Clinical efficacy of tigecycline used as monotherapy or in combination regimens for complicated infections with documented involvement of multiresistant bacteria.

INTRODUCTION: Tigecycline is an established treatment option for infections with multiresistant bacteria (MRB). It retains activity against many strains with limited susceptibility to other antibiotics. Efficacy and safety of tigecycline as monotherapy or in combination regimens were investigated in a prospective noninterventional study involving 1,025 severely ill patients in clinical routine at 137 German hospitals. MATERIALS AND METHODS: Data on the full population have been published; our present analysis focuses on infections caused by MRB. The study population included patients with complicated infections, high disease severity (APACHE II > 15: 65 %) and high MRB prevalence. Most patients had comorbidities, including cardiovascular disease, renal insufficiency, and/or diabetes mellitus. Treatment success was defined as cure/improvement without requirement of further antibiotic therapy. RESULTS: Pathogens isolated from 215 evaluable patients with documented MRB infections included 132 methicillin-resistant Staphylococcus aureus (MRSA), 42 vancomycin-resistant Enterococci (VRE) and 67 Gram-negative extended beta-lactamase (ESBL) producers. Of the MRB subpopulation, 140 patients received tigecycline monotherapy, 75 were treated with combination regimens. High overall clinical success rates were recorded for MRB infections treated with tigecycline alone (94 %) or in combinations (88 %); in detail intraabdominal infections (monotherapy: 90 %; combinations: 93 %), skin/soft tissue infections (93; 100 %), community-acquired pneumonia (100; 100 %), hospital-acquired pneumonia (94,7; 72,7 %), diabetic foot infections (89; 33 %), blood stream infections (100; 100 %) and multiple-site infections (92; 71 %). CONCLUSIONS: Tigecycline achieved high clinical success rates in patients with documented infections involving MRB strains despite high disease severity. These results add to the evidence indicating that tigecycline is a valuable therapeutic option for complicated infections in severely ill patients with a high likelihood of multidrug-resistant pathogen involvement.

[Is monotherapy with ß-lactam antibiotics still up to date? New aspects for treatment of severe infections]. / Sind Monotherapien mit ß-Laktamantibiotika noch zeitgemäss?

Mortality of sepsis is still high. Crucial for therapeutic response are the early start of treatment as well as the choice of antibiotics or antibiotic combinations. ß-lactam antibiotics with bactericidal mode of action are often recommended in guidelines. But this antibiotic class can trigger the immune system to a maximum by releasing cell wall components or exotoxins. This may lead to a worsening of the patient's clinical situation. In contrast, antibiotics with bacteriostatic action often inhibit bacterial protein synthesis with decrease of production of virulence factors and minimize release of cell wall components. The purpose of this review is to summarise the significance of some bacteriostatic antibiotics and to discuss whether a combination of bactericidal and bacteriostatic agents may improve the course of the illness.

Urinary tract infection in men.

OBJECTIVE: To explore the prevalence and microbiology of urinary tract infection (UTI) in symptomatic men in a primary care setting and to determine the appropriateness of patient management of these conditions by the general practitioners. METHODS: A cross-sectional survey was carried out matching documentation of symptoms and management with urine culture and results of susceptibility tests. All patients presenting with symptoms typical for a UTI in 36 teaching general practices in the area of Göttingen, Germany, were eligible for enrolment in the study. 15% (n = 90) of all patients were adult men. General practitioners (GPs) were instructed to manage patients as usual. Patient characteristics, dipstick tests and treatment were matched with results of urine cultures and susceptibility testing. RESULTS: Men presenting with symptoms indicative of UTI were predominantly elderly (median age 61 years) and 41% had additional risk factors. Antibiotics were prescribed for 36%, but these were not well-targeted. Urine culture revealed UTI in 60%, of which half had low colony counts (23% of all patients) or multiple bacterial growth (7%); 40% had sterile urine. Dipstick tests proved unhelpful: leukocytes and nitrite had sensitivities of 54% and 38%, specificities of 55% and 84%, positive predictive values of 65% and 78% and negative predictive values of 44% and 46%, respectively. Resistance levels were 53% for amoxicillin and cefaclor, 28% for cefixim, 22% for ciprofloxacin, 34% for both trimethoprim as individual substance and the combination with sulfamethoxazole (cotrimoxazole) and 25% for nitrofurantoin. CONCLUSION: Men with symptoms indicative of a UTI should not be treated empirically. A urine culture and antibiogram should be obtained before a treatment decision is made. A low-count UTI was common and should not be considered normal.

