Anna-Stina Malmborg

BACTERIAL COLONISATION WITH XANTHOMONAS MALTOPHILIA : A RETROSPECTIVE STUDY IN A CYSTIC FIBROSIS PATIENT POPULATION

SummaryXanthomonas maltophilia was isolated from 25 of 150 patients with cystic fibrosis during a period of 10 years (1983–1992). Twelve patients harbouredX. maltophilia chronically, i.e. repeatedly for more than 6 months. No predisposing factors for the colonisation could be identified by studying the clinical and laboratory data of the patients, including preceding and concurrent bacterial colonisation with other bacteria, antibacterial treatments, pulmonary function and biochemical markers. Up to 2 years after the chronic colonisation was established no clinical deterioration could be verified, but the patients withX. maltophilia generally had a worse lung function at the latest follow-up (2–7 years after colonisation) than controls colonised withPseudomonas aeruginosa (p<0.05). Our data imply thatX. maltophilia is a pathogen and the colonisation appears to follow the same pattern as the colonisation byP. aeruginosa. The development of resistance to different antibiotics, as revealed by analysis of the inhibition zones, was related to antibacterial treatment courses.X. maltophilia showed reduced sensitivity to the most commonly used antibiotics, ceftazidime and tobramycin.ZusammenfassungXanthomonas maltophilia wurde bei 25 von 150 Patienten während eines Zeitraumes von 10 Jahren (1983–1992) isoliert. 12 Patienten hatten eine chronische Kolonisierung, das heißt bestehend während mehr als 6 Monaten. Prädisponierende Faktoren konnten bei der Analyse der klinischen Daten und Labordaten nicht festgestellt werden, frühere und gleichzeitige Kolonisierung mit anderen Bakterien, Lungenfunktion und biochemische Parameter inbegriffen. Bis zu 2 Jahre nachdem die chronische Kolonisierung etabliert worden war, fanden wir keine klinische Verschlechterung. Die langfristige Verlaufskontrolle (2–7 Jahre) zeigte, daß Patienten mitX. maltophilia meistens eine schlechtere Lungenfunktion hatten als Kontrollfälle, die mitPseudomonas aeruginosa kolonisiert worden waren (p<0,05). Unsere Daten deuten an, daß bei Patienten mit zystischer FibroseX. maltophilia ein pathogener Erreger ist und die Kolonisierung nach demselben Muster zu erfolgen scheint wie die Kolonisierung mitP. aeruginosa. Die Entwicklung der Antibiotikaresistenz wurde durch Bestimmung der Hemmzonen im Verhältnis zu Antibiotikabehandlungen verfolgt.X. maltophilia zeigte eine herabgesetzte Empfindlichkeit gegen die meisten Antibiotika. In unserer Serie gab es eine markante Resistenzentwicklung gegen Ceftazidim und Tobramycin während der chronischen Kolonisierung.Xanthomonas maltophilia was isolated from 25 of 150 patients with cystic fibrosis during a period of 10 years (1983–1992). Twelve patients harbouredX. maltophilia chronically, i.e. repeatedly for more than 6 months. No predisposing factors for the colonisation could be identified by studying the clinical and laboratory data of the patients, including preceding and concurrent bacterial colonisation with other bacteria, antibacterial treatments, pulmonary function and biochemical markers. Up to 2 years after the chronic colonisation was established no clinical deterioration could be verified, but the patients withX. maltophilia generally had a worse lung function at the latest follow-up (2–7 years after colonisation) than controls colonised withPseudomonas aeruginosa (p<0.05). Our data imply thatX. maltophilia is a pathogen and the colonisation appears to follow the same pattern as the colonisation byP. aeruginosa. The development of resistance to different antibiotics, as revealed by analysis of the inhibition zones, was related to antibacterial treatment courses.X. maltophilia showed reduced sensitivity to the most commonly used antibiotics, ceftazidime and tobramycin. Xanthomonas maltophilia wurde bei 25 von 150 Patienten während eines Zeitraumes von 10 Jahren (1983–1992) isoliert. 12 Patienten hatten eine chronische Kolonisierung, das heißt bestehend während mehr als 6 Monaten. Prädisponierende Faktoren konnten bei der Analyse der klinischen Daten und Labordaten nicht festgestellt werden, frühere und gleichzeitige Kolonisierung mit anderen Bakterien, Lungenfunktion und biochemische Parameter inbegriffen. Bis zu 2 Jahre nachdem die chronische Kolonisierung etabliert worden war, fanden wir keine klinische Verschlechterung. Die langfristige Verlaufskontrolle (2–7 Jahre) zeigte, daß Patienten mitX. maltophilia meistens eine schlechtere Lungenfunktion hatten als Kontrollfälle, die mitPseudomonas aeruginosa kolonisiert worden waren (p<0,05). Unsere Daten deuten an, daß bei Patienten mit zystischer FibroseX. maltophilia ein pathogener Erreger ist und die Kolonisierung nach demselben Muster zu erfolgen scheint wie die Kolonisierung mitP. aeruginosa. Die Entwicklung der Antibiotikaresistenz wurde durch Bestimmung der Hemmzonen im Verhältnis zu Antibiotikabehandlungen verfolgt.X. maltophilia zeigte eine herabgesetzte Empfindlichkeit gegen die meisten Antibiotika. In unserer Serie gab es eine markante Resistenzentwicklung gegen Ceftazidim und Tobramycin während der chronischen Kolonisierung.

