Lars G. Burman

Increased Sporulation Rate of Epidemic Clostridium difficile Type 027/NAP1

ABSTRACT Clostridium difficile PCR ribotype 027 comprised 0.2% of a collection of Swedish isolates in 1997-2001 (3 of 1,325 isolates). These isolates had lower moxifloxacin MICs than the epidemic type 027 isolates, but they had the same tcdC sequence and toxin yield. Type 027 produced 3- to 13-fold more toxin than did major Swedish types. One epidemic strain (027/NAP1a) sporulated more than did other type 027 isolates, a feature that should contribute to its survival and spread.

Correlation of Disease Severity with Fecal Toxin Levels in Patients with Clostridium difficile-Associated Diarrhea and Distribution of PCR Ribotypes and Toxin Yields In Vitro of Corresponding Isolates

ABSTRACT We investigated in vivo and in vitro yields of toxins A and B from and PCR ribotypes of Clostridium difficile isolates from 164 patients with differing severities of C. difficile-associated diarrhea (CDAD) (patients were grouped as follows: <3 loose stools per day, n = 45; 3 to 10 per day, n = 97; >10 per day, n = 22). The median fecal toxin levels in each group were 0.5, 6.8, and 149 U/g feces (P < 0.001), respectively. Patients with severe diarrhea also had more-frequent occurrence of blood in stool and vomiting, but there was no association with fecal toxin levels per se. There was no correlation between fecal toxin level and toxin yield in vitro for the corresponding C. difficile isolate or between its PCR ribotype and disease severity. A broad range of toxin yields among isolates belonging to major PCR ribotypes indicated a presence of many subtypes. We hypothesize that bacterial and host factors that affect C. difficile toxin levels in feces are important determinants of symptoms in CDAD patients. An inverse correlation between toxin yield and spore count (r = 0.66) in stationary-phase cultures supported the notion that toxin production and sporulation represent opposite alternative survival strategies for C. difficile cells facing nutrient shortage.

Antimicrobial Susceptibility Pattern of Clostridium difficile and Its Relation to PCR Ribotypes in a Swedish University Hospital

ABSTRACT All 238 Clostridium difficile isolates were susceptible to metronidazole and vancomycin, whereas 84% and 1% were resistant to clindamycin and fusidic acid. Etest MICs for metronidazole were lower than agar dilution MICs (P < 0.01) but without difference in susceptible-intermediate-resistant categorization. No particular PCR ribotype was associated with clindamycin or fusidic acid resistance.

In vitro susceptibility to 17 antimicrobials of clinical Clostridium difficile isolates collected in 1993–2007 in Sweden

This study investigated the MICs of 17 antimicrobials, for 606 toxigenic clinical isolates of Clostridium difficile collected between 1993 and 2007 in Sweden. Low MIC(90) values were found for metronidazole (0.5 mg/L), vancomycin (1.0 mg/L), teicoplanin (0.125 mg/L), fusidic acid (1.0 mg/L), linezolid (2.0 mg/L), daptomycin (2.0 mg/L) and tigecycline (0.064 mg/L). Three isolates (0.5%) had elevated MICs for vancomycin (4-8 mg/L); however, these isolates originated from the same patient, who was receiving long-term intravenous vancomycin treatment. High-level clindamycin resistant isolates (MIC >256 mg/L) peaked in 1997 with 39 of 95 (41%) and out of these, 36% were also highly resistant to erythromycin. beta-Lactams such as penicillin V and piperacillin displayed MIC(90)s of 8 and 32 mg/L, respectively, whereas MICs of cefuroxime were >256 mg/L for all isolates. Universal resistance to ciprofloxacin and levofloxacin was found, and resistance to moxifloxacin increased from 4% of isolates in 2004 to 23% in 2007. Notably, these moxifloxacin-resistant isolates did not belong to the recent epidemic PCR ribotype 027, but to the pre-existing epidemic type 012 (82%), and these isolates accounted for the majority of isolates that were resistant to clindamycin (70%), tetracycline (84%) and rifampicin (92%) as well. This investigation of susceptibility data on clinical C. difficile isolates showed variations of multiresistance to be due to a specific PCR ribotype 012, emphasizing the importance of genotyping when evaluating emerging resistance over time.

