Summaries from the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy: Part I

CONFERENCE COVERAGE

Note: The following summaries represent a selection of papers from those presented at the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) held September 24-27, 1998, in San Diego, CA. It is important to recognize that many of these summaries are extracted only from the published abstracts, and it is possible that some of the material presented at the conference may have differed. -Stan Deresinski, MD, FACP

General Infectious Diseases

Respiratory Tract Infections

Twelve Swedish patients 23-75 years of age with nasal congestion for at least one year underwent investigation to evaluate the potential role of infection with Chlamydia pneumoniae in their chronic rhinitis. C. pneumoniae was detected in throat specimens by PCR in 10 of the 12, nine had specific serum antibodies to C. pneumoniae, and 10 had positive immunohistochemical staining for C. pneumoniae on mucosal biopsy (4 of 7 nose biopsies, and 10 of 11 throat biopsies were positive). All 11 became asymptomatic after macrolide treatment, but most relapsed 2-12 months later. (Abstract L-999.) This study suggests that C. pneumoniae may be a cause of chronic persistent rhinitis.

The clinician's dream of a "screening panel," for detection of respiratory pathogens in sputum, analogous to that used for serum chemistries, is coming closer to reality. An in-house multiplex RT-PCR was applied to sputum specimens, followed by reverse hybridization to detect nucleic acids of nine respiratory pathogens (influenza A and B, parainfluenzae types 1 and 3, RSV, enterovirus, adenovirus, M. pneumoniae, and C. pneumoniae). A study of 1017 consecutive children with respiratory tract infection using this technique uncovered a pathogen in 366 (36%), including 133 RSV, 69 influenza A, 49 adenovirus, 38 enterovirus, and 31 M. pneumoniae. (Abstract L-105.)

Sputum induction in order to obtain a useful specimen for the microbiologic diagnosis of pneumonia is commonly considered. However, sputum induction using hypertonic saline did not improve specimen quality, as determined by the ratio of PMNs to squamous epithelial cells on Gram stain, when compared to uninduced sputum. (Abstract D-1.)

A study of the Chiron acellular pertussis vaccine in adults demonstrated that it was immunogenic and well-tolerated, although discomfort at the injection site was reported by 45% of vaccine and only 14% of placebo recipients. (Abstract G-29.) It is undoubtedly only a matter of time before booster dosing with the acellular pertussis vaccine will be recommended for adults, particularly healthcare workers.

Eradication of Bordetella pertussis from the respiratory secretions of adults is often difficult, but perhaps the use of fluoroquinolones will help. The MIC90s of grepafloxacin, moxifloxacin, and ciprofloxacin against B. pertussis and B. parapertussis were each 0.03-0.06 mcg/mL. The MIC90 of clarithromycin against B. pertussis is also 0.06 mcg/mL, but against B. parapertussis, it is 2.09 mcg/mL. (Abstract E-212b.)

Meningitis

When can antibiotics be safely discontinued in the child with suspected meningitis whose CSF culture remains negative? Of 99 cases of culture proven bacterial meningitis in children, the CSF culture became positive within two calendar days in 96 (97%). (Abstract D-8.)

While resistance remains rare in the United States, the meningococcus is undergoing "MIC creep" in parts of Europe. Reduced susceptibility to penicillin (MIC 0.1-1.0 mcg/mL) was detected in 13 (22%) of 59 meningococcal isolates recovered from patients with meningitis in France. (Abstract L-30.)

Bactericidal antibacterial activity is believed to be necessary for cure of bacterial meningitis. Tolerance describes a circumstance in which an antibiotic inhibits a microorganism but may fail to kill it at achievable concentrations. Screening of 120 isolates of pneumococcus found that three (2.5%), all of serotype 9V, were tolerant to vancomycin, defined as log killing less than 2 ± 0.2 in four hours. (Saturday, Abstract LB-6.)

Quinupristin/dalfopristin was administered, along with systemic therapy, intrathecally into the lumbar space in a dose of 1 or 2 mg daily for 5-33 days in four patients with ventriculoperitoneal shunts infected with VRE, with improvement and without apparent toxicity. (Abstract E-167.)