Granulocyte elastase-α1-antiproteinase complex in cystic fibrosis: Sensitive plasma assay for monitoring pulmonary infections

Elastase in plasma was determined as a complex of granulocyte elastase and alpha 1-antiproteinase (GEC) by an enzyme-linked immunosorbent assay in 67 patients with cystic fibrosis. The patients were observed for 1 years, when clinically infected and noninfected. Although noninfected patients had GEC levels within the normal range, the mean value was significantly higher than the mean values in patients in an optimal noninfectious state (P less than 0.01) and in healthy controls (P less than 0.001). Clinical signs of (in most cases) low-grade infection were paralleled by significant increases in GEC levels (P less than 0.001). There was no correlation with different types of bacteria or age of patients. No cross reaction to Pseudomonas elastase could be found in vitro or in vivo. Significant decreases of GEC values were seen after intravenously administered antimicrobial therapy (P less than 0.001), and although the white blood cell count and erythrocyte sedimentation rate were rarely increased above the normal range, they decreased congruently (P less than 0.001), and lung function improved (P less than 0.001). The sensitivity of GEC was significantly higher than that for erythrocyte sedimentation rate (P less than 0.01) and white blood cell count (P less than 0.05). Determination of GEC values seems to be a simple and sensitive measurement for monitoring treatment in cystic fibrosis, especially of low-grade infections in patients with normal standard blood tests.

The effect of piperacillin prophylaxis on the colonic microflora in patients undergoing colorectal surgery