High antibiotic susceptibility among bacterial pathogens in Swedish ICUs Report from a nation-wide surveillance program using TA90 as a novel index of susceptibility

Local infection control measures, antibiotic consumption and patient demographics from 1999–2000 together with bacteriological analyses were investigated in 29 ICUs participating in the ICU-STRAMA programme. The median antibiotic consumption per ICU was 1147 (range 605–2143) daily doses per 1000 occupied bed d (DDD1000). Antibiotics to which >90% of isolates of an organism were susceptible were defined as treatment alternatives (TA90). The mean number of TA90 was low (1–2 per organism) for Enterococcus faecium (vancomycin:VAN), coagulase negative staphylococci (VAN), Pseudomonas aeruginosa (ceftazidime:CTZ, netilmicin: NET) and Stenotrophomonas maltophilia (CTZ, trimethoprim-sulfamethoxazole: TSU), but higher (3–7) for Acinetobacter spp. (imipenem:IMI, NET, TSU), Enterococcus faecalis (ampicillin:AMP, IMI, VAN), Serratia spp. (ciprofloxacin:CIP, IMI, NET), Enterobacter spp. (CIP, IMI, NET, TSU), E. coli (cefuroxime:CXM, cefotaxime/ceftazidime:CTX/CTZ, CIP, IMI, NET, piperacillin-tazobactam:PTZ, TSU), Klebsiella spp. (CTX/CTZ CIP, IMI, NET, PTZ, TSU) and Staphylococcus aureus (clindamycin, fusidic acid, NET, oxacillin, rifampicin, VAN). Of S. aureus isolates 2% were MRSA. Facilities for alcohol hand disinfection at each bed were available in 96% of the ICUs. The numbers of TA90 available were apparently higher than in ICUs in southern Europe and the US, despite a relatively high antibiotic consumption. This may be due to a moderate ecological impact of the used agents and the infection control routines in Swedish ICUs.

Clinical and Bacteriological Effects of Therapy of Urinary Tract Infection in Primary Health Care: Relation to in vitro Sensitivity Testing

17 primary health care (PHC) centres participated in a 1-month evaluation of a county urinary tract infection (UTI) management program. A total of 302 patients contributing 355 episodes, dominated by female (93%), lower symptomatic (75%) and Escherichia coli (74%) episodes were studied. In therapeutic failure gram-negative bacteria other than E. coli showed an increased prevalence whereas Staphylococcus saprophyticus was not found. The general pattern of drug resistance was little influenced by UTI history and the mean pretherapy prevalence of resistance to the 7 antibacterial agents studied was low (7%). Drug resistance was increased in failure (mean 24%) also for agents not used for therapy (sulphonamides and nitrofurantoin) but not in early or repeated recurrence. UTI symptoms were eradicated in only two-thirds of bacteriologically cured episodes but in one-third of the failures at the posttreatment control. On average, therapy resulted in 8% bacteriological failure and 12% early recurrence. The bacteriological cure rate was the same irrespective of whether the infecting bacteria were classified as sensitive or resistant in vitro to the drug given. Thus, sensitivity testing of isolates is rarely needed in sporadic or recurrent UTI in PHC but may be relevant in failure. In order to be of prognostic value in uncomplicated UTI high-level breakpoints focusing more on peak urinary drug concentrations need to be studied.