[Puerperal sepsis caused by streptococcus group A with a severe form of progression like "toxic shock-like syndrome"]. / Puerperalsepis durch Streptokokken der Gruppe A mit schwerer Verlaufsform als "Toxic Shock-like Syndrome".

HISTORY AND CLINICAL FINDINGS: A previously healthy 32-year-old woman was admitted with shock symptoms 5 days after an uneventful home delivery. She developed a fever up to 39.5 degrees C during the days after delivery with sore throat, diarrhoea and muscle aches in all limbs. On physical examination there were swellings of the arms and lower legs as well as macular and vesicular erythrodermia, especially of the trunk. INVESTIGATIONS: Abnormal laboratory findings were thrombocytopenia (20,000/microliters), increased serum concentrations of fibrin breakdown products (102 mg/dl) and of C-reactive protein (> 200 mg/dl), increased creatine kinase (5700 U/l), transaminases (GOT 220 U/l, GPT 52 U/l), creatinine (2.0 mg/dl) and urea (114 mg/dl). Streptococcus pyogenes was grown on blood culture and from vaginal smear. Sonography, echocardiography and radiological examinations failed to demonstrate a septic focus. TREATMENT AND COURSE: Mechanical ventilation was required for 7 days because of respiratory failure and shock symptoms (toxic shock-like syndrome, TSLS). Penicillin G and tobramycin were given after the bacteriological diagnosis. Severe consumption coagulopathy was successfully treated with antithrombin III and platelet concentrates. After extubation she was found to have a flaccid tetraparesis, especially of the right and of the legs, due to soft-tissue necrosis and damage to peripheral nerves. An embolic occlusion of the right brachial artery 4 weeks after onset of the disease required upper-arm amputation. CONCLUSION: One of the decisive factors for the prognosis of TSLS is early antibiotic treatment. The prodromal symptoms in this case underline the necessity of early recognition and treatment to prevent a full-blown picture of the syndrome.

Corynebacterium lipophiloflavum sp. nov. isolated from a patient with bacterial vaginosis.

A unique coryneform bacterium was isolated from a patient with bacterial vaginosis. Chemotaxonomical investigations demonstrated that the unknown bacterium belonged to the genus Corynebacterium. The yellow-pigmented, slightly lipophilic, oxidative, urea-hydrolyzing bacterium could be phenotypically readily differentiated from the other members of the genus Corynebacterium. Comparative 16S rRNA gene analysis revealed that the bacterium represented a new subline within the genus Corynebacterium for which the name Corynebacterium lipophiloflavum sp. nov. is proposed. The type strain is CCUG 37336 (DSM 44291).

[Cat scratch disease. Bartonella henselae antibodies and DNA detection in regional lymphadenopathy]. / Katzenkratzkrankheit. Bartonella-henselae-Antikörper und Nukleinsäurenachweis bei regionaler Lymphadenopathie.

HISTORY AND CLINICAL FINDINGS: Two hard, pressure-sensitive nodules developed in the lower jaw of a 22-year-old woman. After a dental cause had been excluded, she was treated for suspected tonsillitis with Ceftibuten. Erythrocyte sedimentation rate was increased to 18 mm in the first hour. There were no other significant biochemical findings and fine-needle biopsy of one of the nodules showed nonspecific inflammatory reaction. INVESTIGATIONS: Sonography revealed two lymph nodes, 7 and 22 mm in diameter. Suspected cat scratch disease was confirmed by immunofluorescence with Bartonella (Rochalimaea) henselae and quintana antigens. TREATMENT AND COURSE: After a course of Clarithromycin (250 mg twice daily) for 6 weeks the lymph nodes had shrunk and the overlying skin was thin and discoloured brown. One node was incised and drained and the material examined. Microbiology was negative, but DNA sequencing confirmed Bartonella henselae. As a consequence, Rifampicin was given for 2 months (600 mg daily). Wound healing was very slow and the scar had regressed little after 9 months.