SummaryPiperacillin was given parenterally in doses of 4 g every 8 h for two days to 20 patients undergoing colorectal surgery. A series of serum and fecal specimens were taken to analyse piperacillin concentrations. Tissue samples from the gut wall were taken during surgery. The maximum serum concentrations during surgery were reached 15 min after piperacillin administration. On Day 0 the mean half-life was 1.9 h and the mean area under the serum concentration curve was 536.8 mg/l. The piperacillin concentrations in the tissue samples ranged from 4.2 to 103.5 mg/kg. The tissue/serum ratio was 0.45. The piperacillin concentrations in the fecal samples ranged from not detectable to 101.2 mg/kg. Fecal samples were also collected during the investigation period for the cultivation of aerobic and anaerobic bacteria. Of the aerobic bacteria, enterococci, streptococci and enterobacteria decreased in one fourth of the patients during the prophylaxis period. Anaerobic bacteria, e. g. cocci, gram-positive rods, fusobacteria and bacteroides, decreased in two thirds of the patients during the same period. After the piperacillin administration period, the aerobic and anaerobic colon microflora returned to the pre-treatment pattern in most patients. Postoperative infections due toEscherichia coli, Morganella morganii, Bacteroides fragilis, peptococci and peptostreptococci occurred in two patients.Zusammenfassung20 Patienten, die sich einer kolorektalen Operation unterziehen mußten, wurde Piperacillin parenteral in Dosen von 4 g achtstündlich zwei Tage lang verabreicht. Zur Bestimmung der Piperacillin-Konzentrationen wurden eine Reihe von Serum- und Stuhlproben gewonnen. Während der Operation wurden Gewebeproben von der Darmwand entnommen. Intraoperativ wurden 15 min nach Piperacillin-Applikation maximale Serumkonzentrationen erreicht. Am Tag 0 betrug die mittlere Halbwertszeit 1,9 h und die Fläche unter der Serumkonzentrationszeitkurve im Mittel 536,8 mg/l. In den Gewebeproben lagen die Piperacillin-Konzentrationen zwischen 4,2 und 103,5 mg/kg. Die Relation der Konzentrationen im Gewebe/Serum betrug 0,45. Die Piperacillin-Konzentrationen in den Stuhlproben reichten von nicht nachweisbar bis 101,2 mg/kg. Für die Kultivierung aerober und anaerober Bakterien wurden ebenfalls Stuhlproben gewonnen. Während der Dauer der Piperacillin-Prophylaxe nahmen von den aeroben Bakterien Enterokokken, Streptokokken und Enterobakterien bei einem Viertel der Patienten ab; von den anaeroben Bakterien reduzierten sich z. B. Kokken, grampositive Stäbchen, Fusobakterien und Bacteroides bei zwei Drittel der Patienten. Nach der Applikations-phase von Piperacillin stellte sich bei den meisten Patienten wieder dasselbe Verteilungsmuster aerober und anaerober Kolonflora ein wie vorher. Bei zwei Patienten traten postoperative Infektionen durchEscherichia coli, Morganella morganii, Bacteroides fragilis, Peptokokken und Peptostreptokokken auf.

Effect of aztreonam on the colon microflora in patients undergoing colorectal surgery

SummaryAztreonam was given intravenously at a dose of 1 g at induction of anaesthesia, followed by subsequent doses of 1 g at eight hour intervals during 48 hours to 20 patients undergoing colorectal surgery. A series of serum and faecal specimens were taken for analysis of aztreonam concentrations. Tissue samples from the gut wall were taken at surgery. The maximum serum concentrations (mean value 114.7 mg/l) during surgery were reached 15 minutes after aztreonam administration. The aztreonam concentration in the tissue samples varied from 4.1–28.3 mg/kg and the concentration in the faecal samples from 0.4–34.4 mg/kg. Faecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. Enterobacteria were suppressed significantly during the prophylaxis period and there was a significant increase of staphylococci in ten of the patients. Three of these patients developed postoperative wound infections with staphylococci. Among the anaerobic bacteria, only minor changes were observed during the same period. After two weeks, the microflora was normalized in all patients. Five postoperative infections including an anastomose dehiscence in one patient occurred.ZusammenfassungAztreonam wurde bei Einleitung der Anästhesie in einer Dosis von 1 g an 20 Patienten, bei denen colorektale Operationen durchgeführt wurden, intravenös appliziert; im Abstand von acht Studen wurden 48 Stunden lang jeweils weitere 1 g-Dosen verabreicht. Zur Bestimmung der Aztreonam-Konzentrationen wurde eine Reihe von Serum- und Stuhlproben gewonnen. Unter der Operation wurden Gewebeproben vom Darm entnommen. 15 Minuten nach Aztreonam-Gabe wurden unter der Operation die höchsten Aztreonam-Serumkonzentrationen erreicht (Mittelwert 114,7 mg/l). In den Gewebeproben fanden sich Aztreonam-Konzentrationen von 4,1–28,3 mg/kg, in den Stuhlproben von 0,4–34,4 mg/kg. Zur Anzüchtung aerober und anaerober Bakterien wurden im Untersuchungszeitraum ebenfalls Stuhlproben gewonnen. Während der Prophylaxephase war eine erhebliche Suppression der Enterobakterien festzustellen, gleichzeitig stiegen bei zehn Patienten die Staphylokokken signifikant an. Bei drei dieser Patienten traten postoperative Wundinfektionen mit Staphylokokken auf. Die anaerobe Bakterienpopulation änderte sich im selben Zeitraum nur geringfügig. Nach zwei Wochen hatte sich bei allen Patienten die Mikroflora normalisiert. Insgesamt traten fünf postoperative Infektionen auf, einschließlich einer Anastomosendehiszenz bei einem Patienten.