Limited Value of Routine Microbiological Diagnostics in Patients Hospitalized for Community-acquired Pneumonia

Current guidelines recommend microbiological diagnostic procedures as a part of the management of patients hospitalized for community-acquired pneumonia (CAP), but the value of such efforts has been questioned. Patients hospitalized for CAP were studied retrospectively, focusing on the use of aetiological diagnostic methods and their clinical impact. Adult patients, without known human immunodeficiency virus infection, admitted to hospital for CAP during 12 months, were evaluated with regard to the importance of aetiological diagnosis for tailoring antibiotic therapy, antibiotic-associated diarrhoea, Clostridium difficile disease, length of hospital stay and mortality. Of the 605 studied patients, 482 (80%) were subjected to Mycoplasma pneumoniae and/or respiratory virus serology and/or cultures of blood and/or sputum. They had a better prognosis than patients not subjected to microbiological diagnostics (mortality within 3 months was 9% vs 24%, p = 0.001), apparently reflecting differences in general health (e.g. less dementia diagnosis) but not the outcome of diagnostics. A presumptive aetiology was obtained only in 132 of the 482 patients, Streptococcus pneumoniae and M. pneumoniae being the most common agents (in 49 and 36 patients, respectively). Establishing an aetiological diagnosis had no impact on the number of in-hospital changes of therapy, on the proportion of new regimens having a narrower antimicrobial spectrum than the initial one or on the outcome. Therapy was changed to a drug directed specifically against the identified pathogen in only 16 out of these 132 patients and again without any overall improvement in the outcome variables. In a setting with a low frequency of antibiotic-resistant respiratory tract pathogens current routine microbiological diagnostics were found to be of limited value for the clinical management of patients hospitalized for CAP. Improved diagnostics in CAP are urgently needed, as establishing an aetiological diagnosis carries a potential for optimizing the antibiotic therapy.

Antibiotic prescription practices, consumption and bacterial resistance in a cross section of Swedish intensive care units

Background: The purpose of this work was to study usage of antibiotics, its possible determinants, and patterns of bacterial resistance in Swedish intensive care units (ICUs).

Urinary Tract Infection in Primary Health Care in Northern Sweden: I. Epidemiology

During a 12-month study at the primary health care (PHC) centre in Vännäs (population 8,000) 632 encounters by 265 individuals because of suspected urinary tract infection (UTI) or control after treatment resulted in 279 episodes of bacteriuria in 185 patients. Nine per cent of the episodes concerned patients with indwelling catheter or incontinence requiring other aids. Symptoms of lower and higher UTI were recorded in 56 and 12%, respectively, whereas one third of the episodes were associated with vague or no symptoms and discovered mainly at planned treatment controls. The annual incidence of bacteriuria recorded increased from 0.5% in the first decade of life to more than 10% in the age group 90-100 years. Male UTI comprised 13% of the episodes, increased after middle age and contributed 40% at greater than or equal to 80 years of age. The risk of recurrence (on average 50% during the year studied) was relatively independent of sex and age. No seasonal variation of UTI was observed except for a peak in late summer due to Staphylococcus saprophyticus confined to females aged 15-64 years and causing 28% of the episodes in August. Although UTI in PHC appears to be similar globally it represents a far more complex patient group than indicated by the UTI drug trials frequently published.

Control of an outbreak of a highly beta-lactam-resistant Enterobacter cloacae strain in a neonatal special care unit.

Two successive outbreaks of colonization and infection with Enterobacter cloacae resistant to third generation cephalosporins (cephalosporin‐resistant E. cloacae, CREC) and involving 15 infants occurred within 12 months in a neonatal special care unit. Isolates of clinical significance were obtained from four infants (urine 2 cases, blood, pleural drainage). According to epidemiological typing using computerized biochemical fingerprinting and pulsed‐field gel electrophoresis (PFGE) the same CREC strain was found in both outbreaks. The origin of the strain and its reservoir between the two outbreaks remained unknown. Emphasizing strict barrier nursing of the infants had little or no impact on the presence and transmission of the strain in the unit. In contrast, replacing ampicillin plus cefotaxime as standard empiric therapy with penicillin G plus netilmicin plus consequent cohorting of newborns and staff promptly halted both the outbreaks. During a 5‐y follow‐up after the last episode, the choice of antibiotics for empirical treatment has varied, and no further outbreaks of CREC have been seen, with the exception of two sporadic cases.