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.

[Gardnerella vaginalis: transport, microscopy, testing resistance]. / Gardnerella vaginalis: Transport, Mikroskopie, Resistenztestung.

UNLABELLED: G. vaginalis is an important pathogen in the aetiology of bacterial vaginosis. Therefore, we investigated the influence of transport systems in isolation, a scoring system for Gram stains, and susceptibility to antimicrobial agents. The comparison between a simple (Transwab) and a sophisticated (Port-A-Cul) system showed no differences with regard to for instance Enterococcus faecalis or Escherichia coli; however, isolation of G. vaginalis, a fastidious microorganism, was significantly higher (alpha < 0.0001) in Port-A-Cul. There was a strong correlation (97.5%) using the scoring system indicating bacterial vaginosis and isolation of G. vaginalis. The minimal inhibitory concentrations (MIC) of metronidazole for 60 strains of G. vaginalis were higher than 32 mg/l, some strains showing heteroresistance. This phenomenon may be an explanation for treatment failures. Clindamycin and erythromycin were much more active, with MIC's between 0.016 and 0.19 mg/l, in-vitro development of resistance being slower for clindamycin than for erythromycin. CONCLUSIONS: (I) for isolation of G. vaginalis, a sophisticated transport system is mandatory; (II) a scoring system for Gram staining is helpful in diagnosis of bacterial vaginosis; (III) in patients with metronidazole treatment failures, clindamycin should be used.

[Incidence and importance of Clostridium difficile in patients treated with antibacterial therapy or perioperative preventive cefoxitin administration]. / Häufigkeit und Bedeutung von Clostridium difficile bei Patientinnen mit antibakterieller Therapie oder perioperativer Cefoxitinprophylaxe.

Clostridium difficile and/or toxin B were isolated from the faeces of 3 (1.6%) of 184 patients within the first two days of hospitalisation in the University of Tübingen, Gynaecological Clinic. With following stool samples from a total of 117 patients the isolation rate of C. difficile was examined in relation to the treatment with antibiotics. From the first group of 61 patients, who had had gynaecological operations and were not treated with any antibiotic, the isolation rate of C. difficile rose statistically but not significantly from 0% at the time of admission up to 3.3% during hospitalisation. Amongst the second group of 17 patients, who had had gynaecological operations and were treated with various antibiotics for at least three days, the isolation rate was also found to rise insignificantly from 0 to 11.8% (p < 0.1). The third group of 33 patients, who had had gynaecological operations and perioperative prophylaxis with cefoxitin (one to three doses 2 g each), the isolation rate rose significantly from 0 to 12.1% (p < 0.05). The result of this study shows that the bacterial flora of the gut was probably altered even after a very brief application of cefoxitin. In two environmental examinations on the wards of the patients of this study, C. difficile was not isolated in any case.

Microbic superinfection in relapse of inflammatory bowel disease.

To assess the association between symptomatic relapse of inflammatory bowel disease (IBD) and superinfection with enteropathogenic microorganisms, we determined prospectively the incidence of infections with enteropathogenic bacteria, protozoa, and helminths in patients with confirmed longstanding IBD. Sixty-four patients with IBD (49 with Crohn's disease [CD] and 15 with ulcerative colitis [UC]) were consecutively enrolled in the study when relapse occurred. Multiple biopsies for histological and microbiological investigations were taken from all patients who were evaluated by colonoscopy. Parallel stool specimens were investigated for the presence of enteropathogenic bacteria, protozoa, and helminths. In six patients, we detected Clostridium difficile or toxin B (five CD, one UC), in one patient Campylobacter jejuni (CD), and in another patient Salmonella typhimurium (UC). Enteropathogenic Escherichia coli were isolated from three patients. Investigation of biopsies for Mycobacteria, microscopic examination of stool samples for helminths, and immunofluorescence for chlamydia were negative in all patients. In summary, as we found enteropathogenic microorganisms so infrequently in patients with relapse of IBD, despite intensive microbiological screening by tissue sampling for detection of gut adherent bacteria, we believe that microorganisms play only a minor role in the exacerbation of IBD.