Impact of Different Betalactam Antibiotics on the Normal Human Flora, and Colonization of the Oral Cavity, Throat and Colon

SummaryPhenoxymethylpenicillin was given orally in doses of 800 mg twice daily for seven days to six patients, and bacampicillin was given in doses of 400 mg three times per day for seven days to another six patients. Saliva, throat and faecal specimens were taken for cultivation of aerobic and anaerobic bacteria. Only small changes in the normal saliva and throat flora were observed, and no changes in the faecal flora were noticed during the observation period. Cefoxitin was administered parenterally in doses of 2 g at 6 h intervals for 12 h to six other patients. Pronounced changes in the colon flora occurred. Of the aerobic bacteria, enterobacteria decreased and cefoxitin-resistant enterococci increased in number; of the anaerobic bacteria, gramnegative rods decreased in number. At the end of the administration period, all cefoxitin-resistant strains decreased, and suppressed enterobacteria and bacteroides increased in number.ZusammenfassungSechs Personen erhielten sieben Tage lang Phenoxymethylpenicillin oral in Dosen von 800 mg zweimal täglich. Sechs weitere Personen erhielten sieben Tage lang Bacampicillin in Tablettenform in Dosen von 400 mg dreimal täglich. Zur Kultivierung aerober und anaerober Bakterien wurden Speichel, Rachenabstriche und Stuhlproben entnommen. Im Beobachtungszeitraum waren nur geringe Veränderungen der normalen Speichel- und Rachenflora und keine Veränderungen der faekalen Flora zu beobachten. Sechs Patienten erhielten über einen Zeitraum von zwölf Stunden 2 g Cefoxitin in sechsstündlichen Abständen parenteral appliziert. Daraufhin traten ausgeprägte Veränderungen in der Zusammensetzung der Colonflora auf. Unter den aeroben Bakterien nahmen die Enterobakterien ab, cefoxitinresistente Enterokokken nahmen zu; unter den anaeroben Bakterien war die Zahl der gramnegativen Stäbchen reduziert. In der Phase nach der Antibiotikaapplikation nahm die Zahl aller cefoxitinresistenten Stämme ab, und die supprimierten Enterobakterien und Bacteroidesstämme vermehrten sich wieder.Phenoxymethylpenicillin was given orally in doses of 800 mg twice daily for seven days to six patients, and bacampicillin was given in doses of 400 mg three times per day for seven days to another six patients. Saliva, throat and faecal specimens were taken for cultivation of aerobic and anaerobic bacteria. Only small changes in the normal saliva and throat flora were observed, and no changes in the faecal flora were noticed during the observation period. Cefoxitin was administered parenterally in doses of 2 g at 6 h intervals for 12 h to six other patients. Pronounced changes in the colon flora occurred. Of the aerobic bacteria, enterobacteria decreased and cefoxitin-resistant enterococci increased in number; of the anaerobic bacteria, gramnegative rods decreased in number. At the end of the administration period, all cefoxitin-resistant strains decreased, and suppressed enterobacteria and bacteroides increased in number. Sechs Personen erhielten sieben Tage lang Phenoxymethylpenicillin oral in Dosen von 800 mg zweimal täglich. Sechs weitere Personen erhielten sieben Tage lang Bacampicillin in Tablettenform in Dosen von 400 mg dreimal täglich. Zur Kultivierung aerober und anaerober Bakterien wurden Speichel, Rachenabstriche und Stuhlproben entnommen. Im Beobachtungszeitraum waren nur geringe Veränderungen der normalen Speichel- und Rachenflora und keine Veränderungen der faekalen Flora zu beobachten. Sechs Patienten erhielten über einen Zeitraum von zwölf Stunden 2 g Cefoxitin in sechsstündlichen Abständen parenteral appliziert. Daraufhin traten ausgeprägte Veränderungen in der Zusammensetzung der Colonflora auf. Unter den aeroben Bakterien nahmen die Enterobakterien ab, cefoxitinresistente Enterokokken nahmen zu; unter den anaeroben Bakterien war die Zahl der gramnegativen Stäbchen reduziert. In der Phase nach der Antibiotikaapplikation nahm die Zahl aller cefoxitinresistenten Stämme ab, und die supprimierten Enterobakterien und Bacteroidesstämme vermehrten sich wieder.