Diabetic Foot Infections

Diabetes mellitus is associated with impaired PMN function. G-CSF, as well as GM-CSF, enhance the phagocytic activity and microbicidal capacity of PMNs. Thirty-six patients with limb-threatening diabetic foot infections, 33 of whom had osteomyelitis, were randomized to receive, in addition to conventional treatment, G-CSF for 21 days. No difference in cure rate or need for amputation was observed between the two treatment groups. (Abstract MN-31.) The small sample size, however, severely limits the power of this study.

Urinary Tract Infections

Resistance of urinary tract pathogens in the community to commonly used antibiotics continues to escalate. A study in Toronto of 5100 community-acquired urinary tract isolates found that 30% were resistant to trimethoprim or trimethoprim-sulfamethoxazole; 20% of E. coli were resistant. (Abstract E-34.) A University of Washington study found that the prevalence of such resistance among E. coli isolates from women with acute uncomplicated cystitis rose from more than 9% in 1992 to more than 18% in 1996. (Abstract E-40.) Most urinary tract E. coli isolates in the United States remain susceptible to fluoroquinolones and to fosfomycin. (Abstract E-51.)

One hundred eighteen women with acute pyelonephritis were randomized to receive a single IV dose of tobramycin (2 mg/kg) or placebo in addition to ciprofloxacin 500 mg bid. There was no benefit associated with the addition of the single dose of tobramycin. (Abstract L-88.)

Three hundred seventy-eight women with acute uncomplicated pyelonephritis were randomized to receive either po ciprofloxacin + initial IV ciprofloxacin for seven days or po trimethoprim-sulfamethoxazole (TS) + initial IV ceftriaxone for 14 days. Eighteen percent of isolates were resistant to TS, 0.5% to ceftriaxone, and none to ciprofloxacin. Bacteriologic eradication rates 4-11 days after the end of therapy were 99.1% in those assigned ciprofloxacin and 89% in those assigned TS-a statistically significant difference. A higher cure rate was associated with an initial IV dose in those given ceftriaxone and TS, but not in those treated with ciprofloxacin. The cost per patient was $336 for ciprofloxacin and $489 for TS. Drug-related adverse events occurred in 33% of TS recipients and 24% of those assigned TS. (Abstract L-83.)

These studies, taken together, strongly indicate that TS is inferior to ciprofloxacin in the treatment of urinary tract infection. Furthermore, they indicate that ciprofloxacin therapy may, in most cases, be administered orally from the outset.

Sixty-four elderly patients with permanent indwelling urinary catheters who had symptomatic UTI were randomized, at the time of institution of antibiotic therapy, to either replacement or non-replacement of the catheter. Replacement of the catheter was associated with a reduction in duration of fever from 5.7 to 2.8 days (P < 0.01), as well as more favorable rates of bacteriological cure 72 hours after the start of therapy and at seven and 28 days after completion. (Abstract K-105.)

Intraabdominal Infections

Surgical prophylaxis. One hundred sixty-one patients undergoing colorectal surgery were randomized to receive one of two prophylactic antibiotic regimens: single doses of gentamicin (4.5 mg/kg) and metronidazole (500 mg), or gentamicin 1.5 mg/kg q8h and metronidazole 500 mg-each given immediately pre-operatively and every eight hours postoperatively for 24 hours. There was no overall efficacy difference between the two treatment arms. However, the single-dose regime was more effective in those whose procedures were prolonged, possibly because of the high gentamicin concentration. (Abstract MN-47.)

Treatment. Two hundred twenty-seven evaluable patients with severe generalized peritonitis were randomized to receive either piperacillin/tazobactam alone or together with amikacin. There was no difference in outcome between the treatment arms. (Abstract MN-48.)

Four hundred forty-eight patients with complicated intraabdominal infection were randomized to receive, in a double-blind manner, either IV ciprofloxacin + IV metronidazole or IV piperacillin/tazobactam. After 48 hours, therapy could be switched to po; this was done in approximately 60% of each group, with po ciprofloxacin + po metronidazole most commonly prescribed. The clinical response rate was 74% in those assigned ciprofloxacin + metronidazole and only 63% in the piperacillin/tazobactam group (95%; CI = 0.03, 0.29). The incidences of post-surgical wound infections in the two groups were, respectively, 11% and 14% (P = 0.04). (Abstract MN-50.)