Isolation of Ewingella americana from a patient with conjunctivitis.

Ewingella americana (family Enterobacteriaceae) was isolated separately from both eyes of a 30-year-old woman. Clinical signs and symptoms included adhesive eyelids, itching and edematous upper and lower lids. Therapy with amoxicillin-clavulanate resulted in the relief of symptoms. Ewingella americana can be isolated worldwide, but seems to be a rare pathogen.

[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)

Comparative in vitro activity of cefpodoxime against anaerobes other than Bacteroides fragilis.

To assess the in vitro activity of cefpodoxime against anaerobic respiratory tract and oropharyngeal pathogens 77 strains belonging to 18 gram-negative and 7 gram-positive species were studied by means of agar dilution tests. For comparison cefuroxime, amoxicillin, amoxicillin + clavulanic acid and clindamycin were also tested. Cefpodoxime was found to be active at concentrations of less than or equal to 0.125 mg/l against Prevotella oralis, Prevotella buccalis, Prevotella bivia, Porphyromonas asaccharolytica, Bacteroides corporis, Bacteroides gracilis, Fusobacterium necrophorum, Fusobacterium naviforme and Propionibacterium acnes. Prevotella oris, Prevotella buccae, Fusobacterium nucleatum, Peptostreptococcus asaccharolyticus, and Ruminococcus bromii were inhibited at concentrations of less than or equal to 1 mg/l and Prevotella denticola, Prevotella melaninogenica, Prevotella intermedia, Porphyromonas gingivalis, Bacteroides pneumosintes, and Peptostreptococcus micros at concentrations of less than or equal to 4 mg/l. Strains of Veillonella parvula were inhibited by cefpodoxime at 0.25-8 mg/l, and single strains of Peptostreptococcus anaerobius and Peptostreptococcus magnus showed MICs of 32 and 64 mg/l, respectively. The results obtained warrant the use of cefpodoxime in therapy of anaerobic and mixed aerobic-anaerobic infections of the upper and lower respiratory tract and similar infections not involving Bacteroides fragilis.

Effect of daptomycin, metronidazole and mezlocillin combinations on mixed bacterial cultures involving facultative and anaerobic bacteria.

The in vitro activities of different daptomycin concentrations in combination with metronidazole (4 mg/l) or/and mezlocillin (8 mg/l) were investigated on mixed bacterial cultures involving gram-positive facultative cocci. Bacteroides fragilis group strains and Escherichia coli. When Streptococcus faecalis alone or together with E. coli was cultured with B. thetaiotaomicron the colony counts of the latter were 4 log units higher after incubation in the presence of daptomycin and metronidazole than when it was cultured alone. After the addition of mezlocillin, this effect disappeared and all 3 strains were killed. When the same antibiotic combinations were used in the presence of beta-lactamase producing Staphylococcus aureus, the activity of mezlocillin was decreased significantly. The colony counts of the co-cultured B. thetaiotaomicron and E. coli proved to be 2 log and 6 log higher, respectively, than those observed after they were cultured alone. The antimicrobial susceptibilities of the clinical isolates tested here in mixed cultures of up to 3 strains were modified significantly by interactions between the strains and the antibiotics used.

Rapid methods and computer assisted diagnosis in medical microbiology.

Rapid diagnosis and reporting in medical microbiology is becoming more and more important. In recent years, introduction of automated instruments as well as of computer assisted diagnosis contributed to this aim. These methods, however, are very expensive. A more cost efficient and simple to perform method for rapid diagnosis is the use of specific fluorogenic substrates incorporated into culture media (solid or liquid) for identification of the most important pathogens, e.g. Escherichia coli. Investigation of Fluorocult ECD agar and Columbia agar revealed a high sensitivity (85%) and an excellent specificity (greater than 99%) of fluorescence in combination with a positive indole reaction for identification of E. coli.