respiratory tract infections, 84 from intraabdominal infections, and 73 from skin/soft tissue infections. Moreover, 43 female patients had gynecological infections. More than 95% of the patients received three daily dosages of 3 g sulbactam/ampicillin via intravenous short-infusion. Mean duration of therapy was 7.3 days. In 280 patients, in total, pathogens were initially identified, among them were 87 patients with mixed infections. At study onset, 393 pathogens were identified, after completion of the trial 63 germs could still be made evident. In 234 cases (= 83.6%) pathogens were eradicated by therapy, in 19 patients superinfection occurred, and in 27 patients pathogenic organisms persisted. 419 patients were included into evaluation of clinical efficacy of sulbactam/ampicillin therapy. In 391 cases (= 93.3%) therapy was successful with 293 patients cured and 98 improved. Therapy failed in 28 patients (= 6.7%) which, in 23 cases, led to discontinuation of treatment. Sulbactam/ampicillin was well tolerated. In total, 55 adverse drug reactions were observed, 22 of which were exanthemas (= 5.2% of all patients). In seven patients (= 1.6%) therapy had to be discontinued due to adverse events. The combination of sulbactam, a beta-lactamase inhibitor, with the reliable antibiotic agent ampicillin has proved to be successful in therapy of infections of different localizations with excellent toleration.