Sepsis

The serum concentration of procalcitonin, a calcitonin propeptide largely produced by extra-thyroidal tissues, has been reported to be a marker of severe infection. Reports suggest that it may be useful in the differentiation of bacterial from viral meningitis, as a marker for the presence of spontaneous bacterial peritonitis, and as a marker for the presence of bacteremia in patients with severe sepsis or septic shock. (Abstracts D-108-D-111.) Daily monitoring of serum procalcitonin in a medical ICU has been reported to provide early detection of sepsis. (Abstract D-112.) The true value of this test, however, remains to be determined.

Nosocomial Infections and Hospital Epidemiology

Flushing catheters with heparin is commonly performed in order to maintain patency. There may also be benefit to flushing with antimicrobial solutions as well. Central venous catheters in immunocompromised pediatric patients were flushed with either heparin, vancomycin + heparin, or vancomycin + heparin + ciprofloxacin, assigned randomly. Both catheter occlusion rates and catheter related infections were significantly lower in the cohorts assigned antibiotic containing solutions compared to those given heparin alone. No adverse effects occurred, and neither antibiotic could be detected in the bloodstream after flushing. (Abstract K-138a.)

It is increasingly apparent that a variety of devices commonly used in the hospital have the potential to serve as a reservoir of potentially pathogenic microorganisms. The surface of the base and probe handle of 24 hospital electronic ear-probe thermometers were all colonized with CNS. Among the other organisms recovered were MRSA, Enterococcus faecalis, and Viridans streptococci. (Abstract K-135.) Whether this represents a risk to patients, however, remains unclear.

Two methods that have been used in an attempt to control antibiotic resistance are antibiotic substitution and alternation of antibiotics. In one report, the introduction of cefepime in place of aztreonam or ceftazidime in an ICU and a hematology unit was associated with a reduced prevalence of resistance to the latter two agents. (Abstract K-14.)

In what must have been a surprising result, the institution of monthly "antibiotic alternans" of ticarcillin-clavulanate and ciprofloxacin + metronidazole in a 24-bed ICU was associated with a significant increase in antibacterial resistance of gram negative bacillary isolates. This resistance persisted after "antibiotic alternans" were discontinued. (Abstract K-13.)

Transplantation and Chemotherapy

The value of antifungal prophylaxis during chemotherapy-induced neutropenia in patients with hematologic malignancies remains a matter of dispute. Five hundred patients with hematologic malignancy and an expected duration of neutropenia of longer than 14 days were randomized to receive either itraconazole oral solution (5 mg/kg/d) or amphotericin B capsules (2 g/d) as antifungal prophylaxis. The number of superficial infections was reduced in those receiving itraconazole (2 vs 13; P < 0.01). While there was a trend toward fewer proven deep fungal infections (8 vs 13), proven aspergillosis (5 vs 9), and deaths with deep fungal infection (1 vs 5), none of these differences achieved statistical significance. (Abstract J-101.) Similar results were found in a Brazilian study that compared itraconazole capsules to placebo. (Abstract J-102.)

The bioavailability of ciprofloxacin is significantly decreased in the presence of chemotherapy associated mucositis. (Abstract A-102.)

"Low-risk" febrile neutropenic patients are being managed as outpatients with increasing frequency. Three hundred fifty-five febrile cancer patients with an expected duration of granulocytopenia of less than 10 days were randomized to receive empiric therapy with either ciprofloxacin + amoxicillin-clavulanate (both given po) or ceftriaxone + amikacin (both given IV). The success rates were, respectively, 86% and 84%. (Abstract MN-18.)

Fungal infection is one of the most dreaded complications of the immunosuppression associated with organ transplantation. In one series, 11 (0.6%) of 1730 liver transplant recipients developed brain abscesses-all of which were caused by fungi. Six occurring within 30 days were caused by A. fumigatus, one to Mucor spp., and one to Scedosporium apiospermum-all eight early infections were fatal. In contrast, two infections due to Dactylaria gallopava and one due to C. neoformans, occurred a median of 570 days post-transplantation and were not fatal. Eight (73%) of the 11 patients had simultaneous pulmonary involvement due to the same organism. (Abstract J-99.)