Septic complications in relation to factors influencing the gastric microflora in patients undergoing gastric surgery.

Postoperative septic complications and micro-organisms found in primary infections were studied in 750 gastric operations performed between 1972 and 1986. The overall rate of primary infections was 23%. The infection rates were related to the diagnosis and to factors that could influence the colonization of the stomach. No significant differences in the rates of postoperative infections were found between patients who had received preoperative antibiotic prophylaxis and those who had not. In all groups of patients, aerobic and anaerobic gram-positive and gram-negative bacteria and yeasts were isolated in primary infections. Enterobacteriaceae, enterococci and Bacteroides fragiis were more frequent in patients with gastric bleeding or carcinoma.

Penetration of imipenem into human pancreatic juice following single intravenous dose administration.

The penetration of imipenem into the human pancreatic juice following a single intravenous dose of 500 mg was investigated in five patients who had undergone pancreatic transplantation. With a special technique for segmental pancreatic transplantation it was possible to collect pure pancreatic juice at regular intervals. Simultaneous blood and pancreatic juice samples were collected immediately before drug administration and then at 0.5, 1, 1.5, 2.5, 3.5 and 5.5 h thereafter. The antibiotic concentrations were determined by the agar diffusion method. The mean peak level in serum was 24.6 +/- (SE) 2.6 mg/l and occurred 0.5 h after administration. The mean peak concentration in pancreatic juice was not reached until 1.5 h after administration, and the level was then 1.7 +/- (SE) 0.3 mg/l. Thereafter the levels in serum and pancreatic juice declined in parallel, and the concentration in pancreatic juice was then about 13% of that in serum. Although imipenem penetrates into the pancreatic juice at a very low degree, the concentrations exceeded the MIC values for many bacteria associated with pancreatic infections. Imipenem could therefore be an alternative as monotherapy in the treatment of pancreatic infections.

Cystic Fibrosis Pulmonary Infection: The Swedish Experience

Since the late 1960s, centres for cystic fibrosis (CF) patients have slowly been able to grow and now care for most of the patients with the disease in Sweden. At present there are close to 400 patients with CF out of a population of about 8 million inhabitants. About 340 of these are known to the three centres at the university clinics in Lund, Goteborg and Stockholm. Local screening programmes and genetic studies have indicated that the incidence in Sweden, as well as in the other Nordic countries, is lower than in central Europe and North America, approaching 1:4000 live births [1, 2].

Effects of antimicrobial prophylaxis on colonization resistance

The effect of antimicrobial agents on the intestinal microflora of patients undergoing colorectal surgery was examined. Two narrow spectrum agents, clindamycin and aztreonam, disturbed colonization resistance. This was preserved with the broad spectrum compound, imipenem. Ecological effects are difficult to predict and clinical studies of new antibiotics should include investigations of their impact on the normal human intestinal flora.

Hospital and catchment area antibiotic utilization and bacterial sensitivity in primary infections following gastric surgery in Huddinge, Sweden

SummaryThe relationship between hopsital and catchment area ultilization of antimicrobial agents and the antibiotic sensitivity of bacteria isolated from primary infections has been studied after 750 gastric operations performed between 1972 and 1986 at the Huddinge University Hospital.Over 80% of the antibiotics were used in the catchment area. Penicillins (G and V) overall were the most commonly used drugs and comprised 37% of the total antibiotic consumption in 1977–1986.Narrow-spectrum antibiotics dominated throughout the period under investigation. No change in the bacterial resistance to antimicrobial agents was found over time.Many strains of Klebsiella/Enterobacter and E. coli resistant to ampicillin and tetracyclines were recovered throughout the period under investigation. No aerobic Gram-negative bacteria were resistant to gentamicin. All Bacteroides strains except two were sensitive to cefoxitin. Tetracyclines and ampicillin/amoxycillin were mainly used in the catchment area, and cefoxitin and aminoglycosides were almost exclusively used in the hospital.Antimicrobial agents primarily used for out-patients in the catchment area seemed to have more influence on the susceptibility of microorganisms isolated from postoperative infections than agents primarily used in the hospital.